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POEM outcomes ‘outstanding’ in achalasia with long-term follow-up
PHILADELPHIA – , Stavros N. Stavropoulos, MD, said at a meeting jointly provided by Rutgers and Global Academy for Medical Education.
“POEM represents a first-line treatment option for achalasia that has equivalent or superior efficacy to Heller [myotomy],” said Dr. Stavropoulos, MD, director of the program in advanced GI endoscopy at NYU Winthrop Hospital, Mineola, N.Y.
Although POEM is associated with more gastrointestinal reflux disease (GERD) than laparoscopic Heller myotomy, there is some evidence that the advantage of Heller in this respect may decrease over time, he told attendees.
“GERD after POEM is easily treatable with proton pump inhibitors (PPIs), with good patient satisfaction and no significant long-term GERD complications,” Dr. Stavropoulos said in a presentation on minimally invasive approaches to esophageal disorders.
NYU Winthrop Hospital was the site of the first human POEM outside of Japan, performed in 2009 by Dr. Stavropoulos, who along with colleagues recently published what he said is the largest single-operator POEM series in the Western hemisphere.
That report in Gastrointestinal Endoscopy (2018 Apr;87[4]:972-85) was based on 318 consecutive POEMs performed through October 2016. Dr. Stavropoulos and colleagues reported that over a median follow-up of 28 months they had a 95.7% clinical success rate, defined as a Eckardt score of 3 or more and no further treatment needed.
Those results suggested POEM should be a “treatment of choice” for challenging cases managed at centers who have a high level of experience with the procedure, the investigators said at the time.
Dr. Stavropoulos presented his center’s updated experience including 515 patients undergoing POEM, with a median follow-up of 37 months. About 50% of the patients were previously treated, including 73 (14% who underwent Heller myotomy).
Mean Eckardt scores were 7.7 preprocedure and 0.5 post procedure, while on timed barium swallow, emptying of 50% or greater at 5 minutes was seen in 96% of patients, and 100% emptying at 5 minutes was seen in 68%, according to data Dr. Stavropoulos presented.
Disease-free probability was 99% at 1 year and 90% at 5 years, he added.
There were no deaths, leaks, aborted procedures, or need for drains in this series, according to the investigator. Three percent of patients had a hospitalization exceeding 5 days, while 1% were readmitted because of minor adverse events related to POEM, such as dehydration, Dr. Stavropoulos reported.
In 2017, the American Gastroenterological Association published a clinical practice update “legitimizing” POEM as a first-line achalasia treatment, Dr. Stavropoulos said. That update said POEM should be performed in high-volume centers by experienced physicians.
Patients who experience GERD after POEM can be effectively treated with standard, once-daily PPI therapy, according to the expert.
“The absolute difference in GERD rates between laparoscopic Heller myotomy and POEM is 20%-25% at 1 year, but may decrease with time, and may be associated with inferior dysphagia relief in LHM patients,” Dr. Stavropoulos told attendees.
Dr. Stavropoulos disclosed that he is a consultant for Boston Scientific and ERBE.
Global Academy and this news organization are owned by the same company.
PHILADELPHIA – , Stavros N. Stavropoulos, MD, said at a meeting jointly provided by Rutgers and Global Academy for Medical Education.
“POEM represents a first-line treatment option for achalasia that has equivalent or superior efficacy to Heller [myotomy],” said Dr. Stavropoulos, MD, director of the program in advanced GI endoscopy at NYU Winthrop Hospital, Mineola, N.Y.
Although POEM is associated with more gastrointestinal reflux disease (GERD) than laparoscopic Heller myotomy, there is some evidence that the advantage of Heller in this respect may decrease over time, he told attendees.
“GERD after POEM is easily treatable with proton pump inhibitors (PPIs), with good patient satisfaction and no significant long-term GERD complications,” Dr. Stavropoulos said in a presentation on minimally invasive approaches to esophageal disorders.
NYU Winthrop Hospital was the site of the first human POEM outside of Japan, performed in 2009 by Dr. Stavropoulos, who along with colleagues recently published what he said is the largest single-operator POEM series in the Western hemisphere.
That report in Gastrointestinal Endoscopy (2018 Apr;87[4]:972-85) was based on 318 consecutive POEMs performed through October 2016. Dr. Stavropoulos and colleagues reported that over a median follow-up of 28 months they had a 95.7% clinical success rate, defined as a Eckardt score of 3 or more and no further treatment needed.
Those results suggested POEM should be a “treatment of choice” for challenging cases managed at centers who have a high level of experience with the procedure, the investigators said at the time.
Dr. Stavropoulos presented his center’s updated experience including 515 patients undergoing POEM, with a median follow-up of 37 months. About 50% of the patients were previously treated, including 73 (14% who underwent Heller myotomy).
