Myelodysplastic Syndrome

Key clinical point: Azacitidine was safe but had no significant impact on relapse-free survival after transplant in in patients with acute myeloid leukemia/myelodysplastic syndrome 

Major finding: Median relapse-free survival (RFS) was 2.07 years in the azacitidine group vs. 1.28 years in the control group (P = .19). 

Study details: The data come from a phase 3 open-label randomized trial of 187 patients aged 18 to 75 years with acute myeloid leukemia/myelodysplastic syndrome (AML/MDS); patients received 32 mg/m2 of azacitidine daily for 5 days every 28 days for 12 cycles.

Disclosures: The study was supported by Celgene Pharmaceuticals. Lead author Dr. Oran disclosed serving as a consultant for Celgene and receiving research funding from AROG Pharmaceuticals and Astex Pharmaceuticals.

Source: Oran B et al. Blood Adv. 2020 Nov 10. doi: 10.1182/bloodadvances.2020002544.

Key clinical point: Azacitidine was safe but had no significant impact on relapse-free survival after transplant in in patients with acute myeloid leukemia/myelodysplastic syndrome 

Major finding: Median relapse-free survival (RFS) was 2.07 years in the azacitidine group vs. 1.28 years in the control group (P = .19). 

Study details: The data come from a phase 3 open-label randomized trial of 187 patients aged 18 to 75 years with acute myeloid leukemia/myelodysplastic syndrome (AML/MDS); patients received 32 mg/m2 of azacitidine daily for 5 days every 28 days for 12 cycles.

Disclosures: The study was supported by Celgene Pharmaceuticals. Lead author Dr. Oran disclosed serving as a consultant for Celgene and receiving research funding from AROG Pharmaceuticals and Astex Pharmaceuticals.

Source: Oran B et al. Blood Adv. 2020 Nov 10. doi: 10.1182/bloodadvances.2020002544.

Key clinical point: Azacitidine was safe but had no significant impact on relapse-free survival after transplant in in patients with acute myeloid leukemia/myelodysplastic syndrome 

Major finding: Median relapse-free survival (RFS) was 2.07 years in the azacitidine group vs. 1.28 years in the control group (P = .19). 

Study details: The data come from a phase 3 open-label randomized trial of 187 patients aged 18 to 75 years with acute myeloid leukemia/myelodysplastic syndrome (AML/MDS); patients received 32 mg/m2 of azacitidine daily for 5 days every 28 days for 12 cycles.

Disclosures: The study was supported by Celgene Pharmaceuticals. Lead author Dr. Oran disclosed serving as a consultant for Celgene and receiving research funding from AROG Pharmaceuticals and Astex Pharmaceuticals.

Source: Oran B et al. Blood Adv. 2020 Nov 10. doi: 10.1182/bloodadvances.2020002544.

Key clinical point: Imetelstat increased transfusion independence for patients with lower risk myelodysplastic syndromes who were resistant or refractory to treatment with erythropoiesis-stimulating agent.

Major finding: At 8 weeks, 37% of the patients were red blood cell transfusion independent, with an average duration of 65 weeks.

Study details: The data come from a phase II study of 57 adult patients with lower-risk myelodysplastic syndromes dependent on red blood cell transfusion and relapsed or refractory to erythropoiesis-stimulating agent; patients received imetelstat with a primary endpoint of red blood cell transfusion independence at 8 weeks.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Steensma DP et al. J Clin Oncol. 2020 Oct 27. doi: 10.1200/JCO.20.01895. 

Key clinical point: Imetelstat increased transfusion independence for patients with lower risk myelodysplastic syndromes who were resistant or refractory to treatment with erythropoiesis-stimulating agent.

Major finding: At 8 weeks, 37% of the patients were red blood cell transfusion independent, with an average duration of 65 weeks.

Study details: The data come from a phase II study of 57 adult patients with lower-risk myelodysplastic syndromes dependent on red blood cell transfusion and relapsed or refractory to erythropoiesis-stimulating agent; patients received imetelstat with a primary endpoint of red blood cell transfusion independence at 8 weeks.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Steensma DP et al. J Clin Oncol. 2020 Oct 27. doi: 10.1200/JCO.20.01895. 

Key clinical point: Imetelstat increased transfusion independence for patients with lower risk myelodysplastic syndromes who were resistant or refractory to treatment with erythropoiesis-stimulating agent.

Major finding: At 8 weeks, 37% of the patients were red blood cell transfusion independent, with an average duration of 65 weeks.

Study details: The data come from a phase II study of 57 adult patients with lower-risk myelodysplastic syndromes dependent on red blood cell transfusion and relapsed or refractory to erythropoiesis-stimulating agent; patients received imetelstat with a primary endpoint of red blood cell transfusion independence at 8 weeks.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Steensma DP et al. J Clin Oncol. 2020 Oct 27. doi: 10.1200/JCO.20.01895. 

Key clinical point: Food supplements coenzyme Q10 and carnitine significantly improved mitochondrial respiration in patients with low-risk myelodysplastic syndrome

Major finding: A total of 6 patients (21.4%) achieved hematological improvement based on the International Working Group (IWG) response criteria for MDS after 6 months.

Study details: The data come from an open-label study of 33 adults with myelodysplastic syndrome aged 56 to 93 years who received a combination of coenzyme Q10 at 180 mg/day L-carnitine at 2000 mg/ day, and a standard vitamin-mineral complex daily.

Disclosures: The study was supported by the Rising Tide Foundation and Israel Society of Hematology and Blood Transfusion. The researchers had no financial conflicts to disclose.

Source: Filanovsky K et al. Mediterr J Hemtol Infec Dis. 2020 Nov 1. doi: 10.4084/MJHID.2020.072.

Key clinical point: Food supplements coenzyme Q10 and carnitine significantly improved mitochondrial respiration in patients with low-risk myelodysplastic syndrome

Major finding: A total of 6 patients (21.4%) achieved hematological improvement based on the International Working Group (IWG) response criteria for MDS after 6 months.

Study details: The data come from an open-label study of 33 adults with myelodysplastic syndrome aged 56 to 93 years who received a combination of coenzyme Q10 at 180 mg/day L-carnitine at 2000 mg/ day, and a standard vitamin-mineral complex daily.

Disclosures: The study was supported by the Rising Tide Foundation and Israel Society of Hematology and Blood Transfusion. The researchers had no financial conflicts to disclose.

Source: Filanovsky K et al. Mediterr J Hemtol Infec Dis. 2020 Nov 1. doi: 10.4084/MJHID.2020.072.

Key clinical point: Food supplements coenzyme Q10 and carnitine significantly improved mitochondrial respiration in patients with low-risk myelodysplastic syndrome

Major finding: A total of 6 patients (21.4%) achieved hematological improvement based on the International Working Group (IWG) response criteria for MDS after 6 months.

Study details: The data come from an open-label study of 33 adults with myelodysplastic syndrome aged 56 to 93 years who received a combination of coenzyme Q10 at 180 mg/day L-carnitine at 2000 mg/ day, and a standard vitamin-mineral complex daily.

Disclosures: The study was supported by the Rising Tide Foundation and Israel Society of Hematology and Blood Transfusion. The researchers had no financial conflicts to disclose.

Source: Filanovsky K et al. Mediterr J Hemtol Infec Dis. 2020 Nov 1. doi: 10.4084/MJHID.2020.072.

Key clinical point: The financial burden of monthly azacitidine must be weighed against the benefits of treatment, but patients with acute myeloid leukemia and myelodysplastic syndrome have few options.

Major finding: A total of 31 patients with measurable residual disease at baseline were relapse-free and alive after 6 months of monthly injection treatment with azacitidine.

Study details: The data come from a review of the pros and cons of the RELAZA-2, a German-multicentered, open-label, single-arm, phase II study of azacitidine in 53 adult patients who developed measurable residual disease after treatment for acute myeloid leukemia or advanced myelodysplastic syndrome; 29 after chemotherapy and 24 after allogeneic hematopoietic stem cell transplantation (ASCT).

