Hematology Times

In an international survey, most oncologists said they would recommend cytotoxic chemotherapy, immune checkpoint inhibitors, and steroids less often during the COVID-19 pandemic.

While neoadjuvant treatment recommendations were not strongly affected by the pandemic, about half of oncologists reported increased hesitancy over recommending frontline chemotherapy for metastatic disease, and a vast majority said they would recommend second- or third-line chemotherapy less often in the metastatic setting.

Most oncologists said they did not perform routine COVID-19 testing via reverse transcriptase–polymerase chain reaction (RT-PCR) before treating cancer patients. In fact, only 3% said they performed COVID-19 RT-PCR testing routinely.

Yüksel Ürün, MD, of Ankara (Turkey) University, and colleagues reported these findings in JCO Global Oncology.

The goal of the survey was to “understand readiness measures taken by oncologists to protect patients and health care workers from the novel coronavirus (COVID-19) and how their clinical decision-making was influenced by the pandemic,” the authors wrote.

The online survey was conducted among 343 oncologists from 28 countries. Responses were collected anonymously, a majority (71%) from university or academic centers, with 95% received between April 1 and April 29, 2020.

Use of telemedicine was common (80%) among respondents, as was use of surgical masks (90%) and personal protective equipment in general.

Only 33% of respondents described using N95 masks. However, the proportion of oncologists who had access to N95 masks while caring for patients known to have COVID-19, especially while doing invasive procedures such as intubation, bronchoscopy, and any airway-related manipulations, was not captured by the survey.
 

COVID testing and cancer treatment

Most respondents (58%) said they did not perform routine COVID-19 RT-PCR testing prior to administering systemic cancer treatment, with 39% stating they performed RT-PCR tests in selected patients, and 3% saying they performed such testing in all patients.

The survey indicated that hormonal treatments, tyrosine kinase inhibitors, and bone-modifying agents were considered relatively safe, but cytotoxic chemotherapy and immune therapies were not.

Nearly all oncologists said the pandemic would cause them to make no change to their recommendations regarding hormone therapy, and nearly 80% said they would make no changes regarding tyrosine kinase inhibitors or bone-modifying agents.

However, more than 90% of respondents said they would recommend cytotoxic chemotherapy less often, about 70% said they would recommend corticosteroids less often, and around 50% said they would recommend anti–programmed death-1/PD-ligand 1 or anti–cytotoxic T-lymphocyte–associated protein 4 antibodies less often.

The pandemic made most respondents more reluctant to recommend second- or third-line chemotherapy in the metastatic setting. About 80% and 70% of respondents, respectively, would recommend second- or third-line chemotherapy less often.

However, first-line chemotherapy for metastatic disease, as well as adjuvant and neoadjuvant therapy, were less affected. About 30% of respondents said they would recommend neoadjuvant therapy less often, and 50%-55% would recommend adjuvant therapy or frontline chemotherapy for metastatic disease less often.

Most respondents (78%) said they would use granulocyte colony–stimulating factor (G-CSF) more frequently during the pandemic.

The factors most likely to affect oncologists’ treatment decisions were patient age (81%) and concomitant disease (92%). Additionally, 80% of respondents’ treatment decisions were influenced by Eastern Cooperative Oncology Group performance status of 2 or higher, or the presence of chronic obstructive pulmonary disease.

Interpretation and implications

“These results highlight that, even in the early phases of COVID-19 – during which there was considerable uncertainty – basic core principles were guideposts for oncologists,” observed Aly-Khan Lalani, MD, of Juravinski Cancer Centre and McMaster University, Hamilton, Ont., who was not involved in this study.

“For example, [oncologists were] prioritizing strategies for treatments with the largest expected impact and carefully tailoring treatment according to patient comorbidities and performance status,” Dr. Lalani said.

Another oncologist who was not involved in the study expressed concern over reductions in adjuvant therapy supported by half of oncologists surveyed.

“Although benefits may be marginal in some cases, these are curative settings and especially warrant careful individual-level risk/benefit discussions,” said Kartik Sehgal, MD, of Dana-Farber Cancer Institute/Brigham and Women’s Hospital in Boston.

His concern extended as well to the small proportion (3%) of oncologists testing for COVID-19 in all patients. “Systematic testing is the need of the hour,” Dr. Sehgal said.

In their discussion of the findings, Dr. Ürün and colleagues noted a lack of consensus on monoclonal antibody and immunotherapy safety among surveyed oncologists. The steroids needed to manage severe immune-mediated toxicity with immune checkpoint inhibitors has led to some prescribing reluctance during the pandemic.

Immunosuppressive properties of immune checkpoint inhibitors also raise concern that they can increase COVID-19 severity. Studies are few, and findings to date are inconsistent with respect to the effect of immune checkpoint inhibitors on COVID-19 clinical course. However, a recently presented study suggested that immune checkpoint inhibitors do not increase the risk of death among cancer patients with COVID-19 (AACR: COVID-19 and Cancer, Abstract S02-01).

Dr. Ürün and colleagues noted that greater COVID-19 severity has been shown in patients with performance status greater than 1, hematologic malignancies, lung cancer, stage IV metastatic disease, chemotherapy within the prior 3 months, cancer treatment in the last 14 days, and the presence of chronic obstructive pulmonary disease. Nonmetastatic cancer has not been shown to affect COVID-19 severity, however.

Dr. Ürün and colleagues also underscored the need for research evidence to balance potential reductions in neutropenic complications with G-CSF (and therefore, reduced hospitalizations) with a theoretical risk of G-CSF–mediated pulmonary injury through its stimulation of an excessive immune response.

Finally, the authors urged oncologists to evaluate each proposed therapy’s risk/benefit ratio on an individual patient basis, and the team tasked the oncology community with gathering comprehensive, rigorous data.

There was no funding source declared for this study. Dr. Ürün and colleagues disclosed various relationships with many pharmaceutical companies, which included receiving research funding. Dr. Sehgal and Dr. Lalani reported no relevant conflicts.
 

SOURCE: Ürün Y et al. JCO Glob Oncol. 2020 Aug;6:1248-57.

In an international survey, most oncologists said they would recommend cytotoxic chemotherapy, immune checkpoint inhibitors, and steroids less often during the COVID-19 pandemic.

While neoadjuvant treatment recommendations were not strongly affected by the pandemic, about half of oncologists reported increased hesitancy over recommending frontline chemotherapy for metastatic disease, and a vast majority said they would recommend second- or third-line chemotherapy less often in the metastatic setting.

Most oncologists said they did not perform routine COVID-19 testing via reverse transcriptase–polymerase chain reaction (RT-PCR) before treating cancer patients. In fact, only 3% said they performed COVID-19 RT-PCR testing routinely.

Yüksel Ürün, MD, of Ankara (Turkey) University, and colleagues reported these findings in JCO Global Oncology.

The goal of the survey was to “understand readiness measures taken by oncologists to protect patients and health care workers from the novel coronavirus (COVID-19) and how their clinical decision-making was influenced by the pandemic,” the authors wrote.

The online survey was conducted among 343 oncologists from 28 countries. Responses were collected anonymously, a majority (71%) from university or academic centers, with 95% received between April 1 and April 29, 2020.

Use of telemedicine was common (80%) among respondents, as was use of surgical masks (90%) and personal protective equipment in general.

Only 33% of respondents described using N95 masks. However, the proportion of oncologists who had access to N95 masks while caring for patients known to have COVID-19, especially while doing invasive procedures such as intubation, bronchoscopy, and any airway-related manipulations, was not captured by the survey.
 

COVID testing and cancer treatment

Most respondents (58%) said they did not perform routine COVID-19 RT-PCR testing prior to administering systemic cancer treatment, with 39% stating they performed RT-PCR tests in selected patients, and 3% saying they performed such testing in all patients.

The survey indicated that hormonal treatments, tyrosine kinase inhibitors, and bone-modifying agents were considered relatively safe, but cytotoxic chemotherapy and immune therapies were not.

Nearly all oncologists said the pandemic would cause them to make no change to their recommendations regarding hormone therapy, and nearly 80% said they would make no changes regarding tyrosine kinase inhibitors or bone-modifying agents.

However, more than 90% of respondents said they would recommend cytotoxic chemotherapy less often, about 70% said they would recommend corticosteroids less often, and around 50% said they would recommend anti–programmed death-1/PD-ligand 1 or anti–cytotoxic T-lymphocyte–associated protein 4 antibodies less often.

The pandemic made most respondents more reluctant to recommend second- or third-line chemotherapy in the metastatic setting. About 80% and 70% of respondents, respectively, would recommend second- or third-line chemotherapy less often.

However, first-line chemotherapy for metastatic disease, as well as adjuvant and neoadjuvant therapy, were less affected. About 30% of respondents said they would recommend neoadjuvant therapy less often, and 50%-55% would recommend adjuvant therapy or frontline chemotherapy for metastatic disease less often.

Most respondents (78%) said they would use granulocyte colony–stimulating factor (G-CSF) more frequently during the pandemic.

The factors most likely to affect oncologists’ treatment decisions were patient age (81%) and concomitant disease (92%). Additionally, 80% of respondents’ treatment decisions were influenced by Eastern Cooperative Oncology Group performance status of 2 or higher, or the presence of chronic obstructive pulmonary disease.

Interpretation and implications

“These results highlight that, even in the early phases of COVID-19 – during which there was considerable uncertainty – basic core principles were guideposts for oncologists,” observed Aly-Khan Lalani, MD, of Juravinski Cancer Centre and McMaster University, Hamilton, Ont., who was not involved in this study.

“For example, [oncologists were] prioritizing strategies for treatments with the largest expected impact and carefully tailoring treatment according to patient comorbidities and performance status,” Dr. Lalani said.

Another oncologist who was not involved in the study expressed concern over reductions in adjuvant therapy supported by half of oncologists surveyed.

“Although benefits may be marginal in some cases, these are curative settings and especially warrant careful individual-level risk/benefit discussions,” said Kartik Sehgal, MD, of Dana-Farber Cancer Institute/Brigham and Women’s Hospital in Boston.

His concern extended as well to the small proportion (3%) of oncologists testing for COVID-19 in all patients. “Systematic testing is the need of the hour,” Dr. Sehgal said.

In their discussion of the findings, Dr. Ürün and colleagues noted a lack of consensus on monoclonal antibody and immunotherapy safety among surveyed oncologists. The steroids needed to manage severe immune-mediated toxicity with immune checkpoint inhibitors has led to some prescribing reluctance during the pandemic.

Immunosuppressive properties of immune checkpoint inhibitors also raise concern that they can increase COVID-19 severity. Studies are few, and findings to date are inconsistent with respect to the effect of immune checkpoint inhibitors on COVID-19 clinical course. However, a recently presented study suggested that immune checkpoint inhibitors do not increase the risk of death among cancer patients with COVID-19 (AACR: COVID-19 and Cancer, Abstract S02-01).

Dr. Ürün and colleagues noted that greater COVID-19 severity has been shown in patients with performance status greater than 1, hematologic malignancies, lung cancer, stage IV metastatic disease, chemotherapy within the prior 3 months, cancer treatment in the last 14 days, and the presence of chronic obstructive pulmonary disease. Nonmetastatic cancer has not been shown to affect COVID-19 severity, however.

Dr. Ürün and colleagues also underscored the need for research evidence to balance potential reductions in neutropenic complications with G-CSF (and therefore, reduced hospitalizations) with a theoretical risk of G-CSF–mediated pulmonary injury through its stimulation of an excessive immune response.

Finally, the authors urged oncologists to evaluate each proposed therapy’s risk/benefit ratio on an individual patient basis, and the team tasked the oncology community with gathering comprehensive, rigorous data.

There was no funding source declared for this study. Dr. Ürün and colleagues disclosed various relationships with many pharmaceutical companies, which included receiving research funding. Dr. Sehgal and Dr. Lalani reported no relevant conflicts.
 

SOURCE: Ürün Y et al. JCO Glob Oncol. 2020 Aug;6:1248-57.

In an international survey, most oncologists said they would recommend cytotoxic chemotherapy, immune checkpoint inhibitors, and steroids less often during the COVID-19 pandemic.

While neoadjuvant treatment recommendations were not strongly affected by the pandemic, about half of oncologists reported increased hesitancy over recommending frontline chemotherapy for metastatic disease, and a vast majority said they would recommend second- or third-line chemotherapy less often in the metastatic setting.

Most oncologists said they did not perform routine COVID-19 testing via reverse transcriptase–polymerase chain reaction (RT-PCR) before treating cancer patients. In fact, only 3% said they performed COVID-19 RT-PCR testing routinely.

Yüksel Ürün, MD, of Ankara (Turkey) University, and colleagues reported these findings in JCO Global Oncology.

The goal of the survey was to “understand readiness measures taken by oncologists to protect patients and health care workers from the novel coronavirus (COVID-19) and how their clinical decision-making was influenced by the pandemic,” the authors wrote.

The online survey was conducted among 343 oncologists from 28 countries. Responses were collected anonymously, a majority (71%) from university or academic centers, with 95% received between April 1 and April 29, 2020.

Use of telemedicine was common (80%) among respondents, as was use of surgical masks (90%) and personal protective equipment in general.

Only 33% of respondents described using N95 masks. However, the proportion of oncologists who had access to N95 masks while caring for patients known to have COVID-19, especially while doing invasive procedures such as intubation, bronchoscopy, and any airway-related manipulations, was not captured by the survey.
 

COVID testing and cancer treatment

Most respondents (58%) said they did not perform routine COVID-19 RT-PCR testing prior to administering systemic cancer treatment, with 39% stating they performed RT-PCR tests in selected patients, and 3% saying they performed such testing in all patients.

The survey indicated that hormonal treatments, tyrosine kinase inhibitors, and bone-modifying agents were considered relatively safe, but cytotoxic chemotherapy and immune therapies were not.

Nearly all oncologists said the pandemic would cause them to make no change to their recommendations regarding hormone therapy, and nearly 80% said they would make no changes regarding tyrosine kinase inhibitors or bone-modifying agents.

However, more than 90% of respondents said they would recommend cytotoxic chemotherapy less often, about 70% said they would recommend corticosteroids less often, and around 50% said they would recommend anti–programmed death-1/PD-ligand 1 or anti–cytotoxic T-lymphocyte–associated protein 4 antibodies less often.

The pandemic made most respondents more reluctant to recommend second- or third-line chemotherapy in the metastatic setting. About 80% and 70% of respondents, respectively, would recommend second- or third-line chemotherapy less often.

However, first-line chemotherapy for metastatic disease, as well as adjuvant and neoadjuvant therapy, were less affected. About 30% of respondents said they would recommend neoadjuvant therapy less often, and 50%-55% would recommend adjuvant therapy or frontline chemotherapy for metastatic disease less often.

Most respondents (78%) said they would use granulocyte colony–stimulating factor (G-CSF) more frequently during the pandemic.

The factors most likely to affect oncologists’ treatment decisions were patient age (81%) and concomitant disease (92%). Additionally, 80% of respondents’ treatment decisions were influenced by Eastern Cooperative Oncology Group performance status of 2 or higher, or the presence of chronic obstructive pulmonary disease.

Interpretation and implications

“These results highlight that, even in the early phases of COVID-19 – during which there was considerable uncertainty – basic core principles were guideposts for oncologists,” observed Aly-Khan Lalani, MD, of Juravinski Cancer Centre and McMaster University, Hamilton, Ont., who was not involved in this study.

“For example, [oncologists were] prioritizing strategies for treatments with the largest expected impact and carefully tailoring treatment according to patient comorbidities and performance status,” Dr. Lalani said.

Another oncologist who was not involved in the study expressed concern over reductions in adjuvant therapy supported by half of oncologists surveyed.

“Although benefits may be marginal in some cases, these are curative settings and especially warrant careful individual-level risk/benefit discussions,” said Kartik Sehgal, MD, of Dana-Farber Cancer Institute/Brigham and Women’s Hospital in Boston.

His concern extended as well to the small proportion (3%) of oncologists testing for COVID-19 in all patients. “Systematic testing is the need of the hour,” Dr. Sehgal said.

In their discussion of the findings, Dr. Ürün and colleagues noted a lack of consensus on monoclonal antibody and immunotherapy safety among surveyed oncologists. The steroids needed to manage severe immune-mediated toxicity with immune checkpoint inhibitors has led to some prescribing reluctance during the pandemic.

Immunosuppressive properties of immune checkpoint inhibitors also raise concern that they can increase COVID-19 severity. Studies are few, and findings to date are inconsistent with respect to the effect of immune checkpoint inhibitors on COVID-19 clinical course. However, a recently presented study suggested that immune checkpoint inhibitors do not increase the risk of death among cancer patients with COVID-19 (AACR: COVID-19 and Cancer, Abstract S02-01).