Mean Eckardt scores were 7.7 preprocedure and 0.5 post procedure, while on timed barium swallow, emptying of 50% or greater at 5 minutes was seen in 96% of patients, and 100% emptying at 5 minutes was seen in 68%, according to data Dr. Stavropoulos presented.
Disease-free probability was 99% at 1 year and 90% at 5 years, he added.
There were no deaths, leaks, aborted procedures, or need for drains in this series, according to the investigator. Three percent of patients had a hospitalization exceeding 5 days, while 1% were readmitted because of minor adverse events related to POEM, such as dehydration, Dr. Stavropoulos reported.
In 2017, the American Gastroenterological Association published a clinical practice update “legitimizing” POEM as a first-line achalasia treatment, Dr. Stavropoulos said. That update said POEM should be performed in high-volume centers by experienced physicians.
Patients who experience GERD after POEM can be effectively treated with standard, once-daily PPI therapy, according to the expert.
“The absolute difference in GERD rates between laparoscopic Heller myotomy and POEM is 20%-25% at 1 year, but may decrease with time, and may be associated with inferior dysphagia relief in LHM patients,” Dr. Stavropoulos told attendees.
Dr. Stavropoulos disclosed that he is a consultant for Boston Scientific and ERBE.
Global Academy and this news organization are owned by the same company.
PHILADELPHIA – , Stavros N. Stavropoulos, MD, said at a meeting jointly provided by Rutgers and Global Academy for Medical Education.
“POEM represents a first-line treatment option for achalasia that has equivalent or superior efficacy to Heller [myotomy],” said Dr. Stavropoulos, MD, director of the program in advanced GI endoscopy at NYU Winthrop Hospital, Mineola, N.Y.
Although POEM is associated with more gastrointestinal reflux disease (GERD) than laparoscopic Heller myotomy, there is some evidence that the advantage of Heller in this respect may decrease over time, he told attendees.
“GERD after POEM is easily treatable with proton pump inhibitors (PPIs), with good patient satisfaction and no significant long-term GERD complications,” Dr. Stavropoulos said in a presentation on minimally invasive approaches to esophageal disorders.
NYU Winthrop Hospital was the site of the first human POEM outside of Japan, performed in 2009 by Dr. Stavropoulos, who along with colleagues recently published what he said is the largest single-operator POEM series in the Western hemisphere.
That report in Gastrointestinal Endoscopy (2018 Apr;87[4]:972-85) was based on 318 consecutive POEMs performed through October 2016. Dr. Stavropoulos and colleagues reported that over a median follow-up of 28 months they had a 95.7% clinical success rate, defined as a Eckardt score of 3 or more and no further treatment needed.
Those results suggested POEM should be a “treatment of choice” for challenging cases managed at centers who have a high level of experience with the procedure, the investigators said at the time.
Dr. Stavropoulos presented his center’s updated experience including 515 patients undergoing POEM, with a median follow-up of 37 months. About 50% of the patients were previously treated, including 73 (14% who underwent Heller myotomy).
Mean Eckardt scores were 7.7 preprocedure and 0.5 post procedure, while on timed barium swallow, emptying of 50% or greater at 5 minutes was seen in 96% of patients, and 100% emptying at 5 minutes was seen in 68%, according to data Dr. Stavropoulos presented.
Disease-free probability was 99% at 1 year and 90% at 5 years, he added.
There were no deaths, leaks, aborted procedures, or need for drains in this series, according to the investigator. Three percent of patients had a hospitalization exceeding 5 days, while 1% were readmitted because of minor adverse events related to POEM, such as dehydration, Dr. Stavropoulos reported.
In 2017, the American Gastroenterological Association published a clinical practice update “legitimizing” POEM as a first-line achalasia treatment, Dr. Stavropoulos said. That update said POEM should be performed in high-volume centers by experienced physicians.
Patients who experience GERD after POEM can be effectively treated with standard, once-daily PPI therapy, according to the expert.
“The absolute difference in GERD rates between laparoscopic Heller myotomy and POEM is 20%-25% at 1 year, but may decrease with time, and may be associated with inferior dysphagia relief in LHM patients,” Dr. Stavropoulos told attendees.
Dr. Stavropoulos disclosed that he is a consultant for Boston Scientific and ERBE.
Global Academy and this news organization are owned by the same company.
REPORTING FROM DIGESTIVE DISEASES: NEW ADVANCES
Algorithm ruled out PE, averts radiation exposure in pregnant women
A diagnostic algorithm adapted for use in pregnancy safely ruled out acute pulmonary embolism in nearly 500 women with suspected pulmonary embolism enrolled in a recent prospective study, investigators are reporting.
Using the adapted algorithm, there was only one deep-vein thrombosis (DVT) and no pulmonary embolism (PE) in follow-up among those women, according to the investigators, including senior author Menno V. Huisman, MD, PhD, of the department of thrombosis and hemostasis at Leiden (Netherlands) University Medical Center and his coauthors.