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Pan J et al. Front Oncol. 2020 Oct 22. doi: 10.3389/fonc.2020.576924.

Key clinical point: The financial burden of monthly azacitidine must be weighed against the benefits of treatment, but patients with acute myeloid leukemia and myelodysplastic syndrome have few options.

Major finding: A total of 31 patients with measurable residual disease at baseline were relapse-free and alive after 6 months of monthly injection treatment with azacitidine.

Study details: The data come from a review of the pros and cons of the RELAZA-2, a German-multicentered, open-label, single-arm, phase II study of azacitidine in 53 adult patients who developed measurable residual disease after treatment for acute myeloid leukemia or advanced myelodysplastic syndrome; 29 after chemotherapy and 24 after allogeneic hematopoietic stem cell transplantation (ASCT).

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Pan J et al. Front Oncol. 2020 Oct 22. doi: 10.3389/fonc.2020.576924.

Key clinical point: The financial burden of monthly azacitidine must be weighed against the benefits of treatment, but patients with acute myeloid leukemia and myelodysplastic syndrome have few options.

Major finding: A total of 31 patients with measurable residual disease at baseline were relapse-free and alive after 6 months of monthly injection treatment with azacitidine.

Study details: The data come from a review of the pros and cons of the RELAZA-2, a German-multicentered, open-label, single-arm, phase II study of azacitidine in 53 adult patients who developed measurable residual disease after treatment for acute myeloid leukemia or advanced myelodysplastic syndrome; 29 after chemotherapy and 24 after allogeneic hematopoietic stem cell transplantation (ASCT).

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Pan J et al. Front Oncol. 2020 Oct 22. doi: 10.3389/fonc.2020.576924.

Key clinical point: A novel retinoic acid receptor alpha agonist appeared safe in a phase 1 study of patients with relapsed and refractory high-grade myelodysplastic syndrome or acute myelogenous leukemia.

Major finding: A total of 4 of 11 patients (36%) had stable disease or better after two 28-day treatment cycles; the study ended early because of an inadequate supply of the drug.

Study details: The data come from a phase 1 dose-escalation study of the novel retinoic acid receptor alpha agonist IRX195183; 11 adults aged 18 to 60 years with relapsed or refractory myelodysplastic syndrome or acute myelogenous leukemia received the drug for two 28-day cycles with dosage starting at 50 mg daily or 75 mg daily.

Disclosures: The study was supported by the National Heart, Lung, and Blood Institute, the National Cancer Institute, the Leukemia and Lymphoma Society, and the Augustine Fellowship. IRX195183 was provided by Io Therapeutics, Inc. Lead author Dr. Ambinder had no financial conflicts to disclose. Several coauthors are authors on a patent for the use of IRX195183.

Source: Ambinder AJ et al. Front Oncol. 2020 Oct 23. doi: 10.3389/fonc.2020.587062.

Key clinical point: A novel retinoic acid receptor alpha agonist appeared safe in a phase 1 study of patients with relapsed and refractory high-grade myelodysplastic syndrome or acute myelogenous leukemia.

Major finding: A total of 4 of 11 patients (36%) had stable disease or better after two 28-day treatment cycles; the study ended early because of an inadequate supply of the drug.

Study details: The data come from a phase 1 dose-escalation study of the novel retinoic acid receptor alpha agonist IRX195183; 11 adults aged 18 to 60 years with relapsed or refractory myelodysplastic syndrome or acute myelogenous leukemia received the drug for two 28-day cycles with dosage starting at 50 mg daily or 75 mg daily.

Disclosures: The study was supported by the National Heart, Lung, and Blood Institute, the National Cancer Institute, the Leukemia and Lymphoma Society, and the Augustine Fellowship. IRX195183 was provided by Io Therapeutics, Inc. Lead author Dr. Ambinder had no financial conflicts to disclose. Several coauthors are authors on a patent for the use of IRX195183.

Source: Ambinder AJ et al. Front Oncol. 2020 Oct 23. doi: 10.3389/fonc.2020.587062.

Key clinical point: A novel retinoic acid receptor alpha agonist appeared safe in a phase 1 study of patients with relapsed and refractory high-grade myelodysplastic syndrome or acute myelogenous leukemia.

Major finding: A total of 4 of 11 patients (36%) had stable disease or better after two 28-day treatment cycles; the study ended early because of an inadequate supply of the drug.

Study details: The data come from a phase 1 dose-escalation study of the novel retinoic acid receptor alpha agonist IRX195183; 11 adults aged 18 to 60 years with relapsed or refractory myelodysplastic syndrome or acute myelogenous leukemia received the drug for two 28-day cycles with dosage starting at 50 mg daily or 75 mg daily.

Disclosures: The study was supported by the National Heart, Lung, and Blood Institute, the National Cancer Institute, the Leukemia and Lymphoma Society, and the Augustine Fellowship. IRX195183 was provided by Io Therapeutics, Inc. Lead author Dr. Ambinder had no financial conflicts to disclose. Several coauthors are authors on a patent for the use of IRX195183.

Source: Ambinder AJ et al. Front Oncol. 2020 Oct 23. doi: 10.3389/fonc.2020.587062.

Patients who are profoundly immunosuppressed after extensive cancer treatment, and who fall ill with COVID-19, can shed viable SARS-CoV-2 virus for at least 2 months after symptom onset and may need extended periods of isolation.

Live-virus shedding was detected in 18 patients who had undergone hematopoietic stem cell transplants or chimeric antigen receptor (CAR) T-cell therapy and in 2 patients with lymphoma. 

The finding was reported Dec. 1 in a research letter in the New England Journal of Medicine. 

Individuals who are otherwise healthy when they get COVID-19 are “no longer infectious after the first week of illness,” said lead author Mini Kamboj, MD, chief medical epidemiologist, Memorial Sloan Kettering Cancer Center, New York. 

“We need to keep an open mind about how [much] longer immunocompromised patients could pose an infection risk to others,” she added.

Dr. Kamboj said in an interview that her team’s previous experience with stem cell transplant recipients had suggested that severely immunocompromised patients shed other viruses (such as respiratory syncytial virus, parainfluenza, and influenza) for longer periods of time than do healthy controls.

Based on their latest findings, the investigators suggest that current guidelines for COVID-19 isolation precautions may need to be revised for immunocompromised patients. Even if only a small proportion of patients with cancer who have COVID-19 remain contagious for prolonged periods of time, “it’s a residual risk that we need to address,” Dr. Kamboj said. 

Dr. Kamboj also suggested that physicians follow test-based criteria to determine when a patient undergoing transplant can be released from isolation.
 

Shedding of viable virus

For this study, the investigators used cell cultures to detect viable virus in serially collected nasopharyngeal and sputum samples from 20 immunocompromised patients who had COVID-19 (diagnosed with COVID-19 between March 10 and April 20).  

Patients had lymphoma (n = 8), multiple myeloma (n= 7), acute leukemia/myelodysplastic syndrome (n = 4), and chronic leukemia (n = 1). There were 16 patients who had undergone transplant, 2 who had received CAR T-cell therapy, and 2 who had received other therapy.

There were 15 patients receiving active treatment or chemotherapy, and 11 developed severe COVID-19 infection. 

In total, 78 respiratory samples were collected.

“Viral RNA was detected for up to 78 days after the onset of symptoms,” the researchers reported, “[and] viable virus was detected in 10 of 14 nasopharyngeal samples (71%) that were available from the first day of laboratory testing.”

Five patients were followed up, and from these patients, the team grew virus in culture for up to 61 days after symptom onset. Two among this small group of five patients had received allogenic hematopoietic stem cell transplantation and one patient had been treated with CAR T-cell therapy within the previous 6 months. This patient remained seronegative for antibodies to the coronavirus.