Dr. Ürün and colleagues noted that greater COVID-19 severity has been shown in patients with performance status greater than 1, hematologic malignancies, lung cancer, stage IV metastatic disease, chemotherapy within the prior 3 months, cancer treatment in the last 14 days, and the presence of chronic obstructive pulmonary disease. Nonmetastatic cancer has not been shown to affect COVID-19 severity, however.

Dr. Ürün and colleagues also underscored the need for research evidence to balance potential reductions in neutropenic complications with G-CSF (and therefore, reduced hospitalizations) with a theoretical risk of G-CSF–mediated pulmonary injury through its stimulation of an excessive immune response.

Finally, the authors urged oncologists to evaluate each proposed therapy’s risk/benefit ratio on an individual patient basis, and the team tasked the oncology community with gathering comprehensive, rigorous data.

There was no funding source declared for this study. Dr. Ürün and colleagues disclosed various relationships with many pharmaceutical companies, which included receiving research funding. Dr. Sehgal and Dr. Lalani reported no relevant conflicts.
 

SOURCE: Ürün Y et al. JCO Glob Oncol. 2020 Aug;6:1248-57.

While SARS-CoV-2 causes frequent and potentially severe pulmonary disease, extrapulmonary manifestations may be a prominent part of the clinical spectrum, according to a review published in Nature Medicine.

In this comprehensive literature review, Aakriti Gupta, MD, of New York-Presbyterian/Columbia University Irving Medical Center and colleagues detailed the epidemiologic and clinical multisystem effects of COVID-19. The authors explained what is known and/or suspected about the pathophysiology of those effects and outlined the resultant management considerations.

Key mechanisms for multiorgan injury include direct viral toxicity, endothelial cell damage with inflammatory mediation of thrombosis, aberrant immune response, and dysregulation of the renin-angiotensin-aldosterone system.

The relative importance of each pathway in the clinical presentation of COVID-19 and the mechanism for extrapulmonary spread of SARS-CoV-2 infection are imperfectly understood, Dr. Gupta and colleagues noted.

As for the hematologic effects of COVID-19, patients may present with several laboratory abnormalities, but the most clinically relevant complications are thromboembolic.
 

COVID-19-associated coagulopathy

Dr. Gupta and colleagues noted that COVID-19–associated coagulopathy (CAC) is accompanied by elevated levels of D-dimer and fibrinogen, with minor abnormalities in prothrombin time, activated partial thromboplastin time, and platelet counts in the initial stage of infection.

Elevated D-dimer levels have been reported in up to 46% of hospitalized patients, and a longitudinal increase while hospitalized is associated with higher mortality.

In initial reports from China and the Netherlands, thrombotic complications were seen in up to 30% of COVID-19 patients in ICUs. Thromboembolic events have been reported in 17%-22% of critically ill COVID-19 patients in studies from Italy and France.

Globally, in severely affected COVID-19 patients, there have been reports of thromboses in intravenous catheters and extracorporeal circuits as well as arterial vascular occlusive events, including myocardial infarction, acute limb ischemia, and stroke.

There have been multiple small studies in which critically ill COVID-19 patients were routinely screened for thrombotic disease. In these studies, rates of thrombotic complications ranged from 69% to 85%, despite thromboprophylaxis. Variability in prophylactic and screening protocols explain discrepancies in event rates.
 

Pathophysiology

The abnormally high blood levels of D-dimer and fibrinogen during the early stages of SARS-CoV-2 infection are reflective of excessive inflammation rather than overt disseminated intravascular coagulation (DIC), which may develop in later stages of illness, according to Dr. Gupta and colleagues. The authors theorized that uninhibited inflammation, along with hypoxia and direct viral-mediated cellular injury, contribute to thrombotic complications in COVID-19 patients.

“The increased expression of ACE2 in endothelial cells after infection with SARS-CoV-2 may perpetuate a vicious cycle of endothelialitis that promotes thromboinflammation,” the authors wrote. “Collectively, hemostatic and inflammatory changes, which reflect endothelial damage and activation as well as critical illness, constitute a prothrombotic milieu.”

The authors noted that small autopsy series have shown high rates of microvascular and macrovascular thromboses, particularly in the pulmonary circulation, in COVID-19 patients.
 

Management considerations

Dr. Gupta and colleagues referenced interim guidelines from the International Society of Thrombosis and Haemostasis that recommend serial complete blood counts, with white blood cell differential and assessment of D-dimer, prothrombin time, and fibrinogen for hospitalized patients with COVID-19. The authors also cited guidelines published in the Journal of the American College of Cardiology that recommend routine risk assessment for venous thromboembolism in all hospitalized patients with COVID-19 and the consideration of standard-dose pharmaco-prophylaxis in patients who lack absolute contraindications.

Empiric use of higher-than-routine prophylactic-dose or therapeutic-dose anticoagulation in ICU patients in the absence of proven thromboses has been implemented in some institutions, Dr. Gupta and colleagues noted. Parenteral anticoagulants (such as low-molecular-weight or unfractionated heparin) are preferred to oral anticoagulants because of short half-life, available reversal agents, and the potential for drug interactions between oral agents and antiviral and/or antibacterial treatment, according to the authors.

They wrote that randomized clinical trials “will be crucial to establishing effective and safe strategies” for anticoagulation in COVID-19 patients. To this point, few randomized trials have been published to guide management of COVID-19–associated extrapulmonary manifestations, including CAC.
 

Research priorities

A more complete understanding of the organ-specific pathophysiology of this multisystem disease is vital, according to Dr. Gupta and colleagues.

“Regional, national, and international collaborations of clinicians and scientists focused on high-quality, transparent, ethical, and evidence-based research practices would help propel the global community toward achieving success against this pandemic,” the authors wrote.

They noted that common definitions and data standards for research are key for cross-institutional and international collaborations.

Initial attention to high-quality prospective scientific documentation standards would have been valuable and will be required for dedicated trials to address the multisystem effects of COVID-19.
 

Community of learners

As much as at any prior time in their careers, during the COVID-19 pandemic, health care providers have been enveloped in a community of learners – a group of people who share values and beliefs and who actively engage in learning from one another.

Through a patchwork of sources – news media, social media, traditional medical journals, general and COVID-focused meetings, and, most importantly, patients – we have been living in a learning-centered environment. Academicians, clinicians, practicing physicians, researchers, patients, family members, and caregivers have been actively and intentionally building a knowledge base together.

Through their published review, Dr. Gupta and colleagues have contributed meaningfully to the understanding our learning community has of the various extrapulmonary manifestations of COVID-19. The authors have provided a nice template for further research and clinical advances.

Dr. Gupta and colleagues disclosed financial relationships with a range of pharmaceutical companies and other organizations.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Source: Gupta A et al. Nat Med. 2020 Jul;26(7):1017-32.

While SARS-CoV-2 causes frequent and potentially severe pulmonary disease, extrapulmonary manifestations may be a prominent part of the clinical spectrum, according to a review published in Nature Medicine.

In this comprehensive literature review, Aakriti Gupta, MD, of New York-Presbyterian/Columbia University Irving Medical Center and colleagues detailed the epidemiologic and clinical multisystem effects of COVID-19. The authors explained what is known and/or suspected about the pathophysiology of those effects and outlined the resultant management considerations.

Key mechanisms for multiorgan injury include direct viral toxicity, endothelial cell damage with inflammatory mediation of thrombosis, aberrant immune response, and dysregulation of the renin-angiotensin-aldosterone system.

The relative importance of each pathway in the clinical presentation of COVID-19 and the mechanism for extrapulmonary spread of SARS-CoV-2 infection are imperfectly understood, Dr. Gupta and colleagues noted.

As for the hematologic effects of COVID-19, patients may present with several laboratory abnormalities, but the most clinically relevant complications are thromboembolic.
 

COVID-19-associated coagulopathy

Dr. Gupta and colleagues noted that COVID-19–associated coagulopathy (CAC) is accompanied by elevated levels of D-dimer and fibrinogen, with minor abnormalities in prothrombin time, activated partial thromboplastin time, and platelet counts in the initial stage of infection.

Elevated D-dimer levels have been reported in up to 46% of hospitalized patients, and a longitudinal increase while hospitalized is associated with higher mortality.

In initial reports from China and the Netherlands, thrombotic complications were seen in up to 30% of COVID-19 patients in ICUs. Thromboembolic events have been reported in 17%-22% of critically ill COVID-19 patients in studies from Italy and France.

Globally, in severely affected COVID-19 patients, there have been reports of thromboses in intravenous catheters and extracorporeal circuits as well as arterial vascular occlusive events, including myocardial infarction, acute limb ischemia, and stroke.

There have been multiple small studies in which critically ill COVID-19 patients were routinely screened for thrombotic disease. In these studies, rates of thrombotic complications ranged from 69% to 85%, despite thromboprophylaxis. Variability in prophylactic and screening protocols explain discrepancies in event rates.
 

Pathophysiology

The abnormally high blood levels of D-dimer and fibrinogen during the early stages of SARS-CoV-2 infection are reflective of excessive inflammation rather than overt disseminated intravascular coagulation (DIC), which may develop in later stages of illness, according to Dr. Gupta and colleagues. The authors theorized that uninhibited inflammation, along with hypoxia and direct viral-mediated cellular injury, contribute to thrombotic complications in COVID-19 patients.

“The increased expression of ACE2 in endothelial cells after infection with SARS-CoV-2 may perpetuate a vicious cycle of endothelialitis that promotes thromboinflammation,” the authors wrote. “Collectively, hemostatic and inflammatory changes, which reflect endothelial damage and activation as well as critical illness, constitute a prothrombotic milieu.”

The authors noted that small autopsy series have shown high rates of microvascular and macrovascular thromboses, particularly in the pulmonary circulation, in COVID-19 patients.
 

Management considerations

Dr. Gupta and colleagues referenced interim guidelines from the International Society of Thrombosis and Haemostasis that recommend serial complete blood counts, with white blood cell differential and assessment of D-dimer, prothrombin time, and fibrinogen for hospitalized patients with COVID-19. The authors also cited guidelines published in the Journal of the American College of Cardiology that recommend routine risk assessment for venous thromboembolism in all hospitalized patients with COVID-19 and the consideration of standard-dose pharmaco-prophylaxis in patients who lack absolute contraindications.

Empiric use of higher-than-routine prophylactic-dose or therapeutic-dose anticoagulation in ICU patients in the absence of proven thromboses has been implemented in some institutions, Dr. Gupta and colleagues noted. Parenteral anticoagulants (such as low-molecular-weight or unfractionated heparin) are preferred to oral anticoagulants because of short half-life, available reversal agents, and the potential for drug interactions between oral agents and antiviral and/or antibacterial treatment, according to the authors.

They wrote that randomized clinical trials “will be crucial to establishing effective and safe strategies” for anticoagulation in COVID-19 patients. To this point, few randomized trials have been published to guide management of COVID-19–associated extrapulmonary manifestations, including CAC.
 

Research priorities

A more complete understanding of the organ-specific pathophysiology of this multisystem disease is vital, according to Dr. Gupta and colleagues.

“Regional, national, and international collaborations of clinicians and scientists focused on high-quality, transparent, ethical, and evidence-based research practices would help propel the global community toward achieving success against this pandemic,” the authors wrote.

They noted that common definitions and data standards for research are key for cross-institutional and international collaborations.

Initial attention to high-quality prospective scientific documentation standards would have been valuable and will be required for dedicated trials to address the multisystem effects of COVID-19.
 

Community of learners

As much as at any prior time in their careers, during the COVID-19 pandemic, health care providers have been enveloped in a community of learners – a group of people who share values and beliefs and who actively engage in learning from one another.

Through a patchwork of sources – news media, social media, traditional medical journals, general and COVID-focused meetings, and, most importantly, patients – we have been living in a learning-centered environment. Academicians, clinicians, practicing physicians, researchers, patients, family members, and caregivers have been actively and intentionally building a knowledge base together.

Through their published review, Dr. Gupta and colleagues have contributed meaningfully to the understanding our learning community has of the various extrapulmonary manifestations of COVID-19. The authors have provided a nice template for further research and clinical advances.

Dr. Gupta and colleagues disclosed financial relationships with a range of pharmaceutical companies and other organizations.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Source: Gupta A et al. Nat Med. 2020 Jul;26(7):1017-32.

While SARS-CoV-2 causes frequent and potentially severe pulmonary disease, extrapulmonary manifestations may be a prominent part of the clinical spectrum, according to a review published in Nature Medicine.

In this comprehensive literature review, Aakriti Gupta, MD, of New York-Presbyterian/Columbia University Irving Medical Center and colleagues detailed the epidemiologic and clinical multisystem effects of COVID-19. The authors explained what is known and/or suspected about the pathophysiology of those effects and outlined the resultant management considerations.

Key mechanisms for multiorgan injury include direct viral toxicity, endothelial cell damage with inflammatory mediation of thrombosis, aberrant immune response, and dysregulation of the renin-angiotensin-aldosterone system.

The relative importance of each pathway in the clinical presentation of COVID-19 and the mechanism for extrapulmonary spread of SARS-CoV-2 infection are imperfectly understood, Dr. Gupta and colleagues noted.

As for the hematologic effects of COVID-19, patients may present with several laboratory abnormalities, but the most clinically relevant complications are thromboembolic.
 

COVID-19-associated coagulopathy

Dr. Gupta and colleagues noted that COVID-19–associated coagulopathy (CAC) is accompanied by elevated levels of D-dimer and fibrinogen, with minor abnormalities in prothrombin time, activated partial thromboplastin time, and platelet counts in the initial stage of infection.

Elevated D-dimer levels have been reported in up to 46% of hospitalized patients, and a longitudinal increase while hospitalized is associated with higher mortality.

In initial reports from China and the Netherlands, thrombotic complications were seen in up to 30% of COVID-19 patients in ICUs. Thromboembolic events have been reported in 17%-22% of critically ill COVID-19 patients in studies from Italy and France.

Globally, in severely affected COVID-19 patients, there have been reports of thromboses in intravenous catheters and extracorporeal circuits as well as arterial vascular occlusive events, including myocardial infarction, acute limb ischemia, and stroke.

There have been multiple small studies in which critically ill COVID-19 patients were routinely screened for thrombotic disease. In these studies, rates of thrombotic complications ranged from 69% to 85%, despite thromboprophylaxis. Variability in prophylactic and screening protocols explain discrepancies in event rates.
 

Pathophysiology

The abnormally high blood levels of D-dimer and fibrinogen during the early stages of SARS-CoV-2 infection are reflective of excessive inflammation rather than overt disseminated intravascular coagulation (DIC), which may develop in later stages of illness, according to Dr. Gupta and colleagues. The authors theorized that uninhibited inflammation, along with hypoxia and direct viral-mediated cellular injury, contribute to thrombotic complications in COVID-19 patients.

“The increased expression of ACE2 in endothelial cells after infection with SARS-CoV-2 may perpetuate a vicious cycle of endothelialitis that promotes thromboinflammation,” the authors wrote. “Collectively, hemostatic and inflammatory changes, which reflect endothelial damage and activation as well as critical illness, constitute a prothrombotic milieu.”

The authors noted that small autopsy series have shown high rates of microvascular and macrovascular thromboses, particularly in the pulmonary circulation, in COVID-19 patients.
 

Management considerations

Dr. Gupta and colleagues referenced interim guidelines from the International Society of Thrombosis and Haemostasis that recommend serial complete blood counts, with white blood cell differential and assessment of D-dimer, prothrombin time, and fibrinogen for hospitalized patients with COVID-19. The authors also cited guidelines published in the Journal of the American College of Cardiology that recommend routine risk assessment for venous thromboembolism in all hospitalized patients with COVID-19 and the consideration of standard-dose pharmaco-prophylaxis in patients who lack absolute contraindications.

Empiric use of higher-than-routine prophylactic-dose or therapeutic-dose anticoagulation in ICU patients in the absence of proven thromboses has been implemented in some institutions, Dr. Gupta and colleagues noted. Parenteral anticoagulants (such as low-molecular-weight or unfractionated heparin) are preferred to oral anticoagulants because of short half-life, available reversal agents, and the potential for drug interactions between oral agents and antiviral and/or antibacterial treatment, according to the authors.

They wrote that randomized clinical trials “will be crucial to establishing effective and safe strategies” for anticoagulation in COVID-19 patients. To this point, few randomized trials have been published to guide management of COVID-19–associated extrapulmonary manifestations, including CAC.
 

Research priorities

A more complete understanding of the organ-specific pathophysiology of this multisystem disease is vital, according to Dr. Gupta and colleagues.

“Regional, national, and international collaborations of clinicians and scientists focused on high-quality, transparent, ethical, and evidence-based research practices would help propel the global community toward achieving success against this pandemic,” the authors wrote.

They noted that common definitions and data standards for research are key for cross-institutional and international collaborations.