The main advantage of the algorithm is that it averted CT pulmonary angiography in nearly 40% of patients, thus sparing radiation exposure to mother and fetus in many cases, the investigators added.
“Our algorithm provides solid evidence for the safe management of suspected PE in pregnant women, with selective use of CT pulmonary angiography,” Dr. Huisman and colleagues said in their March 21 report in the New England Journal of Medicine.
In a previous clinical trial, known as the YEARS study, a specialized diagnostic algorithm had a low incidence of failure in men and women with clinically suspected PE, as shown by a venous thromboembolism (VTE) rate of just 0.61% at 3 months and by use of CT pulmonary angiography that was 14 percentage points lower than with a conventional algorithmic approach.
For the current study, Dr. Huisman and his coinvestigators took the YEARS algorithm and adapted it for use in pregnant women with suspected PE presenting at 1 of 18 centers in the Netherlands, France, and Ireland.
Their adapted algorithm was based on the three criteria investigators said were most predictive in the YEARS trial, namely, clinical signs of symptoms of DVT, hemoptysis, and PE as the most likely diagnosis. Patients also underwent D-dimer testing, and if they had clinical signs and symptoms of DVT, underwent compression utrasonography of the symptomatic leg.
Pulmonary embolism was considered ruled out in patients who met none of the three YEARS criteria and had a D-dimer under 1,000 ng/mL, or if they met one to three YEARS criteria and had a D-dimer under 500 ng/mL. Otherwise, patients underwent CT pulmonary angiography and started anticoagulant treatment if results of that test indicated PE.
The primary endpoint of the study was the cumulative 3-month incidence of symptomatic VTE among patients with PE ruled out by this algorithm.
Of 498 patients participating in the study, 477 (96%) had a negative result on the adapted YEARS algorithm at baseline, while 20 (4.0%) received a diagnosis of PE, according to results of the study. One patient was lost to follow-up.
Of the 477 patients with negative results, 1 patient (0.21%) had a diagnosis of symptomatic DVT over the 3 months of follow-up, investigators reported, adding that there were no PE diagnoses over the follow-up period.
That patient with the DVT diagnosis met none of the three YEARS criteria and had a D-dimer level of 480 ng/mL, and so did not undergo CT pulmonary angiography, investigators said.
In the worst-case scenario, the VTE incidence would have been 0.42%, assuming the one patient lost to follow-up would have had a VTE diagnosis over the 3-month follow-up period, they added.
“These data meet the proposed criteria for assessing the safety of diagnostic methods in VTE, even in the context of a low baseline prevalence of disease,” Dr. Huisman and his colleagues wrote.
Overall, CT pulmonary angiography was avoided – avoiding potential radiation exposure-related harms– in 39% of the patients, the investigators said, noting that the proportion of women avoiding the diagnostic test decreased from 65% for those evaluated in the third trimester, 46% in the second trimester, and 32% in the third.
“This decreasing specificity can be explained by the physiological rise in the D-dimer level that commonly occurs during pregnancy,” said Dr. Huisman and his coauthors.
The study was supported by unrestricted grants from Leiden University Medical Center and 17 other participating hospitals. Many authors reported financial ties to the pharmaceutical industry.
SOURCE: van der Pol LM et al. N Engl J Med. 2019;380:1139-49
A diagnostic algorithm adapted for use in pregnancy safely ruled out acute pulmonary embolism in nearly 500 women with suspected pulmonary embolism enrolled in a recent prospective study, investigators are reporting.
Using the adapted algorithm, there was only one deep-vein thrombosis (DVT) and no pulmonary embolism (PE) in follow-up among those women, according to the investigators, including senior author Menno V. Huisman, MD, PhD, of the department of thrombosis and hemostasis at Leiden (Netherlands) University Medical Center and his coauthors.
The main advantage of the algorithm is that it averted CT pulmonary angiography in nearly 40% of patients, thus sparing radiation exposure to mother and fetus in many cases, the investigators added.
“Our algorithm provides solid evidence for the safe management of suspected PE in pregnant women, with selective use of CT pulmonary angiography,” Dr. Huisman and colleagues said in their March 21 report in the New England Journal of Medicine.
In a previous clinical trial, known as the YEARS study, a specialized diagnostic algorithm had a low incidence of failure in men and women with clinically suspected PE, as shown by a venous thromboembolism (VTE) rate of just 0.61% at 3 months and by use of CT pulmonary angiography that was 14 percentage points lower than with a conventional algorithmic approach.
For the current study, Dr. Huisman and his coinvestigators took the YEARS algorithm and adapted it for use in pregnant women with suspected PE presenting at 1 of 18 centers in the Netherlands, France, and Ireland.
Their adapted algorithm was based on the three criteria investigators said were most predictive in the YEARS trial, namely, clinical signs of symptoms of DVT, hemoptysis, and PE as the most likely diagnosis. Patients also underwent D-dimer testing, and if they had clinical signs and symptoms of DVT, underwent compression utrasonography of the symptomatic leg.