For 11 patients, the team obtained serial sample genomes and found that  “each patient was infected by a distinct virus and there were no major changes in the consensus sequences of the original serial specimens or cultured isolates.” These findings were consistent with persistent infection, they noted.

The authors have disclosed no relevant financial relationships.

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

Patients who are profoundly immunosuppressed after extensive cancer treatment, and who fall ill with COVID-19, can shed viable SARS-CoV-2 virus for at least 2 months after symptom onset and may need extended periods of isolation.

Live-virus shedding was detected in 18 patients who had undergone hematopoietic stem cell transplants or chimeric antigen receptor (CAR) T-cell therapy and in 2 patients with lymphoma. 

The finding was reported Dec. 1 in a research letter in the New England Journal of Medicine. 

Individuals who are otherwise healthy when they get COVID-19 are “no longer infectious after the first week of illness,” said lead author Mini Kamboj, MD, chief medical epidemiologist, Memorial Sloan Kettering Cancer Center, New York. 

“We need to keep an open mind about how [much] longer immunocompromised patients could pose an infection risk to others,” she added.

Dr. Kamboj said in an interview that her team’s previous experience with stem cell transplant recipients had suggested that severely immunocompromised patients shed other viruses (such as respiratory syncytial virus, parainfluenza, and influenza) for longer periods of time than do healthy controls.

Based on their latest findings, the investigators suggest that current guidelines for COVID-19 isolation precautions may need to be revised for immunocompromised patients. Even if only a small proportion of patients with cancer who have COVID-19 remain contagious for prolonged periods of time, “it’s a residual risk that we need to address,” Dr. Kamboj said. 

Dr. Kamboj also suggested that physicians follow test-based criteria to determine when a patient undergoing transplant can be released from isolation.
 

Shedding of viable virus

For this study, the investigators used cell cultures to detect viable virus in serially collected nasopharyngeal and sputum samples from 20 immunocompromised patients who had COVID-19 (diagnosed with COVID-19 between March 10 and April 20).  

Patients had lymphoma (n = 8), multiple myeloma (n= 7), acute leukemia/myelodysplastic syndrome (n = 4), and chronic leukemia (n = 1). There were 16 patients who had undergone transplant, 2 who had received CAR T-cell therapy, and 2 who had received other therapy.

There were 15 patients receiving active treatment or chemotherapy, and 11 developed severe COVID-19 infection. 

In total, 78 respiratory samples were collected.

“Viral RNA was detected for up to 78 days after the onset of symptoms,” the researchers reported, “[and] viable virus was detected in 10 of 14 nasopharyngeal samples (71%) that were available from the first day of laboratory testing.”

Five patients were followed up, and from these patients, the team grew virus in culture for up to 61 days after symptom onset. Two among this small group of five patients had received allogenic hematopoietic stem cell transplantation and one patient had been treated with CAR T-cell therapy within the previous 6 months. This patient remained seronegative for antibodies to the coronavirus.

For 11 patients, the team obtained serial sample genomes and found that  “each patient was infected by a distinct virus and there were no major changes in the consensus sequences of the original serial specimens or cultured isolates.” These findings were consistent with persistent infection, they noted.

The authors have disclosed no relevant financial relationships.

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

Patients who are profoundly immunosuppressed after extensive cancer treatment, and who fall ill with COVID-19, can shed viable SARS-CoV-2 virus for at least 2 months after symptom onset and may need extended periods of isolation.

Live-virus shedding was detected in 18 patients who had undergone hematopoietic stem cell transplants or chimeric antigen receptor (CAR) T-cell therapy and in 2 patients with lymphoma. 

The finding was reported Dec. 1 in a research letter in the New England Journal of Medicine. 

Individuals who are otherwise healthy when they get COVID-19 are “no longer infectious after the first week of illness,” said lead author Mini Kamboj, MD, chief medical epidemiologist, Memorial Sloan Kettering Cancer Center, New York. 

“We need to keep an open mind about how [much] longer immunocompromised patients could pose an infection risk to others,” she added.

Dr. Kamboj said in an interview that her team’s previous experience with stem cell transplant recipients had suggested that severely immunocompromised patients shed other viruses (such as respiratory syncytial virus, parainfluenza, and influenza) for longer periods of time than do healthy controls.

Based on their latest findings, the investigators suggest that current guidelines for COVID-19 isolation precautions may need to be revised for immunocompromised patients. Even if only a small proportion of patients with cancer who have COVID-19 remain contagious for prolonged periods of time, “it’s a residual risk that we need to address,” Dr. Kamboj said. 

Dr. Kamboj also suggested that physicians follow test-based criteria to determine when a patient undergoing transplant can be released from isolation.
 

Shedding of viable virus

For this study, the investigators used cell cultures to detect viable virus in serially collected nasopharyngeal and sputum samples from 20 immunocompromised patients who had COVID-19 (diagnosed with COVID-19 between March 10 and April 20).  

Patients had lymphoma (n = 8), multiple myeloma (n= 7), acute leukemia/myelodysplastic syndrome (n = 4), and chronic leukemia (n = 1). There were 16 patients who had undergone transplant, 2 who had received CAR T-cell therapy, and 2 who had received other therapy.

There were 15 patients receiving active treatment or chemotherapy, and 11 developed severe COVID-19 infection. 

In total, 78 respiratory samples were collected.

“Viral RNA was detected for up to 78 days after the onset of symptoms,” the researchers reported, “[and] viable virus was detected in 10 of 14 nasopharyngeal samples (71%) that were available from the first day of laboratory testing.”

Five patients were followed up, and from these patients, the team grew virus in culture for up to 61 days after symptom onset. Two among this small group of five patients had received allogenic hematopoietic stem cell transplantation and one patient had been treated with CAR T-cell therapy within the previous 6 months. This patient remained seronegative for antibodies to the coronavirus.

For 11 patients, the team obtained serial sample genomes and found that  “each patient was infected by a distinct virus and there were no major changes in the consensus sequences of the original serial specimens or cultured isolates.” These findings were consistent with persistent infection, they noted.

The authors have disclosed no relevant financial relationships.

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

New results suggest that allogeneic hematopoietic cell transplantation (HCT), which is typically reserved for younger patients, may well be offered to older patients with advanced myelodysplastic syndrome (MDS).

In patients with a median age of 66 years who had received a donor transplant, the overall survival (OS) at 3 years was almost double compared with patients who did not receive a transplant – 47.9% vs. 26.6% for the “no-donor” group.  

The finding comes from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Study 1102 (NCT02016781) presented at the American Society of Hematology (ASH) 2020 virtual meeting.

“This study conclusively solidifies the role of transplantation in older individuals with MDS,” presenter Corey Cutler, MD, MPH, of the Dana-Farber Cancer Center, Boston, said in an interview.

Coauthor Ryotaro Nakamura, MD, of City of Hope, Duarte, Calif., said in an interview that this was the largest and first trial in the United States to determine in a prospective fashion that allogeneic stem cell transplantation offers a significant survival in older patients. “There was more than a 20% benefit in OS in this age group,” he said.

“This is an incredibly important study,” said Andrew Brunner, MD, medical oncologist at the Mass General Cancer Center in Boston, who was approached for comment. He explained that for years early transplant was recommended as important for patients who have higher-risk MDS. “This study validates this in a prospective, pseudo-randomized (donor/no donor) fashion,” he said in an interview.

“[This study] is really a seminal advance in the care of patients with MDS. Transplant should be integrated into the care algorithm, if not already, and we as a community need to build upon this study further,” Dr. Brunner added.

Several experts in addition to the authors hailed the study as practice changing.

Robert A. Brodsky, MD, ASH, director of the division of hematology at Johns Hopkins University, Baltimore, noted that in younger patients bone marrow transplant is the standard of care for aggressive MDS, but a lot of practices do not refer older patients or those with comorbidities for transplant and prefer to give these patients palliative care with hypomethylating agents for fear that the transplant process would be too toxic.