Initial attention to high-quality prospective scientific documentation standards would have been valuable and will be required for dedicated trials to address the multisystem effects of COVID-19.
 

Community of learners

As much as at any prior time in their careers, during the COVID-19 pandemic, health care providers have been enveloped in a community of learners – a group of people who share values and beliefs and who actively engage in learning from one another.

Through a patchwork of sources – news media, social media, traditional medical journals, general and COVID-focused meetings, and, most importantly, patients – we have been living in a learning-centered environment. Academicians, clinicians, practicing physicians, researchers, patients, family members, and caregivers have been actively and intentionally building a knowledge base together.

Through their published review, Dr. Gupta and colleagues have contributed meaningfully to the understanding our learning community has of the various extrapulmonary manifestations of COVID-19. The authors have provided a nice template for further research and clinical advances.

Dr. Gupta and colleagues disclosed financial relationships with a range of pharmaceutical companies and other organizations.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Source: Gupta A et al. Nat Med. 2020 Jul;26(7):1017-32.

The COVID-19 pandemic has disrupted every aspect of cancer care, from diagnosis, treatment, and follow-up to participation in clinical trials, according to a new report that collected responses from cancer patient organizations around the world.

The report includes responses from 157 organizations in 56 countries, representing some 350,000 patients with cancer.

“The COVID-19 global pandemic has quite literally wreaked havoc with all of our lives but especially for cancer patients,” said the report’s author, Frances Reid, MBA, program director, World Ovarian Cancer Coalition.

“To those who have the power or influence to ensure that cancer treatment and services are not set back several years, please listen to those organizations who can articulate clearly the impact on patients, work with them, and act on it as soon as you can,” she added.

The new report, entitled “The Impact of COVID-19 on Cancer Patient Organisations,” was released on June 12. The organizations were surveyed from May 11 to May 25.
 

Cancer diagnosis

Two-thirds of the organizations surveyed said cancer screening programs had been canceled in their country, and 59% indicated they had seen a drop in urgent referrals for suspected cancer.

Some 44% said that access to pathology services had been reduced. One group in Australia reported that “results of pathology tests are taking longer to be returned. Generally a result would be returned within 48 hours. Since COVID-19, results are taking up to 7 days to be returned.”

As for treatment, 68% of organizations reported delays or cancellations of surgery or other treatments; 58% reported there had been a need to modify treatment protocols; and 48% indicated there had been a drop in participation in clinical trials.

Respondents were also concerned about reported increases in stress, anxiety, and isolation among many cancer patients. “Often at increased risk of infection and serious illness themselves ... many have been required to ‘shield’ from others, totally withdrawing from life outside their homes, thus increasing the already high levels of isolation they feel because of their life-limiting conditions,” the report notes.

In addition, some 60% of the organizations said that the pandemic had increased financial hardship among cancer patients. One US group commented: “Unemployment levels in the States similar to depression era. This has been a real challenge as many have lost insurance as well as jobs.”

Only a minority of respondents reported that cancer care was being offered in hospitals with no special arrangements in place to treat concomitant COVID-19 patients.

On the other hand, only 15% of respondents indicated that patients were being treated in a hospital that was not also caring for COVID-19 patients.

“Cancer will not wait for COVID-19 to pass, if it ever will, and the patient organizations are the key to minimizing the devastating impact [COVID-19 is having] on people with cancer,” Reid emphasized.

“More than ever, the patient/support services should be strengthened,” commented a group from France.
 

Patient services affected

“Almost all organisations (89%) have had to alter their services for people with cancer,” the report notes.

Two thirds of organizations involved in professional educational activities have had to change their services in some way, either by moving them online or stopping programs altogether, at least temporarily. “Some found that doctors and nurses are too busy with the pandemic to participate, and that their appetite for such activity is also diminished,” the report notes.

The volume of phone calls and emails increased in almost 6 of 10 organizations that provide support services for patients. Compared to prepandemic levels, volume increased by an average of 44%.

The most common queries raised by people with cancer (accounting for 85% of all queries) were questions about the risks of contracting COVID-19 and cancer treatments during the pandemic.

Some of the organizations also commented about how they had been affected. One group from Uganda said: “We had a sudden lockdown and we could not access office to give face to face counselling. We stopped research due to national guidelines on research. We continued giving information via phone and social media especially WhatsApp. We created groups for patients and counsellors to continue interacting.”

A group in Costa Rica reported: “We developed a new program of transfers from their homes to the hospital for cancer patients in chemotherapy and radiotherapy. 200 monthly transfers. We created a virtual community instead of our face-to-face support group, we started in April and we have 108 members, virtual sessions are held every two weeks.”

An organization based in the United States reported that it was “totally revamping our educational programs to be delivered in new ways in an online format ― not just replicating the in-person formats, but reaching out to our community and asking them what they would find the most valuable.”
 

Impact on fundraising

Almost 9 in 10 organizations raise funds to support their activities, the report notes. “A shocking 79% of organisations say they predict a fall in income over the next 12 months, with a further 16% not sure, leaving only 5% confident of their financial stability.”

Every type of fund-raising has been affected by COVID-19, from grants and major donors to community fund-raising events. Sixty percent of organisations said they were trying to find new ways to raise funds.

However, as one organization in Japan noted: “At the moment we can survive and feel it is unethical to ask the public for money when many are facing dire financial personal circumstances.”

A group from Australia commented: “Fundraising has been extremely difficult due to COVID-19 with distancing laws and no group gatherings as well as the economic downturn. Crisis appeals have been unsuccessful and all outdoor events and major events have been cancelled. In Australia we have had to contend with also the fires earlier in the year where a lot of money was donated to leaving other foundations struggling to get donor support.”

A little more than half (55%) of the organizations surveyed have had to cut costs.

Staffing cuts have been made in 1 in 10 of the organizations surveyed. A similar proportion of organizations have furloughed staff. Many if not all staff from numerous organizations are working from home.

A little more than half of those surveyed either provide funding for research or conduct research themselves, but only one quarter of them indicated there had been no change in their research projects. The others have indicated that they had to either reduce the scope of their research, put it on pause, or stop it altogether.

Three quarters of survey respondents noted that they had engaged in advocacy activities prior to the pandemic, and almost two thirds of them said they had to delay these activities.

Several of the organizations expressed thanks to the survey authors.

“COVID-19 is a global pandemic and cancer patients all around the world have similar worries, concerns and questions ― we are a small/medium organisation working in one country but believe in the power of community and coalitions and so this survey is a very welcome part of looking at this from a greater perspective,” commented one British group.

Reid has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The COVID-19 pandemic has disrupted every aspect of cancer care, from diagnosis, treatment, and follow-up to participation in clinical trials, according to a new report that collected responses from cancer patient organizations around the world.

The report includes responses from 157 organizations in 56 countries, representing some 350,000 patients with cancer.

“The COVID-19 global pandemic has quite literally wreaked havoc with all of our lives but especially for cancer patients,” said the report’s author, Frances Reid, MBA, program director, World Ovarian Cancer Coalition.

“To those who have the power or influence to ensure that cancer treatment and services are not set back several years, please listen to those organizations who can articulate clearly the impact on patients, work with them, and act on it as soon as you can,” she added.

The new report, entitled “The Impact of COVID-19 on Cancer Patient Organisations,” was released on June 12. The organizations were surveyed from May 11 to May 25.
 

Cancer diagnosis

Two-thirds of the organizations surveyed said cancer screening programs had been canceled in their country, and 59% indicated they had seen a drop in urgent referrals for suspected cancer.

Some 44% said that access to pathology services had been reduced. One group in Australia reported that “results of pathology tests are taking longer to be returned. Generally a result would be returned within 48 hours. Since COVID-19, results are taking up to 7 days to be returned.”

As for treatment, 68% of organizations reported delays or cancellations of surgery or other treatments; 58% reported there had been a need to modify treatment protocols; and 48% indicated there had been a drop in participation in clinical trials.

Respondents were also concerned about reported increases in stress, anxiety, and isolation among many cancer patients. “Often at increased risk of infection and serious illness themselves ... many have been required to ‘shield’ from others, totally withdrawing from life outside their homes, thus increasing the already high levels of isolation they feel because of their life-limiting conditions,” the report notes.

In addition, some 60% of the organizations said that the pandemic had increased financial hardship among cancer patients. One US group commented: “Unemployment levels in the States similar to depression era. This has been a real challenge as many have lost insurance as well as jobs.”

Only a minority of respondents reported that cancer care was being offered in hospitals with no special arrangements in place to treat concomitant COVID-19 patients.

On the other hand, only 15% of respondents indicated that patients were being treated in a hospital that was not also caring for COVID-19 patients.

“Cancer will not wait for COVID-19 to pass, if it ever will, and the patient organizations are the key to minimizing the devastating impact [COVID-19 is having] on people with cancer,” Reid emphasized.

“More than ever, the patient/support services should be strengthened,” commented a group from France.
 

Patient services affected

“Almost all organisations (89%) have had to alter their services for people with cancer,” the report notes.

Two thirds of organizations involved in professional educational activities have had to change their services in some way, either by moving them online or stopping programs altogether, at least temporarily. “Some found that doctors and nurses are too busy with the pandemic to participate, and that their appetite for such activity is also diminished,” the report notes.

The volume of phone calls and emails increased in almost 6 of 10 organizations that provide support services for patients. Compared to prepandemic levels, volume increased by an average of 44%.

The most common queries raised by people with cancer (accounting for 85% of all queries) were questions about the risks of contracting COVID-19 and cancer treatments during the pandemic.

Some of the organizations also commented about how they had been affected. One group from Uganda said: “We had a sudden lockdown and we could not access office to give face to face counselling. We stopped research due to national guidelines on research. We continued giving information via phone and social media especially WhatsApp. We created groups for patients and counsellors to continue interacting.”

A group in Costa Rica reported: “We developed a new program of transfers from their homes to the hospital for cancer patients in chemotherapy and radiotherapy. 200 monthly transfers. We created a virtual community instead of our face-to-face support group, we started in April and we have 108 members, virtual sessions are held every two weeks.”

An organization based in the United States reported that it was “totally revamping our educational programs to be delivered in new ways in an online format ― not just replicating the in-person formats, but reaching out to our community and asking them what they would find the most valuable.”
 

Impact on fundraising

Almost 9 in 10 organizations raise funds to support their activities, the report notes. “A shocking 79% of organisations say they predict a fall in income over the next 12 months, with a further 16% not sure, leaving only 5% confident of their financial stability.”

Every type of fund-raising has been affected by COVID-19, from grants and major donors to community fund-raising events. Sixty percent of organisations said they were trying to find new ways to raise funds.

However, as one organization in Japan noted: “At the moment we can survive and feel it is unethical to ask the public for money when many are facing dire financial personal circumstances.”

A group from Australia commented: “Fundraising has been extremely difficult due to COVID-19 with distancing laws and no group gatherings as well as the economic downturn. Crisis appeals have been unsuccessful and all outdoor events and major events have been cancelled. In Australia we have had to contend with also the fires earlier in the year where a lot of money was donated to leaving other foundations struggling to get donor support.”

A little more than half (55%) of the organizations surveyed have had to cut costs.

Staffing cuts have been made in 1 in 10 of the organizations surveyed. A similar proportion of organizations have furloughed staff. Many if not all staff from numerous organizations are working from home.

A little more than half of those surveyed either provide funding for research or conduct research themselves, but only one quarter of them indicated there had been no change in their research projects. The others have indicated that they had to either reduce the scope of their research, put it on pause, or stop it altogether.

Three quarters of survey respondents noted that they had engaged in advocacy activities prior to the pandemic, and almost two thirds of them said they had to delay these activities.

Several of the organizations expressed thanks to the survey authors.

“COVID-19 is a global pandemic and cancer patients all around the world have similar worries, concerns and questions ― we are a small/medium organisation working in one country but believe in the power of community and coalitions and so this survey is a very welcome part of looking at this from a greater perspective,” commented one British group.

Reid has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The COVID-19 pandemic has disrupted every aspect of cancer care, from diagnosis, treatment, and follow-up to participation in clinical trials, according to a new report that collected responses from cancer patient organizations around the world.

The report includes responses from 157 organizations in 56 countries, representing some 350,000 patients with cancer.

“The COVID-19 global pandemic has quite literally wreaked havoc with all of our lives but especially for cancer patients,” said the report’s author, Frances Reid, MBA, program director, World Ovarian Cancer Coalition.

“To those who have the power or influence to ensure that cancer treatment and services are not set back several years, please listen to those organizations who can articulate clearly the impact on patients, work with them, and act on it as soon as you can,” she added.

The new report, entitled “The Impact of COVID-19 on Cancer Patient Organisations,” was released on June 12. The organizations were surveyed from May 11 to May 25.
 

Cancer diagnosis

Two-thirds of the organizations surveyed said cancer screening programs had been canceled in their country, and 59% indicated they had seen a drop in urgent referrals for suspected cancer.

Some 44% said that access to pathology services had been reduced. One group in Australia reported that “results of pathology tests are taking longer to be returned. Generally a result would be returned within 48 hours. Since COVID-19, results are taking up to 7 days to be returned.”

As for treatment, 68% of organizations reported delays or cancellations of surgery or other treatments; 58% reported there had been a need to modify treatment protocols; and 48% indicated there had been a drop in participation in clinical trials.

Respondents were also concerned about reported increases in stress, anxiety, and isolation among many cancer patients. “Often at increased risk of infection and serious illness themselves ... many have been required to ‘shield’ from others, totally withdrawing from life outside their homes, thus increasing the already high levels of isolation they feel because of their life-limiting conditions,” the report notes.

In addition, some 60% of the organizations said that the pandemic had increased financial hardship among cancer patients. One US group commented: “Unemployment levels in the States similar to depression era. This has been a real challenge as many have lost insurance as well as jobs.”

Only a minority of respondents reported that cancer care was being offered in hospitals with no special arrangements in place to treat concomitant COVID-19 patients.

On the other hand, only 15% of respondents indicated that patients were being treated in a hospital that was not also caring for COVID-19 patients.

“Cancer will not wait for COVID-19 to pass, if it ever will, and the patient organizations are the key to minimizing the devastating impact [COVID-19 is having] on people with cancer,” Reid emphasized.

“More than ever, the patient/support services should be strengthened,” commented a group from France.
 

Patient services affected

“Almost all organisations (89%) have had to alter their services for people with cancer,” the report notes.

Two thirds of organizations involved in professional educational activities have had to change their services in some way, either by moving them online or stopping programs altogether, at least temporarily. “Some found that doctors and nurses are too busy with the pandemic to participate, and that their appetite for such activity is also diminished,” the report notes.

The volume of phone calls and emails increased in almost 6 of 10 organizations that provide support services for patients. Compared to prepandemic levels, volume increased by an average of 44%.

The most common queries raised by people with cancer (accounting for 85% of all queries) were questions about the risks of contracting COVID-19 and cancer treatments during the pandemic.

Some of the organizations also commented about how they had been affected. One group from Uganda said: “We had a sudden lockdown and we could not access office to give face to face counselling. We stopped research due to national guidelines on research. We continued giving information via phone and social media especially WhatsApp. We created groups for patients and counsellors to continue interacting.”

A group in Costa Rica reported: “We developed a new program of transfers from their homes to the hospital for cancer patients in chemotherapy and radiotherapy. 200 monthly transfers. We created a virtual community instead of our face-to-face support group, we started in April and we have 108 members, virtual sessions are held every two weeks.”

An organization based in the United States reported that it was “totally revamping our educational programs to be delivered in new ways in an online format ― not just replicating the in-person formats, but reaching out to our community and asking them what they would find the most valuable.”
 

Impact on fundraising

Almost 9 in 10 organizations raise funds to support their activities, the report notes. “A shocking 79% of organisations say they predict a fall in income over the next 12 months, with a further 16% not sure, leaving only 5% confident of their financial stability.”

Every type of fund-raising has been affected by COVID-19, from grants and major donors to community fund-raising events. Sixty percent of organisations said they were trying to find new ways to raise funds.

However, as one organization in Japan noted: “At the moment we can survive and feel it is unethical to ask the public for money when many are facing dire financial personal circumstances.”

A group from Australia commented: “Fundraising has been extremely difficult due to COVID-19 with distancing laws and no group gatherings as well as the economic downturn. Crisis appeals have been unsuccessful and all outdoor events and major events have been cancelled. In Australia we have had to contend with also the fires earlier in the year where a lot of money was donated to leaving other foundations struggling to get donor support.”

A little more than half (55%) of the organizations surveyed have had to cut costs.

Staffing cuts have been made in 1 in 10 of the organizations surveyed. A similar proportion of organizations have furloughed staff. Many if not all staff from numerous organizations are working from home.