Pulmonary embolism was considered ruled out in patients who met none of the three YEARS criteria and had a D-dimer under 1,000 ng/mL, or if they met one to three YEARS criteria and had a D-dimer under 500 ng/mL. Otherwise, patients underwent CT pulmonary angiography and started anticoagulant treatment if results of that test indicated PE.
The primary endpoint of the study was the cumulative 3-month incidence of symptomatic VTE among patients with PE ruled out by this algorithm.
Of 498 patients participating in the study, 477 (96%) had a negative result on the adapted YEARS algorithm at baseline, while 20 (4.0%) received a diagnosis of PE, according to results of the study. One patient was lost to follow-up.
Of the 477 patients with negative results, 1 patient (0.21%) had a diagnosis of symptomatic DVT over the 3 months of follow-up, investigators reported, adding that there were no PE diagnoses over the follow-up period.
That patient with the DVT diagnosis met none of the three YEARS criteria and had a D-dimer level of 480 ng/mL, and so did not undergo CT pulmonary angiography, investigators said.
In the worst-case scenario, the VTE incidence would have been 0.42%, assuming the one patient lost to follow-up would have had a VTE diagnosis over the 3-month follow-up period, they added.
“These data meet the proposed criteria for assessing the safety of diagnostic methods in VTE, even in the context of a low baseline prevalence of disease,” Dr. Huisman and his colleagues wrote.
Overall, CT pulmonary angiography was avoided – avoiding potential radiation exposure-related harms– in 39% of the patients, the investigators said, noting that the proportion of women avoiding the diagnostic test decreased from 65% for those evaluated in the third trimester, 46% in the second trimester, and 32% in the third.
“This decreasing specificity can be explained by the physiological rise in the D-dimer level that commonly occurs during pregnancy,” said Dr. Huisman and his coauthors.
The study was supported by unrestricted grants from Leiden University Medical Center and 17 other participating hospitals. Many authors reported financial ties to the pharmaceutical industry.
SOURCE: van der Pol LM et al. N Engl J Med. 2019;380:1139-49
A diagnostic algorithm adapted for use in pregnancy safely ruled out acute pulmonary embolism in nearly 500 women with suspected pulmonary embolism enrolled in a recent prospective study, investigators are reporting.
Using the adapted algorithm, there was only one deep-vein thrombosis (DVT) and no pulmonary embolism (PE) in follow-up among those women, according to the investigators, including senior author Menno V. Huisman, MD, PhD, of the department of thrombosis and hemostasis at Leiden (Netherlands) University Medical Center and his coauthors.
The main advantage of the algorithm is that it averted CT pulmonary angiography in nearly 40% of patients, thus sparing radiation exposure to mother and fetus in many cases, the investigators added.
“Our algorithm provides solid evidence for the safe management of suspected PE in pregnant women, with selective use of CT pulmonary angiography,” Dr. Huisman and colleagues said in their March 21 report in the New England Journal of Medicine.
In a previous clinical trial, known as the YEARS study, a specialized diagnostic algorithm had a low incidence of failure in men and women with clinically suspected PE, as shown by a venous thromboembolism (VTE) rate of just 0.61% at 3 months and by use of CT pulmonary angiography that was 14 percentage points lower than with a conventional algorithmic approach.
For the current study, Dr. Huisman and his coinvestigators took the YEARS algorithm and adapted it for use in pregnant women with suspected PE presenting at 1 of 18 centers in the Netherlands, France, and Ireland.
Their adapted algorithm was based on the three criteria investigators said were most predictive in the YEARS trial, namely, clinical signs of symptoms of DVT, hemoptysis, and PE as the most likely diagnosis. Patients also underwent D-dimer testing, and if they had clinical signs and symptoms of DVT, underwent compression utrasonography of the symptomatic leg.
Pulmonary embolism was considered ruled out in patients who met none of the three YEARS criteria and had a D-dimer under 1,000 ng/mL, or if they met one to three YEARS criteria and had a D-dimer under 500 ng/mL. Otherwise, patients underwent CT pulmonary angiography and started anticoagulant treatment if results of that test indicated PE.
The primary endpoint of the study was the cumulative 3-month incidence of symptomatic VTE among patients with PE ruled out by this algorithm.
Of 498 patients participating in the study, 477 (96%) had a negative result on the adapted YEARS algorithm at baseline, while 20 (4.0%) received a diagnosis of PE, according to results of the study. One patient was lost to follow-up.
Of the 477 patients with negative results, 1 patient (0.21%) had a diagnosis of symptomatic DVT over the 3 months of follow-up, investigators reported, adding that there were no PE diagnoses over the follow-up period.
That patient with the DVT diagnosis met none of the three YEARS criteria and had a D-dimer level of 480 ng/mL, and so did not undergo CT pulmonary angiography, investigators said.