“There has been an institutional bias to do transplant in older patients, but until now there was no randomized clinical trial to show that this is the right choice. Now we have the data,” Dr Brodsky said, predicting that “this study will change the standard of care.”

Henry Fung, MD, chair of the department of bone marrow transplant and cellular therapies at Fox Chase Cancer Center, Philadelphia, agreed. “We should congratulate all the investigators and our patients who participated in this study. Reduced intensity allogeneic stem cell transplantation improved disease control and overall survival with similar quality of life.

“I will recommend all patients with intermediate-2 or higher-risk MDS to be evaluated by the transplant team at diagnosis and eligible patients should be considered for a transplant,” Dr. Fung said in an interview.

Immediate impact on clinical practice

Lead author Dr. Cutler suggested that the study results had an immediate impact for changing clinical practice. “Individuals between the ages of 50 and 75 years with intermediate-2 or high-risk MDS who are eligible to undergo reduced-intensity transplantation had superior outcomes if they had a suitable donor for transplantation in comparison with those who did not have a donor,” he said.

Dr. Cutler further explained that many community-based hematologists do not refer their patients for transplantation. In addition, there is a lack of a uniform payer position for transplantation for MDS, he noted. Also, there is a lack of understanding of the cost-effectiveness of transplantation in comparison to nontransplant strategies, he suggested.

“Transplant is curative for MDS,” he emphasized. Most transplant recipients will eventually become transfusion-independent within weeks to months from transplant.

“We do transplants in this age group all the time,” Dr. Cutler noted. He said that academic centers will continue to offer transplants, and suggested that community oncologists encourage referral to transplant centers early in a patient’s disease course to maximize search time and provide patients all potential options for therapy.

Dr. Brunner agreed and noted that there is a need to build capacity for higher transplant volume, and in general physicians should seek ways to expand this treatment option to more patients. “At this time, allogeneic transplant still requires close collaboration with referral centers; that said, more and more we are able to work closely with colleagues in the community to share management, including earlier after the actual transplant,” he said.

He noted that one silver lining of the pandemic in 2020 has been increased use of telemedicine to collaborate. “Ongoing advances may be able to further encourage these virtual connections to enhance the entire patient care experience,” Dr. Brunner said.
 

Reimbursement by CMS for Medicare recipients

Despite the data showing benefit, allogeneic stem cell transplantation is not offered to older individuals with high-risk MDS and is not covered by Medicare in the United States, Dr. Cutler noted in his presentation.

“This study was spurred by the CMS [Centers for Medicare & Medicaid Services] ruling for transplantation in MDS and the story has come full circle,” Aaron T. Gerds, MD, MS, noted at a preconference press briefing. Dr. Gerds is chair of the ASH Committee on Communications and assistant professor at the Cleveland Clinic Taussig Cancer Institute, Cleveland.

Dr. Nakamura explained that in 2010 a CMS decision memo noted that the evidence of a benefit for transplantation in MDS was lacking and Medicare would not cover transplant unless patients were enrolled in a clinical study. That memo outlined criteria that a clinical trial would have to address before it could consider reimbursement for Medicare beneficiaries.

“The BMT CTN Study 1102 was one of two studies that met the criteria set by CMS,” Dr. Nakamura said, noting that the data are being prepared for CMS review.

“This study will likely be the deciding factor for CMS to begin to cover payment for transplantation for MDS,” said Dr. Cutler.

The other study, published earlier this year in JAMA Oncology, showed that outcomes for patients older than ager 65 were similar to those of patients aged 55-65.
 

BMT CTN 1102 study details

Dr. Cutler noted that the study was designed to address the issue of whether transplantation was beneficial to Medicare-aged individuals with high-risk MDS, and the trial had been approved by Medicare.

The multicenter study enrolled patients who were between ages 50 and 75 years and had newly diagnosed MDS of higher risk (International Prognostic Scoring System [IPSS] intermediate-2 or higher) and were candidates for reduced intensity conditioning (RIC) allogeneic HCT.

Patients were enrolled prior to a formal donor search and were initially assigned to the “no donor” group and reassigned to the donor group when a suitable donor (matched sibling or unrelated donor) was identified. Patients underwent RIC HCT according to institution protocol.

Of 384 patients, 260 received RIC HCT and 124 received hypomethylating therapy. Median follow-up was 34.2 months for the donor group and 26.9 months for the no-donor group.

The two arms were well balanced with respect to age (median 66 years), gender, disease risk [two-thirds of the patients had an intermediate-2 and one third had a high-risk MDS], and response to hypomethylating therapy. The majority of subjects in the donor arm had unrelated donors and more than one-third had a high comorbidity score, Dr. Cutler indicated.

At 3 years, absolute improvement in OS was 21.3% in favor of donor-arm subjects. Leukemia-free survival was also higher in the donor group: 35.8% vs. 20.6% for the no-donor group.

Improvement in OS for patients receiving transplants was seen across all patient subtypes, regardless of age, response to hypomethylating therapy, and IPSS score. “Treatment effects were seen in any subgroup, but particularly in subjects above age 65,” Dr. Cutler stressed.

In an as-treated analysis that excluded subjects who died, the treatment effects were even more pronounced, with an absolute improvement in OS of 31.4% (47.4% vs. 16% for the no-donor arm) and improvement in leukemia-free survival of 28.4% (39.3% vs. 10.9% for the no-donor arm).

In 25 patients in the no-donor arm who subsequently went on to receive alternate donor transplant, the 3-year OS and leukemia-free survival was 58.5%, underscoring the potential value of alternate donor transplant, Dr. Cutler noted.

Dr. Nakamura emphasized that the gains in survival benefits were not seen at the expense of quality of life, as preliminary results showed no difference in quality-of-life measures across those who received donor transplants and those who did not.

Dr. Brunner noted that physicians often highlight the toxicities of transplant as a consideration for whether to proceed, and while there are toxicities specific to transplant that should be considered, in this study it is seen that, even early on, survival is improved in those patients who move toward early transplant. “It also underscores the limitations of current nontransplant treatments for MDS – there is much room to improve,” he said.
 

Role for alternate donors

Dr. Cutler noted that the majority of patients in the no-donor group died without transplantation. “We need to establish the role of alternative donor transplantation in this population,” he said. Dr. Nakamura indicated that mismatched donors and haploidentical donors such as family donors and umbilical cord blood may be alternate donor sources; outcomes from published studies show similar results, he said.

However, Dr. Brunner noted that the study looked only at traditional fully matched donors, leaving open some questions about alternative donor options such as haploidentical donors and umbilical cord blood donation.

“Our experience in other areas of transplant would suggest that these donor sources may be as good as traditional fully matched options, when using newer conditioning and prophylaxis regimens,” Dr. Brunner said.

Dr. Cutler added, “With the increased acceptance of alternate transplant modalities, we need to determine the outcomes associated with these in prospective trials.”

“I think a significant consideration here as well is health equity,” Dr. Brunner said. “Donor options vary according to race and ethnicity and we need to be proactive as a community to ensure that all MDS patients have access to a potentially curative option early in their diagnosis.”

Dr. Cutler reports consultancy for Mesoblast, Generon, Medsenic, Jazz, Kadmon, and Incyte. Dr. Nakamura reports relationships with Magenta Therapeutics, Kyowa-Kirin, Alexion, Merck, NapaJen Pharma, Kadmon Corporation, Celgene, and Viracor. Dr. Fung has disclosed no relevant financial relationships. Dr. Brodsky reports receiving funding from and being on the board/advisory committee for Achillion Pharmaceuticals, consults with Alexion Pharmaceuticals, and receives honoraria from UpToDate. Dr. Brunner reports relationships with Biogen, Acceleron Pharma Inc, Celgene/BMS, Forty Seven Inc, Jazz Pharma, Novartis, Takeda, Xcenda, GSK, Janssen, and AstraZeneca.