A little more than half of those surveyed either provide funding for research or conduct research themselves, but only one quarter of them indicated there had been no change in their research projects. The others have indicated that they had to either reduce the scope of their research, put it on pause, or stop it altogether.

Three quarters of survey respondents noted that they had engaged in advocacy activities prior to the pandemic, and almost two thirds of them said they had to delay these activities.

Several of the organizations expressed thanks to the survey authors.

“COVID-19 is a global pandemic and cancer patients all around the world have similar worries, concerns and questions ― we are a small/medium organisation working in one country but believe in the power of community and coalitions and so this survey is a very welcome part of looking at this from a greater perspective,” commented one British group.

Reid has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has granted accelerated approval of the EZH2 inhibitor tazemetostat (Tazverik, Epizyme, Inc) for the treatment of relapsed or refractory follicular lymphoma in adult patients with tumors harboring an EZH2 mutation.

Eligible patients must have already received at least two prior systemic therapies and have tumors that are positive for an EZH2 mutation, as detected by an FDA-approved test. The FDA has also approved the cobas EZH2 Mutation Test (Roche Molecular Systems, Inc) as a companion diagnostic test for tazemetostat.

The new indication is also for adult patients with relapsed/refractory follicular lymphoma who have no other satisfactory alternative treatment options.

“In our view, there remains no clear standard of care in the relapsed and/or refractory [follicular lymphoma] population, as not all patients benefit from today’s available therapies,” said Shefali Agarwal, MD, chief medical officer of Epizyme, in a company press release. “Based on this label, physicians will have the ability to use their clinical discretion to prescribe tazemetostat for their relapsed or refractory patients regardless of EZH2 mutational status and without regard to a specific line of treatment where other options are not satisfactory.”

This accelerated approval is based on overall response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials, the FDA notes.

Tazemetostat acts as an inhibitor of EZH2 methyltransferase. Earlier this year, the drug was approved for the treatment of metastatic or locally advanced epithelioid sarcoma in cases in which complete resection is not possible. It is the first drug with this mechanism of action and is the first to be indicated for epithelioid sarcoma.

Promising Efficacy in Phase 2 Trial

The new approval for use in follicular lymphoma was based on results from an open-label, single-arm, multicenter phase 2 clinical trial involving patients who had experienced disease progression after being treated with at least two prior systemic regimens. The cohort was divided into two treatment groups: One group consisted of 45 patients with EZH2-activating mutations, the other included 54 patients with wild-type EZH2.

All patients received tazemetostat at 800 mg administered orally twice a day. The primary efficacy outcome measures were overall response rate and duration of response, in accordance with International Working Group Non-Hodgkin Lymphoma criteria.

The median duration of follow-up was 22 months for patients with EZH2-activating mutations and 36 months for those with wild-type tumors.

Among the 45 patients with an EZH2-activating mutation, the median number of lines of prior systemic therapy was 2.0 (range, 1 – 11). In 49% of patients, disease was refractory to rituximab, and in 49%, it was refractory to the patient’s last therapy.

The overall response rate was 69%; 12% of patients achieved a complete response, and 57% achieved a partial response. The median duration of response was 10.9 months and ongoing.

In the cohort of 54 patients with wild-type EZH2, the median number previous therapies was 3.0 (range, 1 – 8); in 59% of patients, disease was refractory to rituximab, and in 41%, it was refractory to the patient’s last therapy.

The overall response rate to tazemetostat treatment was 34%; 4% of patients achieved a complete response, and 30% achieved a partial response. The median duration of response was 13 months.

Serious adverse reactions occurred in 30% of patients. The most common were fatigue, upper respiratory tract infection, musculoskeletal pain, nausea, and abdominal pain. Eight patients (8%) discontinued treatment during the trial because of adverse events. There were no reported deaths. No black box warnings have been published, and there are no contraindications.

“The durable responses observed with this drug are notable in the context of the safety profile and route of oral, at-home administration, and will offer an important new option for physicians as we care for patients with relapsed/refractory follicular lymphoma,” said John Leonard, MD, in a company press release. He is associate dean for clinical research and Richard T. Silver Distinguished Professor of Hematology and Medical Oncology, Meyer Cancer Center, Weill Cornell Medicine and New York–Presbyterian Hospital, New York, and an investigator in the ongoing phase 1b/3 confirmatory trial for tazemetostat.

“Follicular lymphoma remains an incurable disease, and even with the availability of new drugs in recent years, there have remained important unmet needs in the treatment of follicular lymphoma,” he commented.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has granted accelerated approval of the EZH2 inhibitor tazemetostat (Tazverik, Epizyme, Inc) for the treatment of relapsed or refractory follicular lymphoma in adult patients with tumors harboring an EZH2 mutation.

Eligible patients must have already received at least two prior systemic therapies and have tumors that are positive for an EZH2 mutation, as detected by an FDA-approved test. The FDA has also approved the cobas EZH2 Mutation Test (Roche Molecular Systems, Inc) as a companion diagnostic test for tazemetostat.

The new indication is also for adult patients with relapsed/refractory follicular lymphoma who have no other satisfactory alternative treatment options.

“In our view, there remains no clear standard of care in the relapsed and/or refractory [follicular lymphoma] population, as not all patients benefit from today’s available therapies,” said Shefali Agarwal, MD, chief medical officer of Epizyme, in a company press release. “Based on this label, physicians will have the ability to use their clinical discretion to prescribe tazemetostat for their relapsed or refractory patients regardless of EZH2 mutational status and without regard to a specific line of treatment where other options are not satisfactory.”

This accelerated approval is based on overall response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials, the FDA notes.

Tazemetostat acts as an inhibitor of EZH2 methyltransferase. Earlier this year, the drug was approved for the treatment of metastatic or locally advanced epithelioid sarcoma in cases in which complete resection is not possible. It is the first drug with this mechanism of action and is the first to be indicated for epithelioid sarcoma.

Promising Efficacy in Phase 2 Trial

The new approval for use in follicular lymphoma was based on results from an open-label, single-arm, multicenter phase 2 clinical trial involving patients who had experienced disease progression after being treated with at least two prior systemic regimens. The cohort was divided into two treatment groups: One group consisted of 45 patients with EZH2-activating mutations, the other included 54 patients with wild-type EZH2.

All patients received tazemetostat at 800 mg administered orally twice a day. The primary efficacy outcome measures were overall response rate and duration of response, in accordance with International Working Group Non-Hodgkin Lymphoma criteria.

The median duration of follow-up was 22 months for patients with EZH2-activating mutations and 36 months for those with wild-type tumors.

Among the 45 patients with an EZH2-activating mutation, the median number of lines of prior systemic therapy was 2.0 (range, 1 – 11). In 49% of patients, disease was refractory to rituximab, and in 49%, it was refractory to the patient’s last therapy.

The overall response rate was 69%; 12% of patients achieved a complete response, and 57% achieved a partial response. The median duration of response was 10.9 months and ongoing.

In the cohort of 54 patients with wild-type EZH2, the median number previous therapies was 3.0 (range, 1 – 8); in 59% of patients, disease was refractory to rituximab, and in 41%, it was refractory to the patient’s last therapy.

The overall response rate to tazemetostat treatment was 34%; 4% of patients achieved a complete response, and 30% achieved a partial response. The median duration of response was 13 months.

Serious adverse reactions occurred in 30% of patients. The most common were fatigue, upper respiratory tract infection, musculoskeletal pain, nausea, and abdominal pain. Eight patients (8%) discontinued treatment during the trial because of adverse events. There were no reported deaths. No black box warnings have been published, and there are no contraindications.

“The durable responses observed with this drug are notable in the context of the safety profile and route of oral, at-home administration, and will offer an important new option for physicians as we care for patients with relapsed/refractory follicular lymphoma,” said John Leonard, MD, in a company press release. He is associate dean for clinical research and Richard T. Silver Distinguished Professor of Hematology and Medical Oncology, Meyer Cancer Center, Weill Cornell Medicine and New York–Presbyterian Hospital, New York, and an investigator in the ongoing phase 1b/3 confirmatory trial for tazemetostat.

“Follicular lymphoma remains an incurable disease, and even with the availability of new drugs in recent years, there have remained important unmet needs in the treatment of follicular lymphoma,” he commented.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has granted accelerated approval of the EZH2 inhibitor tazemetostat (Tazverik, Epizyme, Inc) for the treatment of relapsed or refractory follicular lymphoma in adult patients with tumors harboring an EZH2 mutation.

Eligible patients must have already received at least two prior systemic therapies and have tumors that are positive for an EZH2 mutation, as detected by an FDA-approved test. The FDA has also approved the cobas EZH2 Mutation Test (Roche Molecular Systems, Inc) as a companion diagnostic test for tazemetostat.

The new indication is also for adult patients with relapsed/refractory follicular lymphoma who have no other satisfactory alternative treatment options.

“In our view, there remains no clear standard of care in the relapsed and/or refractory [follicular lymphoma] population, as not all patients benefit from today’s available therapies,” said Shefali Agarwal, MD, chief medical officer of Epizyme, in a company press release. “Based on this label, physicians will have the ability to use their clinical discretion to prescribe tazemetostat for their relapsed or refractory patients regardless of EZH2 mutational status and without regard to a specific line of treatment where other options are not satisfactory.”

This accelerated approval is based on overall response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials, the FDA notes.

Tazemetostat acts as an inhibitor of EZH2 methyltransferase. Earlier this year, the drug was approved for the treatment of metastatic or locally advanced epithelioid sarcoma in cases in which complete resection is not possible. It is the first drug with this mechanism of action and is the first to be indicated for epithelioid sarcoma.

Promising Efficacy in Phase 2 Trial

The new approval for use in follicular lymphoma was based on results from an open-label, single-arm, multicenter phase 2 clinical trial involving patients who had experienced disease progression after being treated with at least two prior systemic regimens. The cohort was divided into two treatment groups: One group consisted of 45 patients with EZH2-activating mutations, the other included 54 patients with wild-type EZH2.

All patients received tazemetostat at 800 mg administered orally twice a day. The primary efficacy outcome measures were overall response rate and duration of response, in accordance with International Working Group Non-Hodgkin Lymphoma criteria.

The median duration of follow-up was 22 months for patients with EZH2-activating mutations and 36 months for those with wild-type tumors.

Among the 45 patients with an EZH2-activating mutation, the median number of lines of prior systemic therapy was 2.0 (range, 1 – 11). In 49% of patients, disease was refractory to rituximab, and in 49%, it was refractory to the patient’s last therapy.

The overall response rate was 69%; 12% of patients achieved a complete response, and 57% achieved a partial response. The median duration of response was 10.9 months and ongoing.

In the cohort of 54 patients with wild-type EZH2, the median number previous therapies was 3.0 (range, 1 – 8); in 59% of patients, disease was refractory to rituximab, and in 41%, it was refractory to the patient’s last therapy.

The overall response rate to tazemetostat treatment was 34%; 4% of patients achieved a complete response, and 30% achieved a partial response. The median duration of response was 13 months.

Serious adverse reactions occurred in 30% of patients. The most common were fatigue, upper respiratory tract infection, musculoskeletal pain, nausea, and abdominal pain. Eight patients (8%) discontinued treatment during the trial because of adverse events. There were no reported deaths. No black box warnings have been published, and there are no contraindications.

“The durable responses observed with this drug are notable in the context of the safety profile and route of oral, at-home administration, and will offer an important new option for physicians as we care for patients with relapsed/refractory follicular lymphoma,” said John Leonard, MD, in a company press release. He is associate dean for clinical research and Richard T. Silver Distinguished Professor of Hematology and Medical Oncology, Meyer Cancer Center, Weill Cornell Medicine and New York–Presbyterian Hospital, New York, and an investigator in the ongoing phase 1b/3 confirmatory trial for tazemetostat.

“Follicular lymphoma remains an incurable disease, and even with the availability of new drugs in recent years, there have remained important unmet needs in the treatment of follicular lymphoma,” he commented.

This article first appeared on Medscape.com.

One of five physicians in front-line treatment roles has prescribed hydroxychloroquine for COVID-19, according to a new survey from health care market research company InCrowd.

The most common treatments were acetaminophen, prescribed to 82% of patients, antibiotics (41%), and bronchodilators (40%), InCrowd said after surveying 203 primary care physicians, pediatricians, and emergency medicine or critical care physicians who are treating at least 20 patients with flulike symptoms.

On April 24, the Food and Drug Administration warned against the use of hydroxychloroquine or chloroquine outside of hospitals and clinical trials.

The InCrowd survey, which took place April 14-15 and is the fourth in a series investigating COVID-19’s impact on physicians, showed that access to testing was up to 82% in mid-April, compared with 67% in March and 20% in late February. The April respondents also were twice as likely (59% vs. 24% in March) to say that their facilities were prepared to treat patients, InCrowd reported.

“U.S. physicians report sluggish optimism around preparedness, safety, and institutional efforts, while many worry about the future, including a second outbreak and job security,” the company said in a separate written statement.

The average estimate for a return to normal was just over 6 months among respondents, and only 28% believed that their facility was prepared for a second outbreak later in the year, InCrowd noted.

On a personal level, 45% of the respondents were concerned about the safety of their job. An emergency/critical care physician from Tennessee said, “We’ve been cutting back on staff due to overall revenue reductions, but have increased acuity and complexity which requires more staffing. This puts even more of a burden on those of us still here.”

Support for institutional responses to slow the pandemic was strongest for state governments, which gained approval from 54% of front-line physicians, up from 33% in March. Actions taken by the federal government were supported by 21% of respondents, compared with 38% for the World Health Organization and 46% for governments outside the United States, InCrowd reported.

Suggestions for further actions by state and local authorities included this comment from an emergency/critical care physician in Florida: “Continued, broad and properly enforced stay at home and social distancing measures MUST remain in place to keep citizens and healthcare workers safe, and the latter alive and in adequate supply.”

rfranki@mdedge.com

One of five physicians in front-line treatment roles has prescribed hydroxychloroquine for COVID-19, according to a new survey from health care market research company InCrowd.

The most common treatments were acetaminophen, prescribed to 82% of patients, antibiotics (41%), and bronchodilators (40%), InCrowd said after surveying 203 primary care physicians, pediatricians, and emergency medicine or critical care physicians who are treating at least 20 patients with flulike symptoms.

On April 24, the Food and Drug Administration warned against the use of hydroxychloroquine or chloroquine outside of hospitals and clinical trials.

The InCrowd survey, which took place April 14-15 and is the fourth in a series investigating COVID-19’s impact on physicians, showed that access to testing was up to 82% in mid-April, compared with 67% in March and 20% in late February. The April respondents also were twice as likely (59% vs. 24% in March) to say that their facilities were prepared to treat patients, InCrowd reported.

“U.S. physicians report sluggish optimism around preparedness, safety, and institutional efforts, while many worry about the future, including a second outbreak and job security,” the company said in a separate written statement.

The average estimate for a return to normal was just over 6 months among respondents, and only 28% believed that their facility was prepared for a second outbreak later in the year, InCrowd noted.

On a personal level, 45% of the respondents were concerned about the safety of their job. An emergency/critical care physician from Tennessee said, “We’ve been cutting back on staff due to overall revenue reductions, but have increased acuity and complexity which requires more staffing. This puts even more of a burden on those of us still here.”

Support for institutional responses to slow the pandemic was strongest for state governments, which gained approval from 54% of front-line physicians, up from 33% in March. Actions taken by the federal government were supported by 21% of respondents, compared with 38% for the World Health Organization and 46% for governments outside the United States, InCrowd reported.

Suggestions for further actions by state and local authorities included this comment from an emergency/critical care physician in Florida: “Continued, broad and properly enforced stay at home and social distancing measures MUST remain in place to keep citizens and healthcare workers safe, and the latter alive and in adequate supply.”

rfranki@mdedge.com

One of five physicians in front-line treatment roles has prescribed hydroxychloroquine for COVID-19, according to a new survey from health care market research company InCrowd.

The most common treatments were acetaminophen, prescribed to 82% of patients, antibiotics (41%), and bronchodilators (40%), InCrowd said after surveying 203 primary care physicians, pediatricians, and emergency medicine or critical care physicians who are treating at least 20 patients with flulike symptoms.

On April 24, the Food and Drug Administration warned against the use of hydroxychloroquine or chloroquine outside of hospitals and clinical trials.

The InCrowd survey, which took place April 14-15 and is the fourth in a series investigating COVID-19’s impact on physicians, showed that access to testing was up to 82% in mid-April, compared with 67% in March and 20% in late February. The April respondents also were twice as likely (59% vs. 24% in March) to say that their facilities were prepared to treat patients, InCrowd reported.

“U.S. physicians report sluggish optimism around preparedness, safety, and institutional efforts, while many worry about the future, including a second outbreak and job security,” the company said in a separate written statement.