In the worst-case scenario, the VTE incidence would have been 0.42%, assuming the one patient lost to follow-up would have had a VTE diagnosis over the 3-month follow-up period, they added.
“These data meet the proposed criteria for assessing the safety of diagnostic methods in VTE, even in the context of a low baseline prevalence of disease,” Dr. Huisman and his colleagues wrote.
Overall, CT pulmonary angiography was avoided – avoiding potential radiation exposure-related harms– in 39% of the patients, the investigators said, noting that the proportion of women avoiding the diagnostic test decreased from 65% for those evaluated in the third trimester, 46% in the second trimester, and 32% in the third.
“This decreasing specificity can be explained by the physiological rise in the D-dimer level that commonly occurs during pregnancy,” said Dr. Huisman and his coauthors.
The study was supported by unrestricted grants from Leiden University Medical Center and 17 other participating hospitals. Many authors reported financial ties to the pharmaceutical industry.
SOURCE: van der Pol LM et al. N Engl J Med. 2019;380:1139-49
FROM The New England Journal of Medicine
Home oxygen therapy for children: New guidelines combine limited evidence, expert experience
Based on the very limited evidence available, an expert panel convened by the .
The guideline authors not only addressed specific indications for chronic lung and pulmonary vascular diseases, but also defined hypoxemia in children – noting that Medicare and Medicaid coverage determinations for home oxygen therapy in children are based on decades-old studies that lacked pediatric patients – and offer expert advice on how to wean and discontinue oxygen, when warranted.
The disease-specific recommendations on whether or not to prescribe home oxygen therapy are characterized either as strong, meaning that it’s the right course of action for at least 95% of patients; or conditional, meaning it might not be right for a “sizable minority” of patients, authors explained in the guideline.
Home oxygen therapy gets a strong recommendation, for example, in patients with cystic fibrosis complicated by severe chronic hypoxemia, but gets a conditional recommendation for sickle cell disease with severe chronic hypoxemia, according to the guideline, published in the American Journal of Respiratory and Critical Care Medicine.
Regardless of strong or conditional, the recommendations were largely based on “very low-quality evidence,” according to ad hoc subcommittee of the ATS Assembly on Pediatrics, cochaired by Don Hayes Jr., MD, of Nationwide Children’s Hospital, Columbus, Ohio, and Robin R. Deterding, MD, of Children’s Hospital Colorado, Denver.
“Despite widespread use of home oxygen therapy for various lung and pulmonary vascular diseases, there is a striking paucity of data regarding its implementation, efficacy, monitoring, and discontinuation,” Dr. Hayes, Dr. Deterding, and 20 additional committee members wrote in their report.
Accordingly, the panel sought to add expert opinion and experience to the limited evidence, in the hope that it would aid clinicians in the management of complex pediatric patients, they said.
One new tool they provide, toward that end, is a definition of hypoxemia in children based on oxygen saturation as quantified by pulse oximetry (SpO2).
Based on a review of 31 selected studies measuring oxygenation in healthy children, the expert panel defined hypoxemia (at or near sea level) as SpO2 of 90% or lower for 5% of the recording time in children under 1 year old, and an SpO2 of 93% or lower in older children; or alternately, as three independent measurements of SpO2 less than or equal to 90% in the younger children and 93% in the older children.
By contrast, an SpO2 of less than 88% is one of the indications for funding home oxygen therapy as determined by the Centers for Medicare & Medicaid Services for both pediatric and adult patients, according to the committee.
The CMS indications derived from “seminal studies” showing that continuous oxygen therapy reduced mortality in adults with chronic obstructive pulmonary disease, they said in the guideline document.
“Despite the lack of pediatric patients in these historic studies performed over 35 years ago, the CMS coverage determination for [home oxygen therapy] is the same for pediatric patients of all ages compared with adult patients,” they wrote in the report.
The committee unanimously agreed that 2 weeks of low SpO2 was “sufficient evidence” to indicate chronic hypoxemia, their report says.
Dr. Hayes reported no relationships with relevant commercial interests, while Dr. Deterding provided disclosures related to Boehringer Ingelheim, Novartis, and Elsevier Publishing, among others. Fellow committee members provided disclosures related to Shire Pharmaceuticals, United Therapeutics, and others as listed in the clinical practice guideline document.
SOURCE: Hayes D Jr. et al. J Respir Crit Care Med. 2019 Feb 1;199(3):e5-e23. doi: 10.1164/rccm.201812-2276ST.
It is unfortunate that over the course of a decade, the evidence base supporting home oxygen therapy in children has not substantially changed, according to Ian Balfour-Lynn, MD, a member of the American Thoracic Society (ATS) committee that developed the clinical practice guideline.
The ATS clinical practice guideline on home oxygen therapy for children echoes conclusions reached in a 2009 guideline published by the British Thoracic Society (BTS), he wrote in The Lancet Respiratory Medicine.