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

New results suggest that allogeneic hematopoietic cell transplantation (HCT), which is typically reserved for younger patients, may well be offered to older patients with advanced myelodysplastic syndrome (MDS).

In patients with a median age of 66 years who had received a donor transplant, the overall survival (OS) at 3 years was almost double compared with patients who did not receive a transplant – 47.9% vs. 26.6% for the “no-donor” group.  

The finding comes from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Study 1102 (NCT02016781) presented at the American Society of Hematology (ASH) 2020 virtual meeting.

“This study conclusively solidifies the role of transplantation in older individuals with MDS,” presenter Corey Cutler, MD, MPH, of the Dana-Farber Cancer Center, Boston, said in an interview.

Coauthor Ryotaro Nakamura, MD, of City of Hope, Duarte, Calif., said in an interview that this was the largest and first trial in the United States to determine in a prospective fashion that allogeneic stem cell transplantation offers a significant survival in older patients. “There was more than a 20% benefit in OS in this age group,” he said.

“This is an incredibly important study,” said Andrew Brunner, MD, medical oncologist at the Mass General Cancer Center in Boston, who was approached for comment. He explained that for years early transplant was recommended as important for patients who have higher-risk MDS. “This study validates this in a prospective, pseudo-randomized (donor/no donor) fashion,” he said in an interview.

“[This study] is really a seminal advance in the care of patients with MDS. Transplant should be integrated into the care algorithm, if not already, and we as a community need to build upon this study further,” Dr. Brunner added.

Several experts in addition to the authors hailed the study as practice changing.

Robert A. Brodsky, MD, ASH, director of the division of hematology at Johns Hopkins University, Baltimore, noted that in younger patients bone marrow transplant is the standard of care for aggressive MDS, but a lot of practices do not refer older patients or those with comorbidities for transplant and prefer to give these patients palliative care with hypomethylating agents for fear that the transplant process would be too toxic.

“There has been an institutional bias to do transplant in older patients, but until now there was no randomized clinical trial to show that this is the right choice. Now we have the data,” Dr Brodsky said, predicting that “this study will change the standard of care.”

Henry Fung, MD, chair of the department of bone marrow transplant and cellular therapies at Fox Chase Cancer Center, Philadelphia, agreed. “We should congratulate all the investigators and our patients who participated in this study. Reduced intensity allogeneic stem cell transplantation improved disease control and overall survival with similar quality of life.

“I will recommend all patients with intermediate-2 or higher-risk MDS to be evaluated by the transplant team at diagnosis and eligible patients should be considered for a transplant,” Dr. Fung said in an interview.

Immediate impact on clinical practice

Lead author Dr. Cutler suggested that the study results had an immediate impact for changing clinical practice. “Individuals between the ages of 50 and 75 years with intermediate-2 or high-risk MDS who are eligible to undergo reduced-intensity transplantation had superior outcomes if they had a suitable donor for transplantation in comparison with those who did not have a donor,” he said.

Dr. Cutler further explained that many community-based hematologists do not refer their patients for transplantation. In addition, there is a lack of a uniform payer position for transplantation for MDS, he noted. Also, there is a lack of understanding of the cost-effectiveness of transplantation in comparison to nontransplant strategies, he suggested.

“Transplant is curative for MDS,” he emphasized. Most transplant recipients will eventually become transfusion-independent within weeks to months from transplant.

“We do transplants in this age group all the time,” Dr. Cutler noted. He said that academic centers will continue to offer transplants, and suggested that community oncologists encourage referral to transplant centers early in a patient’s disease course to maximize search time and provide patients all potential options for therapy.

Dr. Brunner agreed and noted that there is a need to build capacity for higher transplant volume, and in general physicians should seek ways to expand this treatment option to more patients. “At this time, allogeneic transplant still requires close collaboration with referral centers; that said, more and more we are able to work closely with colleagues in the community to share management, including earlier after the actual transplant,” he said.

He noted that one silver lining of the pandemic in 2020 has been increased use of telemedicine to collaborate. “Ongoing advances may be able to further encourage these virtual connections to enhance the entire patient care experience,” Dr. Brunner said.
 

Reimbursement by CMS for Medicare recipients

Despite the data showing benefit, allogeneic stem cell transplantation is not offered to older individuals with high-risk MDS and is not covered by Medicare in the United States, Dr. Cutler noted in his presentation.

“This study was spurred by the CMS [Centers for Medicare & Medicaid Services] ruling for transplantation in MDS and the story has come full circle,” Aaron T. Gerds, MD, MS, noted at a preconference press briefing. Dr. Gerds is chair of the ASH Committee on Communications and assistant professor at the Cleveland Clinic Taussig Cancer Institute, Cleveland.

Dr. Nakamura explained that in 2010 a CMS decision memo noted that the evidence of a benefit for transplantation in MDS was lacking and Medicare would not cover transplant unless patients were enrolled in a clinical study. That memo outlined criteria that a clinical trial would have to address before it could consider reimbursement for Medicare beneficiaries.

“The BMT CTN Study 1102 was one of two studies that met the criteria set by CMS,” Dr. Nakamura said, noting that the data are being prepared for CMS review.

“This study will likely be the deciding factor for CMS to begin to cover payment for transplantation for MDS,” said Dr. Cutler.

The other study, published earlier this year in JAMA Oncology, showed that outcomes for patients older than ager 65 were similar to those of patients aged 55-65.
 

BMT CTN 1102 study details

Dr. Cutler noted that the study was designed to address the issue of whether transplantation was beneficial to Medicare-aged individuals with high-risk MDS, and the trial had been approved by Medicare.

The multicenter study enrolled patients who were between ages 50 and 75 years and had newly diagnosed MDS of higher risk (International Prognostic Scoring System [IPSS] intermediate-2 or higher) and were candidates for reduced intensity conditioning (RIC) allogeneic HCT.

Patients were enrolled prior to a formal donor search and were initially assigned to the “no donor” group and reassigned to the donor group when a suitable donor (matched sibling or unrelated donor) was identified. Patients underwent RIC HCT according to institution protocol.

Of 384 patients, 260 received RIC HCT and 124 received hypomethylating therapy. Median follow-up was 34.2 months for the donor group and 26.9 months for the no-donor group.

The two arms were well balanced with respect to age (median 66 years), gender, disease risk [two-thirds of the patients had an intermediate-2 and one third had a high-risk MDS], and response to hypomethylating therapy. The majority of subjects in the donor arm had unrelated donors and more than one-third had a high comorbidity score, Dr. Cutler indicated.

At 3 years, absolute improvement in OS was 21.3% in favor of donor-arm subjects. Leukemia-free survival was also higher in the donor group: 35.8% vs. 20.6% for the no-donor group.

Improvement in OS for patients receiving transplants was seen across all patient subtypes, regardless of age, response to hypomethylating therapy, and IPSS score. “Treatment effects were seen in any subgroup, but particularly in subjects above age 65,” Dr. Cutler stressed.

In an as-treated analysis that excluded subjects who died, the treatment effects were even more pronounced, with an absolute improvement in OS of 31.4% (47.4% vs. 16% for the no-donor arm) and improvement in leukemia-free survival of 28.4% (39.3% vs. 10.9% for the no-donor arm).

In 25 patients in the no-donor arm who subsequently went on to receive alternate donor transplant, the 3-year OS and leukemia-free survival was 58.5%, underscoring the potential value of alternate donor transplant, Dr. Cutler noted.

Dr. Nakamura emphasized that the gains in survival benefits were not seen at the expense of quality of life, as preliminary results showed no difference in quality-of-life measures across those who received donor transplants and those who did not.