The average estimate for a return to normal was just over 6 months among respondents, and only 28% believed that their facility was prepared for a second outbreak later in the year, InCrowd noted.

On a personal level, 45% of the respondents were concerned about the safety of their job. An emergency/critical care physician from Tennessee said, “We’ve been cutting back on staff due to overall revenue reductions, but have increased acuity and complexity which requires more staffing. This puts even more of a burden on those of us still here.”

Support for institutional responses to slow the pandemic was strongest for state governments, which gained approval from 54% of front-line physicians, up from 33% in March. Actions taken by the federal government were supported by 21% of respondents, compared with 38% for the World Health Organization and 46% for governments outside the United States, InCrowd reported.

Suggestions for further actions by state and local authorities included this comment from an emergency/critical care physician in Florida: “Continued, broad and properly enforced stay at home and social distancing measures MUST remain in place to keep citizens and healthcare workers safe, and the latter alive and in adequate supply.”

rfranki@mdedge.com

A hematologist in Italy shared his personal experience addressing the intersection of COVID-19 and the care of acute myeloid leukemia (AML) patients during a webinar hosted by the European Hematology Association (EHA).

National Institutes of Health/Wikimedia Commons/Public Domain

Felicetto Ferrara, MD, of Cardarelli Hospital in Naples, Italy, discussed the main difficulties in administering optimal treatment for AML patients who become infected with SARS-CoV-2.

The major problems include the need to isolate patients while simultaneously allowing for collaboration with pulmonologists and intensivists, the delays in AML treatment caused by COVID-19, and the risk of drug-drug interactions while treating AML patients with COVID-19.

The need to isolate AML patients with COVID-19 is paramount, according to Dr. Ferrara. Isolation can be accomplished, ideally, by the creation of a dedicated COVID-19 unit or, alternatively, with the use of single-patient negative pressure rooms. Dr. Ferrara stressed that all patients with AML should be tested for COVID-19 before admission.
 

Delaying or reducing AML treatment

Treatment delays are of particular concern, according to Dr. Ferrara, and some patients may require dose reductions, especially for AML treatments that might have a detrimental effect on the immune system.

Decisions must be made as to whether planned approaches to induction or consolidation therapy should be changed, and special concern has to be paid to elderly AML patients, who have the highest risks of bad COVID-19 outcomes.

Specific attention should be paid to patients with acute promyelocytic leukemia as well, according to Dr. Ferrara. These patients are of concern in the COVID-19 era because of their risk of differentiation syndrome, which can induce respiratory distress.

In all cases, autologous or allogeneic stem cell transplant should be deferred until confirmed COVID-19–negative test results are obtained.
 

Continuing AML treatment

Of particular concern is the fact that, without a standard therapy for COVID-19, many different drugs might be used in treatment efforts. This raises the potential for serious drug-drug interactions with the patient’s AML medications, so close attention should be paid to an individual patient’s medications.

In terms of continuing AML treatment for younger adults (less than 65 years) who are positive for COVID-19, symptomatic and asymptomatic patients should be treated differently, Dr. Ferarra said.

Symptomatic patients should be given hydroxyurea until symptom resolution, and unless urgent, any further AML treatments should be delayed. However, if treatment is needed immediately, it should be given in a COVID-19–dedicated unit.

The restrictions are much looser for young adult asymptomatic COVID-19 patients with AML. Standard induction therapy should be given, with intermediate-dose cytarabine used as consolidation therapy.

Therapy in elderly patients with AML and COVID-19 should be based on symptom status as well, said Dr. Ferrara.

Asymptomatic but otherwise fit elderly patients should have standard induction therapy if they are in the European Leukemia Network favorable genetic subgroup. Asymptomatic elderly patients with high-risk molecular disease can receive venetoclax with a hypomethylating agent.

Symptomatic elderly patients should continue with hydroxyurea until symptom resolution, and any other treatments should be delayed in nonemergency cases.

Relapsed AML patients with COVID-19 should have their treatments postponed until they obtain negative COVID-19 test results whenever possible, Dr. Ferarra said. However, if treatment is necessary, molecularly targeted therapies (gilteritinib, ivosidenib, and enasidenib) are preferable to high-dose chemotherapy.

In all cases, treatment decisions should be made in conjunction with pulmonologists and intensivists, Dr. Ferrera noted.

Webinar moderator Francesco Cerisoli, MD, head of research and mentoring at EHA, highlighted the fact that EHA has published specific recommendations for treating AML patients during the COVID-19 pandemic. The majority of these were discussed by and are aligned with the recommendations presented by Dr. Ferrara.

The EHA webinar contains a disclaimer that the content discussed was based on the personal experiences and opinions of the speakers and that no general, evidence-based guidance could be derived from the discussion. There were no disclosures given.

mlesney@mdedge.com

A hematologist in Italy shared his personal experience addressing the intersection of COVID-19 and the care of acute myeloid leukemia (AML) patients during a webinar hosted by the European Hematology Association (EHA).

National Institutes of Health/Wikimedia Commons/Public Domain

Felicetto Ferrara, MD, of Cardarelli Hospital in Naples, Italy, discussed the main difficulties in administering optimal treatment for AML patients who become infected with SARS-CoV-2.

The major problems include the need to isolate patients while simultaneously allowing for collaboration with pulmonologists and intensivists, the delays in AML treatment caused by COVID-19, and the risk of drug-drug interactions while treating AML patients with COVID-19.

The need to isolate AML patients with COVID-19 is paramount, according to Dr. Ferrara. Isolation can be accomplished, ideally, by the creation of a dedicated COVID-19 unit or, alternatively, with the use of single-patient negative pressure rooms. Dr. Ferrara stressed that all patients with AML should be tested for COVID-19 before admission.
 

Delaying or reducing AML treatment

Treatment delays are of particular concern, according to Dr. Ferrara, and some patients may require dose reductions, especially for AML treatments that might have a detrimental effect on the immune system.

Decisions must be made as to whether planned approaches to induction or consolidation therapy should be changed, and special concern has to be paid to elderly AML patients, who have the highest risks of bad COVID-19 outcomes.

Specific attention should be paid to patients with acute promyelocytic leukemia as well, according to Dr. Ferrara. These patients are of concern in the COVID-19 era because of their risk of differentiation syndrome, which can induce respiratory distress.

In all cases, autologous or allogeneic stem cell transplant should be deferred until confirmed COVID-19–negative test results are obtained.
 

Continuing AML treatment

Of particular concern is the fact that, without a standard therapy for COVID-19, many different drugs might be used in treatment efforts. This raises the potential for serious drug-drug interactions with the patient’s AML medications, so close attention should be paid to an individual patient’s medications.

In terms of continuing AML treatment for younger adults (less than 65 years) who are positive for COVID-19, symptomatic and asymptomatic patients should be treated differently, Dr. Ferarra said.

Symptomatic patients should be given hydroxyurea until symptom resolution, and unless urgent, any further AML treatments should be delayed. However, if treatment is needed immediately, it should be given in a COVID-19–dedicated unit.

The restrictions are much looser for young adult asymptomatic COVID-19 patients with AML. Standard induction therapy should be given, with intermediate-dose cytarabine used as consolidation therapy.

Therapy in elderly patients with AML and COVID-19 should be based on symptom status as well, said Dr. Ferrara.

Asymptomatic but otherwise fit elderly patients should have standard induction therapy if they are in the European Leukemia Network favorable genetic subgroup. Asymptomatic elderly patients with high-risk molecular disease can receive venetoclax with a hypomethylating agent.

Symptomatic elderly patients should continue with hydroxyurea until symptom resolution, and any other treatments should be delayed in nonemergency cases.

Relapsed AML patients with COVID-19 should have their treatments postponed until they obtain negative COVID-19 test results whenever possible, Dr. Ferarra said. However, if treatment is necessary, molecularly targeted therapies (gilteritinib, ivosidenib, and enasidenib) are preferable to high-dose chemotherapy.

In all cases, treatment decisions should be made in conjunction with pulmonologists and intensivists, Dr. Ferrera noted.

Webinar moderator Francesco Cerisoli, MD, head of research and mentoring at EHA, highlighted the fact that EHA has published specific recommendations for treating AML patients during the COVID-19 pandemic. The majority of these were discussed by and are aligned with the recommendations presented by Dr. Ferrara.

The EHA webinar contains a disclaimer that the content discussed was based on the personal experiences and opinions of the speakers and that no general, evidence-based guidance could be derived from the discussion. There were no disclosures given.

mlesney@mdedge.com

A hematologist in Italy shared his personal experience addressing the intersection of COVID-19 and the care of acute myeloid leukemia (AML) patients during a webinar hosted by the European Hematology Association (EHA).

National Institutes of Health/Wikimedia Commons/Public Domain

Felicetto Ferrara, MD, of Cardarelli Hospital in Naples, Italy, discussed the main difficulties in administering optimal treatment for AML patients who become infected with SARS-CoV-2.

The major problems include the need to isolate patients while simultaneously allowing for collaboration with pulmonologists and intensivists, the delays in AML treatment caused by COVID-19, and the risk of drug-drug interactions while treating AML patients with COVID-19.

The need to isolate AML patients with COVID-19 is paramount, according to Dr. Ferrara. Isolation can be accomplished, ideally, by the creation of a dedicated COVID-19 unit or, alternatively, with the use of single-patient negative pressure rooms. Dr. Ferrara stressed that all patients with AML should be tested for COVID-19 before admission.
 

Delaying or reducing AML treatment

Treatment delays are of particular concern, according to Dr. Ferrara, and some patients may require dose reductions, especially for AML treatments that might have a detrimental effect on the immune system.

Decisions must be made as to whether planned approaches to induction or consolidation therapy should be changed, and special concern has to be paid to elderly AML patients, who have the highest risks of bad COVID-19 outcomes.

Specific attention should be paid to patients with acute promyelocytic leukemia as well, according to Dr. Ferrara. These patients are of concern in the COVID-19 era because of their risk of differentiation syndrome, which can induce respiratory distress.

In all cases, autologous or allogeneic stem cell transplant should be deferred until confirmed COVID-19–negative test results are obtained.
 

Continuing AML treatment

Of particular concern is the fact that, without a standard therapy for COVID-19, many different drugs might be used in treatment efforts. This raises the potential for serious drug-drug interactions with the patient’s AML medications, so close attention should be paid to an individual patient’s medications.

In terms of continuing AML treatment for younger adults (less than 65 years) who are positive for COVID-19, symptomatic and asymptomatic patients should be treated differently, Dr. Ferarra said.

Symptomatic patients should be given hydroxyurea until symptom resolution, and unless urgent, any further AML treatments should be delayed. However, if treatment is needed immediately, it should be given in a COVID-19–dedicated unit.

The restrictions are much looser for young adult asymptomatic COVID-19 patients with AML. Standard induction therapy should be given, with intermediate-dose cytarabine used as consolidation therapy.

Therapy in elderly patients with AML and COVID-19 should be based on symptom status as well, said Dr. Ferrara.

Asymptomatic but otherwise fit elderly patients should have standard induction therapy if they are in the European Leukemia Network favorable genetic subgroup. Asymptomatic elderly patients with high-risk molecular disease can receive venetoclax with a hypomethylating agent.

Symptomatic elderly patients should continue with hydroxyurea until symptom resolution, and any other treatments should be delayed in nonemergency cases.

Relapsed AML patients with COVID-19 should have their treatments postponed until they obtain negative COVID-19 test results whenever possible, Dr. Ferarra said. However, if treatment is necessary, molecularly targeted therapies (gilteritinib, ivosidenib, and enasidenib) are preferable to high-dose chemotherapy.

In all cases, treatment decisions should be made in conjunction with pulmonologists and intensivists, Dr. Ferrera noted.

Webinar moderator Francesco Cerisoli, MD, head of research and mentoring at EHA, highlighted the fact that EHA has published specific recommendations for treating AML patients during the COVID-19 pandemic. The majority of these were discussed by and are aligned with the recommendations presented by Dr. Ferrara.

The EHA webinar contains a disclaimer that the content discussed was based on the personal experiences and opinions of the speakers and that no general, evidence-based guidance could be derived from the discussion. There were no disclosures given.

mlesney@mdedge.com

The U.S. Food and Drug Administration reinforced its March guidance on when it’s permissible to use hydroxychloroquine and chloroquine to treat COVID-19 patients and on the multiple risks these drugs pose in a Safety Communication on April 24.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The new communication reiterated the agency’s position from the Emergency Use Authorization (EUA) it granted on March 28 to allow hydroxychloroquine and chloroquine treatment of COVID-19 patients only when they are hospitalized and participation in a clinical trial is “not available,” or “not feasible.” The April 24 update to the EUA noted that “the FDA is aware of reports of serious heart rhythm problems in patients with COVID-19 treated with hydroxychloroquine or chloroquine, often in combination with azithromycin and other QT-prolonging medicines. We are also aware of increased use of these medicines through outpatient prescriptions.”

In addition to reiterating the prior limitations on permissible patients for these treatment the agency also said in the new communication that “close supervision is strongly recommended, “ specifying that “we recommend initial evaluation and monitoring when using hydroxychloroquine or chloroquine under the EUA or in clinical trials that investigate these medicines for the treatment or prevention of COVID-19. Monitoring may include baseline ECG, electrolytes, renal function, and hepatic tests.” The communication also highlighted several potential serious adverse effects from hydroxychloroquine or chloroquine that include QT prolongation with increased risk in patients with renal insufficiency or failure, increased insulin levels and insulin action causing increased risk of severe hypoglycemia, hemolysis in selected patients, and interaction with other medicines that cause QT prolongation.

“If a healthcare professional is considering use of hydroxychloroquine or chloroquine to treat or prevent COVID-19, FDA recommends checking www.clinicaltrials.gov for a suitable clinical trial and consider enrolling the patient,” the statement added.

The FDA’s Safety Communication came a day after the European Medicines Agency issued a similar reminder about the risk for serious adverse effects from treatment with hydroxychloroquine and chloroquine, the need for adverse effect monitoring, and the unproven status of purported benefits from these agents.

The statement came after ongoing promotion by the Trump administration of hydroxychloroquine, in particular, for COVID-19 despite a lack of evidence.

The FDA’s communication cited recent case reports sent to the FDA, as well as published findings, and reports to the National Poison Data System that have described serious, heart-related adverse events and death in COVID-19 patients who received hydroxychloroquine and chloroquine, alone or in combination with azithromycin or another QT-prolonging drug. One recent, notable but not peer-reviewed report on 368 patients treated at any of several U.S. VA medical centers showed no apparent benefit to hospitalized COVID-19 patients treated with hydroxychloroquine and a signal for increased mortality among certain patients on this drug (medRxiv. 2020 Apr 23; doi: 10.1101/2020.04.16.20065920). Several cardiology societies have also highlighted the cardiac considerations for using these drugs in patients with COVID-19, including a summary coauthored by the presidents of the American College of Cardiology, the American Heart Association, and the Heart Rhythm Society (Circulation. 2020 Apr 8. doi: 10.1161/CIRCULATIONAHA.120.047521), and in guidance from the European Society of Cardiology.

mzoler@mdedge.com

The U.S. Food and Drug Administration reinforced its March guidance on when it’s permissible to use hydroxychloroquine and chloroquine to treat COVID-19 patients and on the multiple risks these drugs pose in a Safety Communication on April 24.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The new communication reiterated the agency’s position from the Emergency Use Authorization (EUA) it granted on March 28 to allow hydroxychloroquine and chloroquine treatment of COVID-19 patients only when they are hospitalized and participation in a clinical trial is “not available,” or “not feasible.” The April 24 update to the EUA noted that “the FDA is aware of reports of serious heart rhythm problems in patients with COVID-19 treated with hydroxychloroquine or chloroquine, often in combination with azithromycin and other QT-prolonging medicines. We are also aware of increased use of these medicines through outpatient prescriptions.”

In addition to reiterating the prior limitations on permissible patients for these treatment the agency also said in the new communication that “close supervision is strongly recommended, “ specifying that “we recommend initial evaluation and monitoring when using hydroxychloroquine or chloroquine under the EUA or in clinical trials that investigate these medicines for the treatment or prevention of COVID-19. Monitoring may include baseline ECG, electrolytes, renal function, and hepatic tests.” The communication also highlighted several potential serious adverse effects from hydroxychloroquine or chloroquine that include QT prolongation with increased risk in patients with renal insufficiency or failure, increased insulin levels and insulin action causing increased risk of severe hypoglycemia, hemolysis in selected patients, and interaction with other medicines that cause QT prolongation.

“If a healthcare professional is considering use of hydroxychloroquine or chloroquine to treat or prevent COVID-19, FDA recommends checking www.clinicaltrials.gov for a suitable clinical trial and consider enrolling the patient,” the statement added.