Dr. Balfour-Lynn, who chaired the BTS guideline committee, said new research is sorely needed, particularly in the prevention of preterm births, which he said constitute the commonest cause of home oxygen need among children, according to the Lancet report.
In addition, a large prospective trial is needed to evaluate strategies for weaning or discontinuing oxygen, he said, noting that the ATS recommendations on weaning were almost entirely based on the expert panel’s combined clinical experience.
Dr. Balfour-Lynn is a consultant in pediatric respiratory medicine at Royal Brompton Hospital, London. This summary of his opinions is based on his comments in a report that appeared March 8 in The Lancet Respiratory Medicine . He reported no relationships with commercial interests relevant to his work on the ATS clinical practice guideline.
It is unfortunate that over the course of a decade, the evidence base supporting home oxygen therapy in children has not substantially changed, according to Ian Balfour-Lynn, MD, a member of the American Thoracic Society (ATS) committee that developed the clinical practice guideline.
The ATS clinical practice guideline on home oxygen therapy for children echoes conclusions reached in a 2009 guideline published by the British Thoracic Society (BTS), he wrote in The Lancet Respiratory Medicine.
Dr. Balfour-Lynn, who chaired the BTS guideline committee, said new research is sorely needed, particularly in the prevention of preterm births, which he said constitute the commonest cause of home oxygen need among children, according to the Lancet report.
In addition, a large prospective trial is needed to evaluate strategies for weaning or discontinuing oxygen, he said, noting that the ATS recommendations on weaning were almost entirely based on the expert panel’s combined clinical experience.
Dr. Balfour-Lynn is a consultant in pediatric respiratory medicine at Royal Brompton Hospital, London. This summary of his opinions is based on his comments in a report that appeared March 8 in The Lancet Respiratory Medicine . He reported no relationships with commercial interests relevant to his work on the ATS clinical practice guideline.
It is unfortunate that over the course of a decade, the evidence base supporting home oxygen therapy in children has not substantially changed, according to Ian Balfour-Lynn, MD, a member of the American Thoracic Society (ATS) committee that developed the clinical practice guideline.
The ATS clinical practice guideline on home oxygen therapy for children echoes conclusions reached in a 2009 guideline published by the British Thoracic Society (BTS), he wrote in The Lancet Respiratory Medicine.
Dr. Balfour-Lynn, who chaired the BTS guideline committee, said new research is sorely needed, particularly in the prevention of preterm births, which he said constitute the commonest cause of home oxygen need among children, according to the Lancet report.
In addition, a large prospective trial is needed to evaluate strategies for weaning or discontinuing oxygen, he said, noting that the ATS recommendations on weaning were almost entirely based on the expert panel’s combined clinical experience.
Dr. Balfour-Lynn is a consultant in pediatric respiratory medicine at Royal Brompton Hospital, London. This summary of his opinions is based on his comments in a report that appeared March 8 in The Lancet Respiratory Medicine . He reported no relationships with commercial interests relevant to his work on the ATS clinical practice guideline.
Based on the very limited evidence available, an expert panel convened by the .
The guideline authors not only addressed specific indications for chronic lung and pulmonary vascular diseases, but also defined hypoxemia in children – noting that Medicare and Medicaid coverage determinations for home oxygen therapy in children are based on decades-old studies that lacked pediatric patients – and offer expert advice on how to wean and discontinue oxygen, when warranted.
The disease-specific recommendations on whether or not to prescribe home oxygen therapy are characterized either as strong, meaning that it’s the right course of action for at least 95% of patients; or conditional, meaning it might not be right for a “sizable minority” of patients, authors explained in the guideline.
Home oxygen therapy gets a strong recommendation, for example, in patients with cystic fibrosis complicated by severe chronic hypoxemia, but gets a conditional recommendation for sickle cell disease with severe chronic hypoxemia, according to the guideline, published in the American Journal of Respiratory and Critical Care Medicine.
Regardless of strong or conditional, the recommendations were largely based on “very low-quality evidence,” according to ad hoc subcommittee of the ATS Assembly on Pediatrics, cochaired by Don Hayes Jr., MD, of Nationwide Children’s Hospital, Columbus, Ohio, and Robin R. Deterding, MD, of Children’s Hospital Colorado, Denver.
“Despite widespread use of home oxygen therapy for various lung and pulmonary vascular diseases, there is a striking paucity of data regarding its implementation, efficacy, monitoring, and discontinuation,” Dr. Hayes, Dr. Deterding, and 20 additional committee members wrote in their report.
Accordingly, the panel sought to add expert opinion and experience to the limited evidence, in the hope that it would aid clinicians in the management of complex pediatric patients, they said.
One new tool they provide, toward that end, is a definition of hypoxemia in children based on oxygen saturation as quantified by pulse oximetry (SpO2).
Based on a review of 31 selected studies measuring oxygenation in healthy children, the expert panel defined hypoxemia (at or near sea level) as SpO2 of 90% or lower for 5% of the recording time in children under 1 year old, and an SpO2 of 93% or lower in older children; or alternately, as three independent measurements of SpO2 less than or equal to 90% in the younger children and 93% in the older children.