Dr. Brunner noted that physicians often highlight the toxicities of transplant as a consideration for whether to proceed, and while there are toxicities specific to transplant that should be considered, in this study it is seen that, even early on, survival is improved in those patients who move toward early transplant. “It also underscores the limitations of current nontransplant treatments for MDS – there is much room to improve,” he said.
 

Role for alternate donors

Dr. Cutler noted that the majority of patients in the no-donor group died without transplantation. “We need to establish the role of alternative donor transplantation in this population,” he said. Dr. Nakamura indicated that mismatched donors and haploidentical donors such as family donors and umbilical cord blood may be alternate donor sources; outcomes from published studies show similar results, he said.

However, Dr. Brunner noted that the study looked only at traditional fully matched donors, leaving open some questions about alternative donor options such as haploidentical donors and umbilical cord blood donation.

“Our experience in other areas of transplant would suggest that these donor sources may be as good as traditional fully matched options, when using newer conditioning and prophylaxis regimens,” Dr. Brunner said.

Dr. Cutler added, “With the increased acceptance of alternate transplant modalities, we need to determine the outcomes associated with these in prospective trials.”

“I think a significant consideration here as well is health equity,” Dr. Brunner said. “Donor options vary according to race and ethnicity and we need to be proactive as a community to ensure that all MDS patients have access to a potentially curative option early in their diagnosis.”

Dr. Cutler reports consultancy for Mesoblast, Generon, Medsenic, Jazz, Kadmon, and Incyte. Dr. Nakamura reports relationships with Magenta Therapeutics, Kyowa-Kirin, Alexion, Merck, NapaJen Pharma, Kadmon Corporation, Celgene, and Viracor. Dr. Fung has disclosed no relevant financial relationships. Dr. Brodsky reports receiving funding from and being on the board/advisory committee for Achillion Pharmaceuticals, consults with Alexion Pharmaceuticals, and receives honoraria from UpToDate. Dr. Brunner reports relationships with Biogen, Acceleron Pharma Inc, Celgene/BMS, Forty Seven Inc, Jazz Pharma, Novartis, Takeda, Xcenda, GSK, Janssen, and AstraZeneca.

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

New results suggest that allogeneic hematopoietic cell transplantation (HCT), which is typically reserved for younger patients, may well be offered to older patients with advanced myelodysplastic syndrome (MDS).

In patients with a median age of 66 years who had received a donor transplant, the overall survival (OS) at 3 years was almost double compared with patients who did not receive a transplant – 47.9% vs. 26.6% for the “no-donor” group.  

The finding comes from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Study 1102 (NCT02016781) presented at the American Society of Hematology (ASH) 2020 virtual meeting.

“This study conclusively solidifies the role of transplantation in older individuals with MDS,” presenter Corey Cutler, MD, MPH, of the Dana-Farber Cancer Center, Boston, said in an interview.

Coauthor Ryotaro Nakamura, MD, of City of Hope, Duarte, Calif., said in an interview that this was the largest and first trial in the United States to determine in a prospective fashion that allogeneic stem cell transplantation offers a significant survival in older patients. “There was more than a 20% benefit in OS in this age group,” he said.

“This is an incredibly important study,” said Andrew Brunner, MD, medical oncologist at the Mass General Cancer Center in Boston, who was approached for comment. He explained that for years early transplant was recommended as important for patients who have higher-risk MDS. “This study validates this in a prospective, pseudo-randomized (donor/no donor) fashion,” he said in an interview.

“[This study] is really a seminal advance in the care of patients with MDS. Transplant should be integrated into the care algorithm, if not already, and we as a community need to build upon this study further,” Dr. Brunner added.

Several experts in addition to the authors hailed the study as practice changing.

Robert A. Brodsky, MD, ASH, director of the division of hematology at Johns Hopkins University, Baltimore, noted that in younger patients bone marrow transplant is the standard of care for aggressive MDS, but a lot of practices do not refer older patients or those with comorbidities for transplant and prefer to give these patients palliative care with hypomethylating agents for fear that the transplant process would be too toxic.

“There has been an institutional bias to do transplant in older patients, but until now there was no randomized clinical trial to show that this is the right choice. Now we have the data,” Dr Brodsky said, predicting that “this study will change the standard of care.”

Henry Fung, MD, chair of the department of bone marrow transplant and cellular therapies at Fox Chase Cancer Center, Philadelphia, agreed. “We should congratulate all the investigators and our patients who participated in this study. Reduced intensity allogeneic stem cell transplantation improved disease control and overall survival with similar quality of life.

“I will recommend all patients with intermediate-2 or higher-risk MDS to be evaluated by the transplant team at diagnosis and eligible patients should be considered for a transplant,” Dr. Fung said in an interview.

Immediate impact on clinical practice

Lead author Dr. Cutler suggested that the study results had an immediate impact for changing clinical practice. “Individuals between the ages of 50 and 75 years with intermediate-2 or high-risk MDS who are eligible to undergo reduced-intensity transplantation had superior outcomes if they had a suitable donor for transplantation in comparison with those who did not have a donor,” he said.

Dr. Cutler further explained that many community-based hematologists do not refer their patients for transplantation. In addition, there is a lack of a uniform payer position for transplantation for MDS, he noted. Also, there is a lack of understanding of the cost-effectiveness of transplantation in comparison to nontransplant strategies, he suggested.

“Transplant is curative for MDS,” he emphasized. Most transplant recipients will eventually become transfusion-independent within weeks to months from transplant.

“We do transplants in this age group all the time,” Dr. Cutler noted. He said that academic centers will continue to offer transplants, and suggested that community oncologists encourage referral to transplant centers early in a patient’s disease course to maximize search time and provide patients all potential options for therapy.

Dr. Brunner agreed and noted that there is a need to build capacity for higher transplant volume, and in general physicians should seek ways to expand this treatment option to more patients. “At this time, allogeneic transplant still requires close collaboration with referral centers; that said, more and more we are able to work closely with colleagues in the community to share management, including earlier after the actual transplant,” he said.

He noted that one silver lining of the pandemic in 2020 has been increased use of telemedicine to collaborate. “Ongoing advances may be able to further encourage these virtual connections to enhance the entire patient care experience,” Dr. Brunner said.
 

Reimbursement by CMS for Medicare recipients

Despite the data showing benefit, allogeneic stem cell transplantation is not offered to older individuals with high-risk MDS and is not covered by Medicare in the United States, Dr. Cutler noted in his presentation.

“This study was spurred by the CMS [Centers for Medicare & Medicaid Services] ruling for transplantation in MDS and the story has come full circle,” Aaron T. Gerds, MD, MS, noted at a preconference press briefing. Dr. Gerds is chair of the ASH Committee on Communications and assistant professor at the Cleveland Clinic Taussig Cancer Institute, Cleveland.

Dr. Nakamura explained that in 2010 a CMS decision memo noted that the evidence of a benefit for transplantation in MDS was lacking and Medicare would not cover transplant unless patients were enrolled in a clinical study. That memo outlined criteria that a clinical trial would have to address before it could consider reimbursement for Medicare beneficiaries.

“The BMT CTN Study 1102 was one of two studies that met the criteria set by CMS,” Dr. Nakamura said, noting that the data are being prepared for CMS review.

“This study will likely be the deciding factor for CMS to begin to cover payment for transplantation for MDS,” said Dr. Cutler.

The other study, published earlier this year in JAMA Oncology, showed that outcomes for patients older than ager 65 were similar to those of patients aged 55-65.
 

BMT CTN 1102 study details

Dr. Cutler noted that the study was designed to address the issue of whether transplantation was beneficial to Medicare-aged individuals with high-risk MDS, and the trial had been approved by Medicare.

The multicenter study enrolled patients who were between ages 50 and 75 years and had newly diagnosed MDS of higher risk (International Prognostic Scoring System [IPSS] intermediate-2 or higher) and were candidates for reduced intensity conditioning (RIC) allogeneic HCT.