The FDA’s Safety Communication came a day after the European Medicines Agency issued a similar reminder about the risk for serious adverse effects from treatment with hydroxychloroquine and chloroquine, the need for adverse effect monitoring, and the unproven status of purported benefits from these agents.

The statement came after ongoing promotion by the Trump administration of hydroxychloroquine, in particular, for COVID-19 despite a lack of evidence.

The FDA’s communication cited recent case reports sent to the FDA, as well as published findings, and reports to the National Poison Data System that have described serious, heart-related adverse events and death in COVID-19 patients who received hydroxychloroquine and chloroquine, alone or in combination with azithromycin or another QT-prolonging drug. One recent, notable but not peer-reviewed report on 368 patients treated at any of several U.S. VA medical centers showed no apparent benefit to hospitalized COVID-19 patients treated with hydroxychloroquine and a signal for increased mortality among certain patients on this drug (medRxiv. 2020 Apr 23; doi: 10.1101/2020.04.16.20065920). Several cardiology societies have also highlighted the cardiac considerations for using these drugs in patients with COVID-19, including a summary coauthored by the presidents of the American College of Cardiology, the American Heart Association, and the Heart Rhythm Society (Circulation. 2020 Apr 8. doi: 10.1161/CIRCULATIONAHA.120.047521), and in guidance from the European Society of Cardiology.

mzoler@mdedge.com

The U.S. Food and Drug Administration reinforced its March guidance on when it’s permissible to use hydroxychloroquine and chloroquine to treat COVID-19 patients and on the multiple risks these drugs pose in a Safety Communication on April 24.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The new communication reiterated the agency’s position from the Emergency Use Authorization (EUA) it granted on March 28 to allow hydroxychloroquine and chloroquine treatment of COVID-19 patients only when they are hospitalized and participation in a clinical trial is “not available,” or “not feasible.” The April 24 update to the EUA noted that “the FDA is aware of reports of serious heart rhythm problems in patients with COVID-19 treated with hydroxychloroquine or chloroquine, often in combination with azithromycin and other QT-prolonging medicines. We are also aware of increased use of these medicines through outpatient prescriptions.”

In addition to reiterating the prior limitations on permissible patients for these treatment the agency also said in the new communication that “close supervision is strongly recommended, “ specifying that “we recommend initial evaluation and monitoring when using hydroxychloroquine or chloroquine under the EUA or in clinical trials that investigate these medicines for the treatment or prevention of COVID-19. Monitoring may include baseline ECG, electrolytes, renal function, and hepatic tests.” The communication also highlighted several potential serious adverse effects from hydroxychloroquine or chloroquine that include QT prolongation with increased risk in patients with renal insufficiency or failure, increased insulin levels and insulin action causing increased risk of severe hypoglycemia, hemolysis in selected patients, and interaction with other medicines that cause QT prolongation.

“If a healthcare professional is considering use of hydroxychloroquine or chloroquine to treat or prevent COVID-19, FDA recommends checking www.clinicaltrials.gov for a suitable clinical trial and consider enrolling the patient,” the statement added.

The FDA’s Safety Communication came a day after the European Medicines Agency issued a similar reminder about the risk for serious adverse effects from treatment with hydroxychloroquine and chloroquine, the need for adverse effect monitoring, and the unproven status of purported benefits from these agents.

The statement came after ongoing promotion by the Trump administration of hydroxychloroquine, in particular, for COVID-19 despite a lack of evidence.

The FDA’s communication cited recent case reports sent to the FDA, as well as published findings, and reports to the National Poison Data System that have described serious, heart-related adverse events and death in COVID-19 patients who received hydroxychloroquine and chloroquine, alone or in combination with azithromycin or another QT-prolonging drug. One recent, notable but not peer-reviewed report on 368 patients treated at any of several U.S. VA medical centers showed no apparent benefit to hospitalized COVID-19 patients treated with hydroxychloroquine and a signal for increased mortality among certain patients on this drug (medRxiv. 2020 Apr 23; doi: 10.1101/2020.04.16.20065920). Several cardiology societies have also highlighted the cardiac considerations for using these drugs in patients with COVID-19, including a summary coauthored by the presidents of the American College of Cardiology, the American Heart Association, and the Heart Rhythm Society (Circulation. 2020 Apr 8. doi: 10.1161/CIRCULATIONAHA.120.047521), and in guidance from the European Society of Cardiology.

mzoler@mdedge.com

Initial data from one Chinese center on the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) in patients hospitalized with COVID-19 appear to give some further reassurance about continued use of these drugs.

The report from one hospital in Wuhan found that among patients with hypertension hospitalized with the COVID-19 virus, there was no difference in disease severity or death rate in patients taking ACE inhibitors or ARBs and those not taking such medications.

The data were published online April 23 in JAMA Cardiology.

The study adds to another recent report in a larger number of COVID-19 patients from nine Chinese hospitals that suggested a beneficial effect of ACE inhibitors or ARBs on mortality.

Additional studies

Two other similar studies have also been recently released. Another study from China, published online March 31 in Emerging Microbes & Infections, included a small sample of 42 hospitalized patients with COVID-19 on antihypertensive therapy. Those on ACE inhibitor/ARB therapy had a lower rate of severe disease and a trend toward a lower level of IL-6 in peripheral blood. In addition, patients on ACE inhibitor/ARB therapy had increased CD3+ and CD8+ T-cell counts in peripheral blood and decreased peak viral load compared with other antihypertensive drugs.

And a preliminary study from the UK, which has not yet been peer reviewed, found that treatment with ACE inhibitors was associated with a reduced risk of rapidly deteriorating severe COVID-19 disease.

The study, available online on MedRxiv, a preprint server for health sciences, reports on 205 acute inpatients with COVID-19 at King’s College Hospital and Princess Royal University Hospital, London.

Of these, 51.2% had hypertension, 30.2% had diabetes, and 14.6% had ischemic heart disease or heart failure. Of the 37 patients on ACE inhibitors, five (14%) died or required critical care support compared with 29% (48/168) of patients not taking an ACE inhibitor.
 

New Wuhan study

The authors of the new article published in JAMA Cardiology, led by Juyi Li, MD, reported on a case series of 1,178 patients hospitalized with COVID-19 at the Central Hospital of Wuhan, Hubei, China, between Jan. 15 and March 15, 2020.

Patients were a median age of 55 years, and 46% were men. They had an overall in-hospital mortality rate of 11%.

Of the 1,178 patients, 362 (30.7%) had a diagnosis of hypertension. These patients were older (median age, 66 years) and had a greater prevalence of chronic diseases. Patients with hypertension also had more severe manifestations of COVID-19 compared to those without hypertension, including higher rates of acute respiratory distress syndrome and in-hospital mortality (21.3% vs. 6.5%).

Of the 362 patients with hypertension, 31.8% were taking ACE inhibitors or ARBs.

Apart from a greater prevalence of coronary artery disease, patients taking ACE inhibitors or ARBs had similar comorbidities to those not taking these medications, and also similar laboratory profile results including blood counts, inflammatory markers, renal and liver function tests, and cardiac biomarkers, although those taking ACE inhibitors/ARBs had higher levels of alkaline phosphatase.

The most commonly used antihypertensive drugs were calcium blockers. The percentage of patients with hypertension taking any drug or drug combination did not differ between those with severe and nonsevere infections and between those who survived and those who died.

Specifically regarding ACE inhibitors/ARBs, there was no difference between those with severe versus nonsevere illness in the use of ACE inhibitors (9.2% vs. 10.1%; P = .80), ARBs (24.9% vs. 21.2%; P = .40), or the composite of ACE inhibitors or ARBs (32.9% vs. 30.7%; P = .65).

Similarly, there were no differences in nonsurvivors and survivors in the use of ACE inhibitors (9.1% vs. 9.8%; P = .85); ARBs (19.5% vs. 23.9%; P = .42), or the composite of ACE inhibitors or ARBs (27.3% vs. 33.0%; P = .34).

The frequency of severe illness and death also did not differ between those treated with and without ACE inhibitors/ARBs in patients with hypertension and other various chronic conditions including coronary heart disease, cerebrovascular disease, diabetes, neurological disease, and chronic renal disease.

The authors noted that these data confirm previous reports showing that patients with hypertension have more severe illness and higher mortality rates associated with COVID-19 than those without hypertension.

But they added: “Our data provide some reassurance that ACE inhibitors/ARBs are not associated with the progression or outcome of COVID-19 hospitalizations in patients with hypertension.”

They also noted that these results support the recommendations from almost all major cardiovascular societies that patients do not discontinue ACE inhibitors or ARBs because of worries about COVID-19.

However, the authors did point out some limitations of their study, which included a small number of patients with hypertension taking ACE inhibitors or ARBs and the fact that a nonsevere disease course was still severe enough to require hospitalization. In addition, it was not clear whether ACE inhibitor/ARB treatment at baseline was maintained throughout hospitalization for all patients.

This was also an observational comparison and may be biased by differences in patients taking versus not taking ACE inhibitors or ARBs at the time of hospitalization, although the measured baseline characteristics were similar in both groups.

But the authors also highlighted the finding that, in this cohort, patients with hypertension had three times the mortality rate of all other patients hospitalized with COVID-19.

“Hypertension combined with cardiovascular and cerebrovascular disease, diabetes, and chronic kidney disease would predispose patients to an increased risk of severity and mortality of COVID-19. Therefore, patients with these underlying conditions who develop COVID-19 require particularly intensive surveillance and care,” they wrote.
 

Experts cautiously optimistic

Some cardiovascular experts were cautiously optimistic about these latest results.

Michael A. Weber, MD, professor of medicine at the State University of New York, Brooklyn, and editor-in-chief of the Journal of Clinical Hypertension, said: “This new report from Wuhan, China, gives modest reassurance that the use of ACE inhibitors or ARBs in hypertensive patients with COVID-19 disease does not increase the risk of clinical deterioration or death.

“Ongoing, more definitive studies should help resolve competing hypotheses regarding the effects of these agents: whether the increased ACE2 enzyme levels they produce can worsen outcomes by increasing access of the COVID virus to lung tissue; or whether there is a benefit linked to a protective effect of increased ACE2 on alveolar cell function,” Dr. Weber noted.

“Though the number of patients included in this new report is small, it is startling that hypertensive patients were three times as likely as nonhypertensives to have a fatal outcome, presumably reflecting vulnerability due to the cardiovascular and metabolic comorbidities associated with hypertension,” he added.

“In any case, for now, clinicians should continue treating hypertensive patients with whichever drugs, including ACE inhibitors and ARBs, best provide protection from adverse outcomes,” Dr. Weber concluded.

John McMurray, MD, professor of medical cardiology, University of Glasgow, Scotland, commented: “This study from Wuhan provides some reassurance about one of the two questions about ACEI/ARBs: Do these drugs increase susceptibility to infection? And if [the patient is] infected, do they increase the severity of infection? This study addresses the latter question and appears to suggest no increased severity.”

However, Dr. McMurray pointed out that the study had many limitations. There were only small patient numbers and the data were unadjusted, “although it looks like the ACE inhibitor/ARB treated patients were higher risk to start with.” It was an observational study, and patients were not randomized and were predominantly treated with ARBs, and not ACE inhibitors, so “we don’t know if the concerns apply equally to these two classes of drug.

“Other data published and unpublished supporting this (even showing better outcomes in patients treated with an ACE inhibitor/ARB), and, to date, any concerns about these drugs remain unsubstantiated and the guidance from medical societies to continue treatment with these agents in patients prescribed them seems wise,” Dr. McMurray added.

Franz H. Messerli, MD, professor of medicine at the University of Bern, Switzerland, commented: “The study from Wuhan is not a great study. They didn’t even do a multivariable analysis. They could have done a bit more with the data, but it still gives some reassurance.”

Dr. Messerli said it was “interesting” that 30% of the patients hospitalized with COVID-19 in the sample had hypertension. “That corresponds to the general population, so does not suggest that having hypertension increases susceptibility to infection – but it does seem to increase the risk of a bad outcome.”

Dr. Messerli noted that there are two more similar studies due to be published soon, both said to suggest either a beneficial or neutral effect of ACE inhibitors/ARBs on COVID-19 outcomes in hospitalized patients.

“This does help with confidence in prescribing these agents and reinforces the recommendations for patients to stay on these drugs,” he said.

“However, none of these studies address the infectivity issue – whether their use upregulates the ACE2 receptor, which the virus uses to gain entry to cells, thereby increasing susceptibility to the infection,” Dr. Messerli cautioned. “But the similar or better outcomes on these drugs are encouraging,” he added.

The Wuhan study was supported by the Health and Family Planning Commission of Wuhan City, China. The authors have reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Initial data from one Chinese center on the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) in patients hospitalized with COVID-19 appear to give some further reassurance about continued use of these drugs.

The report from one hospital in Wuhan found that among patients with hypertension hospitalized with the COVID-19 virus, there was no difference in disease severity or death rate in patients taking ACE inhibitors or ARBs and those not taking such medications.

The data were published online April 23 in JAMA Cardiology.

The study adds to another recent report in a larger number of COVID-19 patients from nine Chinese hospitals that suggested a beneficial effect of ACE inhibitors or ARBs on mortality.

Additional studies

Two other similar studies have also been recently released. Another study from China, published online March 31 in Emerging Microbes & Infections, included a small sample of 42 hospitalized patients with COVID-19 on antihypertensive therapy. Those on ACE inhibitor/ARB therapy had a lower rate of severe disease and a trend toward a lower level of IL-6 in peripheral blood. In addition, patients on ACE inhibitor/ARB therapy had increased CD3+ and CD8+ T-cell counts in peripheral blood and decreased peak viral load compared with other antihypertensive drugs.

And a preliminary study from the UK, which has not yet been peer reviewed, found that treatment with ACE inhibitors was associated with a reduced risk of rapidly deteriorating severe COVID-19 disease.

The study, available online on MedRxiv, a preprint server for health sciences, reports on 205 acute inpatients with COVID-19 at King’s College Hospital and Princess Royal University Hospital, London.

Of these, 51.2% had hypertension, 30.2% had diabetes, and 14.6% had ischemic heart disease or heart failure. Of the 37 patients on ACE inhibitors, five (14%) died or required critical care support compared with 29% (48/168) of patients not taking an ACE inhibitor.
 

New Wuhan study

The authors of the new article published in JAMA Cardiology, led by Juyi Li, MD, reported on a case series of 1,178 patients hospitalized with COVID-19 at the Central Hospital of Wuhan, Hubei, China, between Jan. 15 and March 15, 2020.

Patients were a median age of 55 years, and 46% were men. They had an overall in-hospital mortality rate of 11%.

Of the 1,178 patients, 362 (30.7%) had a diagnosis of hypertension. These patients were older (median age, 66 years) and had a greater prevalence of chronic diseases. Patients with hypertension also had more severe manifestations of COVID-19 compared to those without hypertension, including higher rates of acute respiratory distress syndrome and in-hospital mortality (21.3% vs. 6.5%).

Of the 362 patients with hypertension, 31.8% were taking ACE inhibitors or ARBs.

Apart from a greater prevalence of coronary artery disease, patients taking ACE inhibitors or ARBs had similar comorbidities to those not taking these medications, and also similar laboratory profile results including blood counts, inflammatory markers, renal and liver function tests, and cardiac biomarkers, although those taking ACE inhibitors/ARBs had higher levels of alkaline phosphatase.

The most commonly used antihypertensive drugs were calcium blockers. The percentage of patients with hypertension taking any drug or drug combination did not differ between those with severe and nonsevere infections and between those who survived and those who died.

Specifically regarding ACE inhibitors/ARBs, there was no difference between those with severe versus nonsevere illness in the use of ACE inhibitors (9.2% vs. 10.1%; P = .80), ARBs (24.9% vs. 21.2%; P = .40), or the composite of ACE inhibitors or ARBs (32.9% vs. 30.7%; P = .65).

Similarly, there were no differences in nonsurvivors and survivors in the use of ACE inhibitors (9.1% vs. 9.8%; P = .85); ARBs (19.5% vs. 23.9%; P = .42), or the composite of ACE inhibitors or ARBs (27.3% vs. 33.0%; P = .34).

The frequency of severe illness and death also did not differ between those treated with and without ACE inhibitors/ARBs in patients with hypertension and other various chronic conditions including coronary heart disease, cerebrovascular disease, diabetes, neurological disease, and chronic renal disease.

The authors noted that these data confirm previous reports showing that patients with hypertension have more severe illness and higher mortality rates associated with COVID-19 than those without hypertension.

But they added: “Our data provide some reassurance that ACE inhibitors/ARBs are not associated with the progression or outcome of COVID-19 hospitalizations in patients with hypertension.”

They also noted that these results support the recommendations from almost all major cardiovascular societies that patients do not discontinue ACE inhibitors or ARBs because of worries about COVID-19.