By contrast, an SpO2 of less than 88% is one of the indications for funding home oxygen therapy as determined by the Centers for Medicare & Medicaid Services for both pediatric and adult patients, according to the committee.
The CMS indications derived from “seminal studies” showing that continuous oxygen therapy reduced mortality in adults with chronic obstructive pulmonary disease, they said in the guideline document.
“Despite the lack of pediatric patients in these historic studies performed over 35 years ago, the CMS coverage determination for [home oxygen therapy] is the same for pediatric patients of all ages compared with adult patients,” they wrote in the report.
The committee unanimously agreed that 2 weeks of low SpO2 was “sufficient evidence” to indicate chronic hypoxemia, their report says.
Dr. Hayes reported no relationships with relevant commercial interests, while Dr. Deterding provided disclosures related to Boehringer Ingelheim, Novartis, and Elsevier Publishing, among others. Fellow committee members provided disclosures related to Shire Pharmaceuticals, United Therapeutics, and others as listed in the clinical practice guideline document.
SOURCE: Hayes D Jr. et al. J Respir Crit Care Med. 2019 Feb 1;199(3):e5-e23. doi: 10.1164/rccm.201812-2276ST.
Based on the very limited evidence available, an expert panel convened by the .
The guideline authors not only addressed specific indications for chronic lung and pulmonary vascular diseases, but also defined hypoxemia in children – noting that Medicare and Medicaid coverage determinations for home oxygen therapy in children are based on decades-old studies that lacked pediatric patients – and offer expert advice on how to wean and discontinue oxygen, when warranted.
The disease-specific recommendations on whether or not to prescribe home oxygen therapy are characterized either as strong, meaning that it’s the right course of action for at least 95% of patients; or conditional, meaning it might not be right for a “sizable minority” of patients, authors explained in the guideline.
Home oxygen therapy gets a strong recommendation, for example, in patients with cystic fibrosis complicated by severe chronic hypoxemia, but gets a conditional recommendation for sickle cell disease with severe chronic hypoxemia, according to the guideline, published in the American Journal of Respiratory and Critical Care Medicine.
Regardless of strong or conditional, the recommendations were largely based on “very low-quality evidence,” according to ad hoc subcommittee of the ATS Assembly on Pediatrics, cochaired by Don Hayes Jr., MD, of Nationwide Children’s Hospital, Columbus, Ohio, and Robin R. Deterding, MD, of Children’s Hospital Colorado, Denver.
“Despite widespread use of home oxygen therapy for various lung and pulmonary vascular diseases, there is a striking paucity of data regarding its implementation, efficacy, monitoring, and discontinuation,” Dr. Hayes, Dr. Deterding, and 20 additional committee members wrote in their report.
Accordingly, the panel sought to add expert opinion and experience to the limited evidence, in the hope that it would aid clinicians in the management of complex pediatric patients, they said.
One new tool they provide, toward that end, is a definition of hypoxemia in children based on oxygen saturation as quantified by pulse oximetry (SpO2).
Based on a review of 31 selected studies measuring oxygenation in healthy children, the expert panel defined hypoxemia (at or near sea level) as SpO2 of 90% or lower for 5% of the recording time in children under 1 year old, and an SpO2 of 93% or lower in older children; or alternately, as three independent measurements of SpO2 less than or equal to 90% in the younger children and 93% in the older children.
By contrast, an SpO2 of less than 88% is one of the indications for funding home oxygen therapy as determined by the Centers for Medicare & Medicaid Services for both pediatric and adult patients, according to the committee.
The CMS indications derived from “seminal studies” showing that continuous oxygen therapy reduced mortality in adults with chronic obstructive pulmonary disease, they said in the guideline document.
“Despite the lack of pediatric patients in these historic studies performed over 35 years ago, the CMS coverage determination for [home oxygen therapy] is the same for pediatric patients of all ages compared with adult patients,” they wrote in the report.
The committee unanimously agreed that 2 weeks of low SpO2 was “sufficient evidence” to indicate chronic hypoxemia, their report says.
Dr. Hayes reported no relationships with relevant commercial interests, while Dr. Deterding provided disclosures related to Boehringer Ingelheim, Novartis, and Elsevier Publishing, among others. Fellow committee members provided disclosures related to Shire Pharmaceuticals, United Therapeutics, and others as listed in the clinical practice guideline document.
SOURCE: Hayes D Jr. et al. J Respir Crit Care Med. 2019 Feb 1;199(3):e5-e23. doi: 10.1164/rccm.201812-2276ST.
FROM THE AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
PPI-fracture link can’t be ruled out
PHILADELPHIA – While a potential effect can’t be ruled out, the evidence to date is inconsistent in terms of whether proton pump inhibitors increase risk of osteoporotic fractures, an expert said at the Digestive Diseases: New Advances conference jointly provided by Rutgers and Global Academy for Medical Education.