Patients were enrolled prior to a formal donor search and were initially assigned to the “no donor” group and reassigned to the donor group when a suitable donor (matched sibling or unrelated donor) was identified. Patients underwent RIC HCT according to institution protocol.

Of 384 patients, 260 received RIC HCT and 124 received hypomethylating therapy. Median follow-up was 34.2 months for the donor group and 26.9 months for the no-donor group.

The two arms were well balanced with respect to age (median 66 years), gender, disease risk [two-thirds of the patients had an intermediate-2 and one third had a high-risk MDS], and response to hypomethylating therapy. The majority of subjects in the donor arm had unrelated donors and more than one-third had a high comorbidity score, Dr. Cutler indicated.

At 3 years, absolute improvement in OS was 21.3% in favor of donor-arm subjects. Leukemia-free survival was also higher in the donor group: 35.8% vs. 20.6% for the no-donor group.

Improvement in OS for patients receiving transplants was seen across all patient subtypes, regardless of age, response to hypomethylating therapy, and IPSS score. “Treatment effects were seen in any subgroup, but particularly in subjects above age 65,” Dr. Cutler stressed.

In an as-treated analysis that excluded subjects who died, the treatment effects were even more pronounced, with an absolute improvement in OS of 31.4% (47.4% vs. 16% for the no-donor arm) and improvement in leukemia-free survival of 28.4% (39.3% vs. 10.9% for the no-donor arm).

In 25 patients in the no-donor arm who subsequently went on to receive alternate donor transplant, the 3-year OS and leukemia-free survival was 58.5%, underscoring the potential value of alternate donor transplant, Dr. Cutler noted.

Dr. Nakamura emphasized that the gains in survival benefits were not seen at the expense of quality of life, as preliminary results showed no difference in quality-of-life measures across those who received donor transplants and those who did not.

Dr. Brunner noted that physicians often highlight the toxicities of transplant as a consideration for whether to proceed, and while there are toxicities specific to transplant that should be considered, in this study it is seen that, even early on, survival is improved in those patients who move toward early transplant. “It also underscores the limitations of current nontransplant treatments for MDS – there is much room to improve,” he said.
 

Role for alternate donors

Dr. Cutler noted that the majority of patients in the no-donor group died without transplantation. “We need to establish the role of alternative donor transplantation in this population,” he said. Dr. Nakamura indicated that mismatched donors and haploidentical donors such as family donors and umbilical cord blood may be alternate donor sources; outcomes from published studies show similar results, he said.

However, Dr. Brunner noted that the study looked only at traditional fully matched donors, leaving open some questions about alternative donor options such as haploidentical donors and umbilical cord blood donation.

“Our experience in other areas of transplant would suggest that these donor sources may be as good as traditional fully matched options, when using newer conditioning and prophylaxis regimens,” Dr. Brunner said.

Dr. Cutler added, “With the increased acceptance of alternate transplant modalities, we need to determine the outcomes associated with these in prospective trials.”

“I think a significant consideration here as well is health equity,” Dr. Brunner said. “Donor options vary according to race and ethnicity and we need to be proactive as a community to ensure that all MDS patients have access to a potentially curative option early in their diagnosis.”

Dr. Cutler reports consultancy for Mesoblast, Generon, Medsenic, Jazz, Kadmon, and Incyte. Dr. Nakamura reports relationships with Magenta Therapeutics, Kyowa-Kirin, Alexion, Merck, NapaJen Pharma, Kadmon Corporation, Celgene, and Viracor. Dr. Fung has disclosed no relevant financial relationships. Dr. Brodsky reports receiving funding from and being on the board/advisory committee for Achillion Pharmaceuticals, consults with Alexion Pharmaceuticals, and receives honoraria from UpToDate. Dr. Brunner reports relationships with Biogen, Acceleron Pharma Inc, Celgene/BMS, Forty Seven Inc, Jazz Pharma, Novartis, Takeda, Xcenda, GSK, Janssen, and AstraZeneca.

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

The current COVID-19 pandemic has afflicted over 44 million individuals across the planet and been responsible for over 1 million deaths, particularly in high-risk populations. As a result of the overall advanced age, frailty and pre-existing comorbidities of patients with MDS, SARS-Cov2 was feared to be particularly dangerous in this patient population. A recent study by Mossuto et al describes the outcomes of patients with MDS with SARS-CoV-2 infection during the Coronavirus outbreak in Italy. Among a total of 5326 patients with MDS followed during the study period, 63 (1.18%) had confirmed SARS-CoV-2 infection. With a median age of 73 years, the mortality rate among these patients was 52% compared to that of the non-MDS population (24%), and was particularly high on male MDS patients (73% of total deaths). Respiratory failure was the cause of death in all the MDS patients with ARDS in 50% of deceased patients, and with majority of patients who were able to recover having lower risk IPSS-R categories. Interestingly, no differences in mortality or severity of infection were observed based on the type of therapy received for their MDS. These findings are not surprising given the underlying inflammation and immunosuppression in patients with MDS. Until the development of COVID-19 vaccines has been completed, identification of high-risk populations and specific guidelines for the management of SARS-CoV-2 infection in patients with MDS remains of paramount importance.

Clonal hematopoiesis is a known cardiovascular risk factor which has been associated with increased risk of cardiac and cerebrovascular events. Recent studies have also associated MDS with higher than expected cardiovascular comorbidities and cardiovascular-related deaths. In accordance to prior publications by Naqvi et al, a recent study by Faber et al retrospectively evaluated 236 MDS patients and studied the associations of somatic mutations with cardiovascular risk. Overall, the authors observed that 27% of patients in their study population developed vascular event, and that ASXL1 mutations were predictive of vascular disease by multivariate analysis (with an odds ratio of 4.2). This data further supports the biological connection between comorbidities and hematopoietic clonal disorders, the role of inflammaging and the need to maximize cardiovascular risk factor care in patients with MDS and develop specific therapies targeting both the disease biology and the underlying mechanisms leading to increased cardiovascular risk.

Guillermo Montalban Bravo, MD
Assistant Professor, Department of Leukemia, Division of Cancer Medicine
MD Anderson Cancer Center, Houston, TX

The current COVID-19 pandemic has afflicted over 44 million individuals across the planet and been responsible for over 1 million deaths, particularly in high-risk populations. As a result of the overall advanced age, frailty and pre-existing comorbidities of patients with MDS, SARS-Cov2 was feared to be particularly dangerous in this patient population. A recent study by Mossuto et al describes the outcomes of patients with MDS with SARS-CoV-2 infection during the Coronavirus outbreak in Italy. Among a total of 5326 patients with MDS followed during the study period, 63 (1.18%) had confirmed SARS-CoV-2 infection. With a median age of 73 years, the mortality rate among these patients was 52% compared to that of the non-MDS population (24%), and was particularly high on male MDS patients (73% of total deaths). Respiratory failure was the cause of death in all the MDS patients with ARDS in 50% of deceased patients, and with majority of patients who were able to recover having lower risk IPSS-R categories. Interestingly, no differences in mortality or severity of infection were observed based on the type of therapy received for their MDS. These findings are not surprising given the underlying inflammation and immunosuppression in patients with MDS. Until the development of COVID-19 vaccines has been completed, identification of high-risk populations and specific guidelines for the management of SARS-CoV-2 infection in patients with MDS remains of paramount importance.

Clonal hematopoiesis is a known cardiovascular risk factor which has been associated with increased risk of cardiac and cerebrovascular events. Recent studies have also associated MDS with higher than expected cardiovascular comorbidities and cardiovascular-related deaths. In accordance to prior publications by Naqvi et al, a recent study by Faber et al retrospectively evaluated 236 MDS patients and studied the associations of somatic mutations with cardiovascular risk. Overall, the authors observed that 27% of patients in their study population developed vascular event, and that ASXL1 mutations were predictive of vascular disease by multivariate analysis (with an odds ratio of 4.2). This data further supports the biological connection between comorbidities and hematopoietic clonal disorders, the role of inflammaging and the need to maximize cardiovascular risk factor care in patients with MDS and develop specific therapies targeting both the disease biology and the underlying mechanisms leading to increased cardiovascular risk.