However, the authors did point out some limitations of their study, which included a small number of patients with hypertension taking ACE inhibitors or ARBs and the fact that a nonsevere disease course was still severe enough to require hospitalization. In addition, it was not clear whether ACE inhibitor/ARB treatment at baseline was maintained throughout hospitalization for all patients.

This was also an observational comparison and may be biased by differences in patients taking versus not taking ACE inhibitors or ARBs at the time of hospitalization, although the measured baseline characteristics were similar in both groups.

But the authors also highlighted the finding that, in this cohort, patients with hypertension had three times the mortality rate of all other patients hospitalized with COVID-19.

“Hypertension combined with cardiovascular and cerebrovascular disease, diabetes, and chronic kidney disease would predispose patients to an increased risk of severity and mortality of COVID-19. Therefore, patients with these underlying conditions who develop COVID-19 require particularly intensive surveillance and care,” they wrote.
 

Experts cautiously optimistic

Some cardiovascular experts were cautiously optimistic about these latest results.

Michael A. Weber, MD, professor of medicine at the State University of New York, Brooklyn, and editor-in-chief of the Journal of Clinical Hypertension, said: “This new report from Wuhan, China, gives modest reassurance that the use of ACE inhibitors or ARBs in hypertensive patients with COVID-19 disease does not increase the risk of clinical deterioration or death.

“Ongoing, more definitive studies should help resolve competing hypotheses regarding the effects of these agents: whether the increased ACE2 enzyme levels they produce can worsen outcomes by increasing access of the COVID virus to lung tissue; or whether there is a benefit linked to a protective effect of increased ACE2 on alveolar cell function,” Dr. Weber noted.

“Though the number of patients included in this new report is small, it is startling that hypertensive patients were three times as likely as nonhypertensives to have a fatal outcome, presumably reflecting vulnerability due to the cardiovascular and metabolic comorbidities associated with hypertension,” he added.

“In any case, for now, clinicians should continue treating hypertensive patients with whichever drugs, including ACE inhibitors and ARBs, best provide protection from adverse outcomes,” Dr. Weber concluded.

John McMurray, MD, professor of medical cardiology, University of Glasgow, Scotland, commented: “This study from Wuhan provides some reassurance about one of the two questions about ACEI/ARBs: Do these drugs increase susceptibility to infection? And if [the patient is] infected, do they increase the severity of infection? This study addresses the latter question and appears to suggest no increased severity.”

However, Dr. McMurray pointed out that the study had many limitations. There were only small patient numbers and the data were unadjusted, “although it looks like the ACE inhibitor/ARB treated patients were higher risk to start with.” It was an observational study, and patients were not randomized and were predominantly treated with ARBs, and not ACE inhibitors, so “we don’t know if the concerns apply equally to these two classes of drug.

“Other data published and unpublished supporting this (even showing better outcomes in patients treated with an ACE inhibitor/ARB), and, to date, any concerns about these drugs remain unsubstantiated and the guidance from medical societies to continue treatment with these agents in patients prescribed them seems wise,” Dr. McMurray added.

Franz H. Messerli, MD, professor of medicine at the University of Bern, Switzerland, commented: “The study from Wuhan is not a great study. They didn’t even do a multivariable analysis. They could have done a bit more with the data, but it still gives some reassurance.”

Dr. Messerli said it was “interesting” that 30% of the patients hospitalized with COVID-19 in the sample had hypertension. “That corresponds to the general population, so does not suggest that having hypertension increases susceptibility to infection – but it does seem to increase the risk of a bad outcome.”

Dr. Messerli noted that there are two more similar studies due to be published soon, both said to suggest either a beneficial or neutral effect of ACE inhibitors/ARBs on COVID-19 outcomes in hospitalized patients.

“This does help with confidence in prescribing these agents and reinforces the recommendations for patients to stay on these drugs,” he said.

“However, none of these studies address the infectivity issue – whether their use upregulates the ACE2 receptor, which the virus uses to gain entry to cells, thereby increasing susceptibility to the infection,” Dr. Messerli cautioned. “But the similar or better outcomes on these drugs are encouraging,” he added.

The Wuhan study was supported by the Health and Family Planning Commission of Wuhan City, China. The authors have reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Initial data from one Chinese center on the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) in patients hospitalized with COVID-19 appear to give some further reassurance about continued use of these drugs.

The report from one hospital in Wuhan found that among patients with hypertension hospitalized with the COVID-19 virus, there was no difference in disease severity or death rate in patients taking ACE inhibitors or ARBs and those not taking such medications.

The data were published online April 23 in JAMA Cardiology.

The study adds to another recent report in a larger number of COVID-19 patients from nine Chinese hospitals that suggested a beneficial effect of ACE inhibitors or ARBs on mortality.

Additional studies

Two other similar studies have also been recently released. Another study from China, published online March 31 in Emerging Microbes & Infections, included a small sample of 42 hospitalized patients with COVID-19 on antihypertensive therapy. Those on ACE inhibitor/ARB therapy had a lower rate of severe disease and a trend toward a lower level of IL-6 in peripheral blood. In addition, patients on ACE inhibitor/ARB therapy had increased CD3+ and CD8+ T-cell counts in peripheral blood and decreased peak viral load compared with other antihypertensive drugs.

And a preliminary study from the UK, which has not yet been peer reviewed, found that treatment with ACE inhibitors was associated with a reduced risk of rapidly deteriorating severe COVID-19 disease.

The study, available online on MedRxiv, a preprint server for health sciences, reports on 205 acute inpatients with COVID-19 at King’s College Hospital and Princess Royal University Hospital, London.

Of these, 51.2% had hypertension, 30.2% had diabetes, and 14.6% had ischemic heart disease or heart failure. Of the 37 patients on ACE inhibitors, five (14%) died or required critical care support compared with 29% (48/168) of patients not taking an ACE inhibitor.
 

New Wuhan study

The authors of the new article published in JAMA Cardiology, led by Juyi Li, MD, reported on a case series of 1,178 patients hospitalized with COVID-19 at the Central Hospital of Wuhan, Hubei, China, between Jan. 15 and March 15, 2020.

Patients were a median age of 55 years, and 46% were men. They had an overall in-hospital mortality rate of 11%.

Of the 1,178 patients, 362 (30.7%) had a diagnosis of hypertension. These patients were older (median age, 66 years) and had a greater prevalence of chronic diseases. Patients with hypertension also had more severe manifestations of COVID-19 compared to those without hypertension, including higher rates of acute respiratory distress syndrome and in-hospital mortality (21.3% vs. 6.5%).

Of the 362 patients with hypertension, 31.8% were taking ACE inhibitors or ARBs.

Apart from a greater prevalence of coronary artery disease, patients taking ACE inhibitors or ARBs had similar comorbidities to those not taking these medications, and also similar laboratory profile results including blood counts, inflammatory markers, renal and liver function tests, and cardiac biomarkers, although those taking ACE inhibitors/ARBs had higher levels of alkaline phosphatase.

The most commonly used antihypertensive drugs were calcium blockers. The percentage of patients with hypertension taking any drug or drug combination did not differ between those with severe and nonsevere infections and between those who survived and those who died.

Specifically regarding ACE inhibitors/ARBs, there was no difference between those with severe versus nonsevere illness in the use of ACE inhibitors (9.2% vs. 10.1%; P = .80), ARBs (24.9% vs. 21.2%; P = .40), or the composite of ACE inhibitors or ARBs (32.9% vs. 30.7%; P = .65).

Similarly, there were no differences in nonsurvivors and survivors in the use of ACE inhibitors (9.1% vs. 9.8%; P = .85); ARBs (19.5% vs. 23.9%; P = .42), or the composite of ACE inhibitors or ARBs (27.3% vs. 33.0%; P = .34).

The frequency of severe illness and death also did not differ between those treated with and without ACE inhibitors/ARBs in patients with hypertension and other various chronic conditions including coronary heart disease, cerebrovascular disease, diabetes, neurological disease, and chronic renal disease.

The authors noted that these data confirm previous reports showing that patients with hypertension have more severe illness and higher mortality rates associated with COVID-19 than those without hypertension.

But they added: “Our data provide some reassurance that ACE inhibitors/ARBs are not associated with the progression or outcome of COVID-19 hospitalizations in patients with hypertension.”

They also noted that these results support the recommendations from almost all major cardiovascular societies that patients do not discontinue ACE inhibitors or ARBs because of worries about COVID-19.

However, the authors did point out some limitations of their study, which included a small number of patients with hypertension taking ACE inhibitors or ARBs and the fact that a nonsevere disease course was still severe enough to require hospitalization. In addition, it was not clear whether ACE inhibitor/ARB treatment at baseline was maintained throughout hospitalization for all patients.

This was also an observational comparison and may be biased by differences in patients taking versus not taking ACE inhibitors or ARBs at the time of hospitalization, although the measured baseline characteristics were similar in both groups.

But the authors also highlighted the finding that, in this cohort, patients with hypertension had three times the mortality rate of all other patients hospitalized with COVID-19.

“Hypertension combined with cardiovascular and cerebrovascular disease, diabetes, and chronic kidney disease would predispose patients to an increased risk of severity and mortality of COVID-19. Therefore, patients with these underlying conditions who develop COVID-19 require particularly intensive surveillance and care,” they wrote.
 

Experts cautiously optimistic

Some cardiovascular experts were cautiously optimistic about these latest results.

Michael A. Weber, MD, professor of medicine at the State University of New York, Brooklyn, and editor-in-chief of the Journal of Clinical Hypertension, said: “This new report from Wuhan, China, gives modest reassurance that the use of ACE inhibitors or ARBs in hypertensive patients with COVID-19 disease does not increase the risk of clinical deterioration or death.

“Ongoing, more definitive studies should help resolve competing hypotheses regarding the effects of these agents: whether the increased ACE2 enzyme levels they produce can worsen outcomes by increasing access of the COVID virus to lung tissue; or whether there is a benefit linked to a protective effect of increased ACE2 on alveolar cell function,” Dr. Weber noted.

“Though the number of patients included in this new report is small, it is startling that hypertensive patients were three times as likely as nonhypertensives to have a fatal outcome, presumably reflecting vulnerability due to the cardiovascular and metabolic comorbidities associated with hypertension,” he added.

“In any case, for now, clinicians should continue treating hypertensive patients with whichever drugs, including ACE inhibitors and ARBs, best provide protection from adverse outcomes,” Dr. Weber concluded.

John McMurray, MD, professor of medical cardiology, University of Glasgow, Scotland, commented: “This study from Wuhan provides some reassurance about one of the two questions about ACEI/ARBs: Do these drugs increase susceptibility to infection? And if [the patient is] infected, do they increase the severity of infection? This study addresses the latter question and appears to suggest no increased severity.”

However, Dr. McMurray pointed out that the study had many limitations. There were only small patient numbers and the data were unadjusted, “although it looks like the ACE inhibitor/ARB treated patients were higher risk to start with.” It was an observational study, and patients were not randomized and were predominantly treated with ARBs, and not ACE inhibitors, so “we don’t know if the concerns apply equally to these two classes of drug.

“Other data published and unpublished supporting this (even showing better outcomes in patients treated with an ACE inhibitor/ARB), and, to date, any concerns about these drugs remain unsubstantiated and the guidance from medical societies to continue treatment with these agents in patients prescribed them seems wise,” Dr. McMurray added.

Franz H. Messerli, MD, professor of medicine at the University of Bern, Switzerland, commented: “The study from Wuhan is not a great study. They didn’t even do a multivariable analysis. They could have done a bit more with the data, but it still gives some reassurance.”

Dr. Messerli said it was “interesting” that 30% of the patients hospitalized with COVID-19 in the sample had hypertension. “That corresponds to the general population, so does not suggest that having hypertension increases susceptibility to infection – but it does seem to increase the risk of a bad outcome.”

Dr. Messerli noted that there are two more similar studies due to be published soon, both said to suggest either a beneficial or neutral effect of ACE inhibitors/ARBs on COVID-19 outcomes in hospitalized patients.

“This does help with confidence in prescribing these agents and reinforces the recommendations for patients to stay on these drugs,” he said.

“However, none of these studies address the infectivity issue – whether their use upregulates the ACE2 receptor, which the virus uses to gain entry to cells, thereby increasing susceptibility to the infection,” Dr. Messerli cautioned. “But the similar or better outcomes on these drugs are encouraging,” he added.

The Wuhan study was supported by the Health and Family Planning Commission of Wuhan City, China. The authors have reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Hydroxychloroquine (HCQ) with or without azithromycin (AZ) is not associated with a lower risk of requiring mechanical ventilation, according to a retrospective study of Veterans Affairs patients hospitalized with COVID-19.

The study, which was posted on a preprint server April 21 and has not been peer reviewed, also showed an increased risk of death associated with COVID-19 patients treated with HCQ alone.

“These findings highlight the importance of awaiting the results of ongoing prospective, randomized controlled studies before widespread adoption of these drugs,” write Joseph Magagnoli with Dorn Research Institute at the Columbia (S.C.) VA Health Care System and the department of clinical pharmacy & outcomes sciences, University of South Carolina, and colleagues.

A spokesperson with the University of Virginia, Charlottesville, where several of coauthors practice, said that the authors declined to comment for this article before peer review is completed.

The new data are not the first to suggest no benefit with HCQ among patients with COVID-19. A randomized trial showed no benefit and more side effects among 75 patients in China treated with HCQ, compared with 75 who received standard of care alone, according to a preprint posted online April 14.

No benefit in ventilation, death rates

The current analysis included data from all 368 male patients hospitalized with confirmed COVID-19 and treated at Veterans Health Administration medical centers in the United States through April 11.

Patients were categorized into three groups: those treated with HCQ in addition to standard of care (n = 97); those treated with HCQ and the antibiotic azithromycin plus standard of care (n = 113); and those who received standard supportive care only (n = 158).

Wait for convincing data

Dr. Wessner, whose research focuses on viral pathogenesis, says that, although the current data don’t definitively answer the question of whether HCQ is effective in treating COVID-19, taking a “let’s try it and see” approach is not reasonable.

“Until we have good, prospective randomized trials, it’s hard to know what to make of this. But this is more evidence that there’s not a good reason to use [HCQ],” Dr. Wessner said. He points out that the small randomized trial from China shows that HCQ comes with potential harms.

Anecdotal evidence is often cited by those who promote HCQ as a potential treatment, but “those are one-off examples,” Wessner continued. “That doesn’t really tell us anything.”

Some HCQ proponents have said that trials finding no benefit are flawed in that the drug is given too late. However, Dr. Wessner says, there’s no way to prove or disprove that claim without randomized controlled trials.

Conflicting messages

Despite lack of clear evidence of benefit for patients with COVID-19, HCQ is recommended off-label by the Chinese National guideline, and the U.S. Food and Drug Administration has issued an emergency-use authorization for the treatment of adult patients with COVID-19.

Conversely, the Infectious Diseases Society of America and a guideline panel convened by the National Institutes of Health each concluded recently that because of insufficient data, they could not recommend any specific treatments for patients with COVID-19.

The VA data for the current study came from the Veterans Affairs Informatics and Computing Infrastructure, which includes inpatient, outpatient and laboratory data and pharmacy claims.

The authors acknowledge some limitations, “including those inherent to all retrospective analyses such as nonrandomization of treatments.”

However, they note that they did adjust for potential confounders, including comorbidities, medications, and clinical and laboratory factors.

A coauthor, Jayakrishna Ambati, MD, is a cofounder of iVeena Holdings, iVeena Delivery Systems and Inflammasome Therapeutics, and has received consultancy fees from Allergan, Biogen, Boehringer Ingelheim, Immunovant, Janssen, Olix Pharmaceuticals, Retinal Solutions, and Saksin LifeSciences, all unrelated to this work. Dr. Ambati is named as an inventor on a patent application filed by the University of Virginia relating to COVID-19 but unrelated to this work. Another coauthor has received research grants from Boehringer Ingelheim, Gilead Sciences, Portola Pharmaceuticals, and United Therapeutics, all unrelated to this work. The other authors and Dr. Wessner have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Hydroxychloroquine (HCQ) with or without azithromycin (AZ) is not associated with a lower risk of requiring mechanical ventilation, according to a retrospective study of Veterans Affairs patients hospitalized with COVID-19.

The study, which was posted on a preprint server April 21 and has not been peer reviewed, also showed an increased risk of death associated with COVID-19 patients treated with HCQ alone.

“These findings highlight the importance of awaiting the results of ongoing prospective, randomized controlled studies before widespread adoption of these drugs,” write Joseph Magagnoli with Dorn Research Institute at the Columbia (S.C.) VA Health Care System and the department of clinical pharmacy & outcomes sciences, University of South Carolina, and colleagues.

A spokesperson with the University of Virginia, Charlottesville, where several of coauthors practice, said that the authors declined to comment for this article before peer review is completed.

The new data are not the first to suggest no benefit with HCQ among patients with COVID-19. A randomized trial showed no benefit and more side effects among 75 patients in China treated with HCQ, compared with 75 who received standard of care alone, according to a preprint posted online April 14.

No benefit in ventilation, death rates

The current analysis included data from all 368 male patients hospitalized with confirmed COVID-19 and treated at Veterans Health Administration medical centers in the United States through April 11.

Patients were categorized into three groups: those treated with HCQ in addition to standard of care (n = 97); those treated with HCQ and the antibiotic azithromycin plus standard of care (n = 113); and those who received standard supportive care only (n = 158).

Wait for convincing data

Dr. Wessner, whose research focuses on viral pathogenesis, says that, although the current data don’t definitively answer the question of whether HCQ is effective in treating COVID-19, taking a “let’s try it and see” approach is not reasonable.

“Until we have good, prospective randomized trials, it’s hard to know what to make of this. But this is more evidence that there’s not a good reason to use [HCQ],” Dr. Wessner said. He points out that the small randomized trial from China shows that HCQ comes with potential harms.

Anecdotal evidence is often cited by those who promote HCQ as a potential treatment, but “those are one-off examples,” Wessner continued. “That doesn’t really tell us anything.”

Some HCQ proponents have said that trials finding no benefit are flawed in that the drug is given too late. However, Dr. Wessner says, there’s no way to prove or disprove that claim without randomized controlled trials.

Conflicting messages

Despite lack of clear evidence of benefit for patients with COVID-19, HCQ is recommended off-label by the Chinese National guideline, and the U.S. Food and Drug Administration has issued an emergency-use authorization for the treatment of adult patients with COVID-19.

Conversely, the Infectious Diseases Society of America and a guideline panel convened by the National Institutes of Health each concluded recently that because of insufficient data, they could not recommend any specific treatments for patients with COVID-19.

The VA data for the current study came from the Veterans Affairs Informatics and Computing Infrastructure, which includes inpatient, outpatient and laboratory data and pharmacy claims.

The authors acknowledge some limitations, “including those inherent to all retrospective analyses such as nonrandomization of treatments.”

However, they note that they did adjust for potential confounders, including comorbidities, medications, and clinical and laboratory factors.

A coauthor, Jayakrishna Ambati, MD, is a cofounder of iVeena Holdings, iVeena Delivery Systems and Inflammasome Therapeutics, and has received consultancy fees from Allergan, Biogen, Boehringer Ingelheim, Immunovant, Janssen, Olix Pharmaceuticals, Retinal Solutions, and Saksin LifeSciences, all unrelated to this work. Dr. Ambati is named as an inventor on a patent application filed by the University of Virginia relating to COVID-19 but unrelated to this work. Another coauthor has received research grants from Boehringer Ingelheim, Gilead Sciences, Portola Pharmaceuticals, and United Therapeutics, all unrelated to this work. The other authors and Dr. Wessner have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Hydroxychloroquine (HCQ) with or without azithromycin (AZ) is not associated with a lower risk of requiring mechanical ventilation, according to a retrospective study of Veterans Affairs patients hospitalized with COVID-19.

The study, which was posted on a preprint server April 21 and has not been peer reviewed, also showed an increased risk of death associated with COVID-19 patients treated with HCQ alone.

“These findings highlight the importance of awaiting the results of ongoing prospective, randomized controlled studies before widespread adoption of these drugs,” write Joseph Magagnoli with Dorn Research Institute at the Columbia (S.C.) VA Health Care System and the department of clinical pharmacy & outcomes sciences, University of South Carolina, and colleagues.

A spokesperson with the University of Virginia, Charlottesville, where several of coauthors practice, said that the authors declined to comment for this article before peer review is completed.

The new data are not the first to suggest no benefit with HCQ among patients with COVID-19. A randomized trial showed no benefit and more side effects among 75 patients in China treated with HCQ, compared with 75 who received standard of care alone, according to a preprint posted online April 14.

No benefit in ventilation, death rates

The current analysis included data from all 368 male patients hospitalized with confirmed COVID-19 and treated at Veterans Health Administration medical centers in the United States through April 11.

Patients were categorized into three groups: those treated with HCQ in addition to standard of care (n = 97); those treated with HCQ and the antibiotic azithromycin plus standard of care (n = 113); and those who received standard supportive care only (n = 158).

Wait for convincing data

Dr. Wessner, whose research focuses on viral pathogenesis, says that, although the current data don’t definitively answer the question of whether HCQ is effective in treating COVID-19, taking a “let’s try it and see” approach is not reasonable.

“Until we have good, prospective randomized trials, it’s hard to know what to make of this. But this is more evidence that there’s not a good reason to use [HCQ],” Dr. Wessner said. He points out that the small randomized trial from China shows that HCQ comes with potential harms.

Anecdotal evidence is often cited by those who promote HCQ as a potential treatment, but “those are one-off examples,” Wessner continued. “That doesn’t really tell us anything.”

Some HCQ proponents have said that trials finding no benefit are flawed in that the drug is given too late. However, Dr. Wessner says, there’s no way to prove or disprove that claim without randomized controlled trials.

Conflicting messages

Despite lack of clear evidence of benefit for patients with COVID-19, HCQ is recommended off-label by the Chinese National guideline, and the U.S. Food and Drug Administration has issued an emergency-use authorization for the treatment of adult patients with COVID-19.

Conversely, the Infectious Diseases Society of America and a guideline panel convened by the National Institutes of Health each concluded recently that because of insufficient data, they could not recommend any specific treatments for patients with COVID-19.

The VA data for the current study came from the Veterans Affairs Informatics and Computing Infrastructure, which includes inpatient, outpatient and laboratory data and pharmacy claims.

The authors acknowledge some limitations, “including those inherent to all retrospective analyses such as nonrandomization of treatments.”

However, they note that they did adjust for potential confounders, including comorbidities, medications, and clinical and laboratory factors.

A coauthor, Jayakrishna Ambati, MD, is a cofounder of iVeena Holdings, iVeena Delivery Systems and Inflammasome Therapeutics, and has received consultancy fees from Allergan, Biogen, Boehringer Ingelheim, Immunovant, Janssen, Olix Pharmaceuticals, Retinal Solutions, and Saksin LifeSciences, all unrelated to this work. Dr. Ambati is named as an inventor on a patent application filed by the University of Virginia relating to COVID-19 but unrelated to this work. Another coauthor has received research grants from Boehringer Ingelheim, Gilead Sciences, Portola Pharmaceuticals, and United Therapeutics, all unrelated to this work. The other authors and Dr. Wessner have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Ruxolitinib produced significantly better efficacy outcomes in patients with glucocorticoid-refractory acute graft-versus-host disease (GVHD), compared with investigator’s choice of control therapy, in the phase 3 REACH2 trial.

However, there was a higher incidence of thrombocytopenia with ruxolitinib than with control treatment, according to a report by Robert Zeiser, MD, of University of Freiburg (Germany) and colleagues on behalf of the REACH2 research group. The report was published in the New England Journal of Medicine.

The REACH2 trial (NCT02913261) is a randomized, open-label, phase 3 trial comparing the efficacy and safety of oral ruxolitinib (10 mg twice daily) with investigator’s choice of therapy for control treatment using a list of nine commonly used options.

Patients were 12 years of age or older with glucocorticoid-refractory acute GVHD after allogeneic stem cell transplant. A total of 154 patients were assigned to the ruxolitinib group, and 155 patients were in the control group.

Most patients – 152 in the ruxolitinib group and 150 in the control group – received at least one dose of trial treatment.

Treatment discontinuation occurred in 72% (111/154) of patients in the ruxolitinib group and in 85% (132/155) of those in the control group. The most common reason for discontinuation was lack of efficacy (in 21% and 44%, respectively).
 

Outcomes

The overall response at day 28 (the primary endpoint) was significantly higher in the ruxolitinib group than in the control group (62% vs. 39%; odds ratio, 2.64; P < .001). The durable overall response at day 56 was also significantly higher in the ruxolitinib group than in the control group (40% vs. 22%; OR, 2.38; P < .001).

The estimated cumulative incidence of loss of response at 6 months was 10% in the ruxolitinib group compared with 39% in the control group.

The median failure-free survival was considerably longer with ruxolitinib than with control treatment (5.0 months vs. 1.0 month; hazard ratio for relapse or progression of hematologic disease, non–relapse-related death, or the use of new systemic therapy for acute GVHD, 0.46).

The median overall survival was 11.1 months in the ruxolitinib group and 6.5 months in the control group (HR, 0.83).

Overall, 72 patients (47%) in the ruxolitinib group and 77 (51%) in the control group died by the data cutoff date. Most deaths were attributed to acute GVHD (22% in the ruxolitinib group and 25% in the control group).

The most common adverse events at day 28 (in the ruxolitinib and control arms, respectively) were thrombocytopenia (33% and 18%), anemia (30% and 28%), and cytomegalovirus infection (26% and 21%).
 

Praise for ‘successful’ randomized trial in GVHD

“The authors are to be congratulated for completing this successful randomized trial, which showed convincingly that ruxolitinib was more effective than the investigator’s choice of therapy ... in patients in whom glucocorticoid therapy had failed,” wrote Nelson Chao, MD, of Duke University in Durham, N.C., in his invited editorial.

He went on to speculate on the possible mechanism for ruxolitinib in these patients, discussing the possible role of the STAT3 and STAT1 signaling pathways.

Dr. Chao also found it “interesting that the incidence of infectious complications or relapse was apparently not greater with ruxolitinib than with control therapy,” but he noted that the total follow-up time was short.

“As with all good research, these observations raise important questions and set the stage for further work in this area,” he concluded.

The REACH2 trial was funded by Novartis. The study authors disclosed relationships with a variety of pharmaceutical companies, including Novartis. Dr. Chao reported having no relevant disclosures.

mlesney@mdedge.com

SOURCE: Zeiser R et al. N Engl J Med. 2020. doi: 10.1056/NEJMoa1917635.

Ruxolitinib produced significantly better efficacy outcomes in patients with glucocorticoid-refractory acute graft-versus-host disease (GVHD), compared with investigator’s choice of control therapy, in the phase 3 REACH2 trial.

However, there was a higher incidence of thrombocytopenia with ruxolitinib than with control treatment, according to a report by Robert Zeiser, MD, of University of Freiburg (Germany) and colleagues on behalf of the REACH2 research group. The report was published in the New England Journal of Medicine.

The REACH2 trial (NCT02913261) is a randomized, open-label, phase 3 trial comparing the efficacy and safety of oral ruxolitinib (10 mg twice daily) with investigator’s choice of therapy for control treatment using a list of nine commonly used options.

Patients were 12 years of age or older with glucocorticoid-refractory acute GVHD after allogeneic stem cell transplant. A total of 154 patients were assigned to the ruxolitinib group, and 155 patients were in the control group.

Most patients – 152 in the ruxolitinib group and 150 in the control group – received at least one dose of trial treatment.

Treatment discontinuation occurred in 72% (111/154) of patients in the ruxolitinib group and in 85% (132/155) of those in the control group. The most common reason for discontinuation was lack of efficacy (in 21% and 44%, respectively).
 

Outcomes

The overall response at day 28 (the primary endpoint) was significantly higher in the ruxolitinib group than in the control group (62% vs. 39%; odds ratio, 2.64; P < .001). The durable overall response at day 56 was also significantly higher in the ruxolitinib group than in the control group (40% vs. 22%; OR, 2.38; P < .001).

The estimated cumulative incidence of loss of response at 6 months was 10% in the ruxolitinib group compared with 39% in the control group.

The median failure-free survival was considerably longer with ruxolitinib than with control treatment (5.0 months vs. 1.0 month; hazard ratio for relapse or progression of hematologic disease, non–relapse-related death, or the use of new systemic therapy for acute GVHD, 0.46).

The median overall survival was 11.1 months in the ruxolitinib group and 6.5 months in the control group (HR, 0.83).

Overall, 72 patients (47%) in the ruxolitinib group and 77 (51%) in the control group died by the data cutoff date. Most deaths were attributed to acute GVHD (22% in the ruxolitinib group and 25% in the control group).

The most common adverse events at day 28 (in the ruxolitinib and control arms, respectively) were thrombocytopenia (33% and 18%), anemia (30% and 28%), and cytomegalovirus infection (26% and 21%).
 

Praise for ‘successful’ randomized trial in GVHD

“The authors are to be congratulated for completing this successful randomized trial, which showed convincingly that ruxolitinib was more effective than the investigator’s choice of therapy ... in patients in whom glucocorticoid therapy had failed,” wrote Nelson Chao, MD, of Duke University in Durham, N.C., in his invited editorial.

He went on to speculate on the possible mechanism for ruxolitinib in these patients, discussing the possible role of the STAT3 and STAT1 signaling pathways.

Dr. Chao also found it “interesting that the incidence of infectious complications or relapse was apparently not greater with ruxolitinib than with control therapy,” but he noted that the total follow-up time was short.

“As with all good research, these observations raise important questions and set the stage for further work in this area,” he concluded.

The REACH2 trial was funded by Novartis. The study authors disclosed relationships with a variety of pharmaceutical companies, including Novartis. Dr. Chao reported having no relevant disclosures.

mlesney@mdedge.com

SOURCE: Zeiser R et al. N Engl J Med. 2020. doi: 10.1056/NEJMoa1917635.

Ruxolitinib produced significantly better efficacy outcomes in patients with glucocorticoid-refractory acute graft-versus-host disease (GVHD), compared with investigator’s choice of control therapy, in the phase 3 REACH2 trial.

However, there was a higher incidence of thrombocytopenia with ruxolitinib than with control treatment, according to a report by Robert Zeiser, MD, of University of Freiburg (Germany) and colleagues on behalf of the REACH2 research group. The report was published in the New England Journal of Medicine.

The REACH2 trial (NCT02913261) is a randomized, open-label, phase 3 trial comparing the efficacy and safety of oral ruxolitinib (10 mg twice daily) with investigator’s choice of therapy for control treatment using a list of nine commonly used options.

Patients were 12 years of age or older with glucocorticoid-refractory acute GVHD after allogeneic stem cell transplant. A total of 154 patients were assigned to the ruxolitinib group, and 155 patients were in the control group.

Most patients – 152 in the ruxolitinib group and 150 in the control group – received at least one dose of trial treatment.

Treatment discontinuation occurred in 72% (111/154) of patients in the ruxolitinib group and in 85% (132/155) of those in the control group. The most common reason for discontinuation was lack of efficacy (in 21% and 44%, respectively).
 

Outcomes

The overall response at day 28 (the primary endpoint) was significantly higher in the ruxolitinib group than in the control group (62% vs. 39%; odds ratio, 2.64; P < .001). The durable overall response at day 56 was also significantly higher in the ruxolitinib group than in the control group (40% vs. 22%; OR, 2.38; P < .001).

The estimated cumulative incidence of loss of response at 6 months was 10% in the ruxolitinib group compared with 39% in the control group.

The median failure-free survival was considerably longer with ruxolitinib than with control treatment (5.0 months vs. 1.0 month; hazard ratio for relapse or progression of hematologic disease, non–relapse-related death, or the use of new systemic therapy for acute GVHD, 0.46).

The median overall survival was 11.1 months in the ruxolitinib group and 6.5 months in the control group (HR, 0.83).

Overall, 72 patients (47%) in the ruxolitinib group and 77 (51%) in the control group died by the data cutoff date. Most deaths were attributed to acute GVHD (22% in the ruxolitinib group and 25% in the control group).

The most common adverse events at day 28 (in the ruxolitinib and control arms, respectively) were thrombocytopenia (33% and 18%), anemia (30% and 28%), and cytomegalovirus infection (26% and 21%).
 

Praise for ‘successful’ randomized trial in GVHD

“The authors are to be congratulated for completing this successful randomized trial, which showed convincingly that ruxolitinib was more effective than the investigator’s choice of therapy ... in patients in whom glucocorticoid therapy had failed,” wrote Nelson Chao, MD, of Duke University in Durham, N.C., in his invited editorial.

He went on to speculate on the possible mechanism for ruxolitinib in these patients, discussing the possible role of the STAT3 and STAT1 signaling pathways.

Dr. Chao also found it “interesting that the incidence of infectious complications or relapse was apparently not greater with ruxolitinib than with control therapy,” but he noted that the total follow-up time was short.

“As with all good research, these observations raise important questions and set the stage for further work in this area,” he concluded.

The REACH2 trial was funded by Novartis. The study authors disclosed relationships with a variety of pharmaceutical companies, including Novartis. Dr. Chao reported having no relevant disclosures.

mlesney@mdedge.com

SOURCE: Zeiser R et al. N Engl J Med. 2020. doi: 10.1056/NEJMoa1917635.