Guillermo Montalban Bravo, MD
Assistant Professor, Department of Leukemia, Division of Cancer Medicine
MD Anderson Cancer Center, Houston, TX

The current COVID-19 pandemic has afflicted over 44 million individuals across the planet and been responsible for over 1 million deaths, particularly in high-risk populations. As a result of the overall advanced age, frailty and pre-existing comorbidities of patients with MDS, SARS-Cov2 was feared to be particularly dangerous in this patient population. A recent study by Mossuto et al describes the outcomes of patients with MDS with SARS-CoV-2 infection during the Coronavirus outbreak in Italy. Among a total of 5326 patients with MDS followed during the study period, 63 (1.18%) had confirmed SARS-CoV-2 infection. With a median age of 73 years, the mortality rate among these patients was 52% compared to that of the non-MDS population (24%), and was particularly high on male MDS patients (73% of total deaths). Respiratory failure was the cause of death in all the MDS patients with ARDS in 50% of deceased patients, and with majority of patients who were able to recover having lower risk IPSS-R categories. Interestingly, no differences in mortality or severity of infection were observed based on the type of therapy received for their MDS. These findings are not surprising given the underlying inflammation and immunosuppression in patients with MDS. Until the development of COVID-19 vaccines has been completed, identification of high-risk populations and specific guidelines for the management of SARS-CoV-2 infection in patients with MDS remains of paramount importance.

Clonal hematopoiesis is a known cardiovascular risk factor which has been associated with increased risk of cardiac and cerebrovascular events. Recent studies have also associated MDS with higher than expected cardiovascular comorbidities and cardiovascular-related deaths. In accordance to prior publications by Naqvi et al, a recent study by Faber et al retrospectively evaluated 236 MDS patients and studied the associations of somatic mutations with cardiovascular risk. Overall, the authors observed that 27% of patients in their study population developed vascular event, and that ASXL1 mutations were predictive of vascular disease by multivariate analysis (with an odds ratio of 4.2). This data further supports the biological connection between comorbidities and hematopoietic clonal disorders, the role of inflammaging and the need to maximize cardiovascular risk factor care in patients with MDS and develop specific therapies targeting both the disease biology and the underlying mechanisms leading to increased cardiovascular risk.

Guillermo Montalban Bravo, MD
Assistant Professor, Department of Leukemia, Division of Cancer Medicine
MD Anderson Cancer Center, Houston, TX

Key clinical point: Gene mutations involving ASXL1 were significantly associated with increased risk of vascular events in adults with myelodysplastic syndrome, but Trisomy 8 appeared to have a protective effect.

Major finding: Overall, the incidence of vascular disease in the study population was 27%; mutations in the ASXL1 in particular were significant predictors of vascular disease in multivariate analysis (odds ratio 4.2); however, both elevated ferritin and Trisomy 8 were significantly associated with a lower risk of vascular disease in low-risk MDS patients (P = .043 and P = .036, respectively).

Study details: The data come from a retrospective analysis of 236 MDS patients aged 18 years and older who were seen and treated at a single center between 2010 and 2018.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.  

Citation: Faber MG et al. eJHaem. 2020 Sept 28. doi: 10.1002/jha2.101.

Key clinical point: Gene mutations involving ASXL1 were significantly associated with increased risk of vascular events in adults with myelodysplastic syndrome, but Trisomy 8 appeared to have a protective effect.

Major finding: Overall, the incidence of vascular disease in the study population was 27%; mutations in the ASXL1 in particular were significant predictors of vascular disease in multivariate analysis (odds ratio 4.2); however, both elevated ferritin and Trisomy 8 were significantly associated with a lower risk of vascular disease in low-risk MDS patients (P = .043 and P = .036, respectively).

Study details: The data come from a retrospective analysis of 236 MDS patients aged 18 years and older who were seen and treated at a single center between 2010 and 2018.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.  

Citation: Faber MG et al. eJHaem. 2020 Sept 28. doi: 10.1002/jha2.101.

Key clinical point: Gene mutations involving ASXL1 were significantly associated with increased risk of vascular events in adults with myelodysplastic syndrome, but Trisomy 8 appeared to have a protective effect.

Major finding: Overall, the incidence of vascular disease in the study population was 27%; mutations in the ASXL1 in particular were significant predictors of vascular disease in multivariate analysis (odds ratio 4.2); however, both elevated ferritin and Trisomy 8 were significantly associated with a lower risk of vascular disease in low-risk MDS patients (P = .043 and P = .036, respectively).

Study details: The data come from a retrospective analysis of 236 MDS patients aged 18 years and older who were seen and treated at a single center between 2010 and 2018.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.  

Citation: Faber MG et al. eJHaem. 2020 Sept 28. doi: 10.1002/jha2.101.

Key clinical point: Myelodysplastic syndrome patients who had a slower luspatercept apparent clearance (CL/F) were more likely to achieve erythroid responses, suggesting potential as an early efficacy marker.

Major finding: Luspatercept given over a dose range of 0.125 mg/kg-1.75 mg/kg yielded linear and time-invariant pharmacokinetics when given to MDS patients with anemia subcutaneously once every 3 weeks; the odds of transfusion independence at a minimum of 8 weeks increased with time-averaged exposure and plateaued at 1.0 mg/kg-1.75 mg/kg.

Study details: The data come from a review of several studies including 260 adults with anemia caused by myelodysplastic syndromes.

Disclosures: The studies in the review were funded by Bristol Myers Squibb or Acceleron. Lead author Dr. Chen and several coauthors are employees of Bristol Myers Squibb.

Citation: Chen N et al. CPT Pharmacometrics Syst Pharmacol. 2020 June 30. doi: 10.1002/psp4.12521.

Key clinical point: Myelodysplastic syndrome patients who had a slower luspatercept apparent clearance (CL/F) were more likely to achieve erythroid responses, suggesting potential as an early efficacy marker.

Major finding: Luspatercept given over a dose range of 0.125 mg/kg-1.75 mg/kg yielded linear and time-invariant pharmacokinetics when given to MDS patients with anemia subcutaneously once every 3 weeks; the odds of transfusion independence at a minimum of 8 weeks increased with time-averaged exposure and plateaued at 1.0 mg/kg-1.75 mg/kg.

Study details: The data come from a review of several studies including 260 adults with anemia caused by myelodysplastic syndromes.

Disclosures: The studies in the review were funded by Bristol Myers Squibb or Acceleron. Lead author Dr. Chen and several coauthors are employees of Bristol Myers Squibb.

Citation: Chen N et al. CPT Pharmacometrics Syst Pharmacol. 2020 June 30. doi: 10.1002/psp4.12521.

Key clinical point: Myelodysplastic syndrome patients who had a slower luspatercept apparent clearance (CL/F) were more likely to achieve erythroid responses, suggesting potential as an early efficacy marker.

Major finding: Luspatercept given over a dose range of 0.125 mg/kg-1.75 mg/kg yielded linear and time-invariant pharmacokinetics when given to MDS patients with anemia subcutaneously once every 3 weeks; the odds of transfusion independence at a minimum of 8 weeks increased with time-averaged exposure and plateaued at 1.0 mg/kg-1.75 mg/kg.

Study details: The data come from a review of several studies including 260 adults with anemia caused by myelodysplastic syndromes.

Disclosures: The studies in the review were funded by Bristol Myers Squibb or Acceleron. Lead author Dr. Chen and several coauthors are employees of Bristol Myers Squibb.

Citation: Chen N et al. CPT Pharmacometrics Syst Pharmacol. 2020 June 30. doi: 10.1002/psp4.12521.