“These associations are possible,” said David C. Metz, MD, professor of medicine in the division of gastroenterology at the University of Pennsylvania, Philadelphia.
However, Dr. Metz cautioned attendees to “be cognizant of the limitations of epidemiological data,” and highlighted a recent randomized, double-blind trial he recently published with colleagues showing a lack of proton pump inhibitors (PPI) effect on bone homeostasis in healthy, postmenopausal women.
Taking all the evidence into consideration, Dr. Metz recommended judicious use of PPIs: “Don’t deny therapy because of concerns about long-term side effects. If the patient deserves the drug, they work. Use the lowest effective long-term maintenance dose, depending on the indication.”
Dr. Metz was senior author on a frequently cited 2006 report in JAMA linking long-term PPI therapy to increased hip fracture risk, particularly when given at high doses. That study “opened up a cottage industry” of researchers examining positive or negative associations with PPI therapy, he said.
In a 2016 meta-analysis including 18 studies, investigators reported in Osteoporosis International that PPIs “modestly increased” risk of hip fracture (relative risk, 1.26; 95% confidence interval, 1.16-1.36), along with similar risk increases for spine or any-site fracture. However, many of the studies incorporated into that analysis did not conclusively associate PPIs with fractures, according to Dr. Metz.
Moreover, there had been no randomized, prospective, double-blind trials on the subject published until this month, according to Dr. Metz, when he and his coauthors reported in Gastroenterology that dexlansoprazole and esomeprazole did not affect bone homeostasis in healthy, postmenopausal women. The randomized, 26-week study, mandated by the Food and Drug Administration to evaluate long-term PPI risks, was “essentially a negative study,” Dr. Metz said in his presentation.
“I think it gives us comfort in knowing to use the drug appropriately when indicated,” he said.
In the randomized study, there were no significant differences between the PPI and placebo groups in bone mineral density, parathyroid hormone levels, serum or urine levels of minerals, or calcium absorption. There were significant increases in markers of bone turnover in women receiving PPIs versus women receiving placebo, but the levels remained within the normal limits, according to the investigators.
Nevertheless, he said that clinicians do need to be mindful of a potential risk of fracture associated with PPIs, even if studies to date are inconclusive. “I don’t think that PPIs really have a biological explanation yet at this point as to why they may make your parents a little bit more fracturable, if you happen to be a postmenopausal female who’s at risk for that.”
Dr. Metz reported receiving grant/research support from AAA, Ipsen, Lexicon, and Wren Laboratories, consulting for Takeda, and serving as a board member for the North American Neuroendocrine Tumor Society. The study was funded by Takeda, which was responsible for and sponsored the study design, data collection, data interpretation, and writing of the manuscript appearing in Gastroenterology.
This news organization and Global Academy for Medical Education are owned by the same parent company.
PHILADELPHIA – While a potential effect can’t be ruled out, the evidence to date is inconsistent in terms of whether proton pump inhibitors increase risk of osteoporotic fractures, an expert said at the Digestive Diseases: New Advances conference jointly provided by Rutgers and Global Academy for Medical Education.
“These associations are possible,” said David C. Metz, MD, professor of medicine in the division of gastroenterology at the University of Pennsylvania, Philadelphia.
However, Dr. Metz cautioned attendees to “be cognizant of the limitations of epidemiological data,” and highlighted a recent randomized, double-blind trial he recently published with colleagues showing a lack of proton pump inhibitors (PPI) effect on bone homeostasis in healthy, postmenopausal women.
Taking all the evidence into consideration, Dr. Metz recommended judicious use of PPIs: “Don’t deny therapy because of concerns about long-term side effects. If the patient deserves the drug, they work. Use the lowest effective long-term maintenance dose, depending on the indication.”
Dr. Metz was senior author on a frequently cited 2006 report in JAMA linking long-term PPI therapy to increased hip fracture risk, particularly when given at high doses. That study “opened up a cottage industry” of researchers examining positive or negative associations with PPI therapy, he said.
In a 2016 meta-analysis including 18 studies, investigators reported in Osteoporosis International that PPIs “modestly increased” risk of hip fracture (relative risk, 1.26; 95% confidence interval, 1.16-1.36), along with similar risk increases for spine or any-site fracture. However, many of the studies incorporated into that analysis did not conclusively associate PPIs with fractures, according to Dr. Metz.
Moreover, there had been no randomized, prospective, double-blind trials on the subject published until this month, according to Dr. Metz, when he and his coauthors reported in Gastroenterology that dexlansoprazole and esomeprazole did not affect bone homeostasis in healthy, postmenopausal women. The randomized, 26-week study, mandated by the Food and Drug Administration to evaluate long-term PPI risks, was “essentially a negative study,” Dr. Metz said in his presentation.
“I think it gives us comfort in knowing to use the drug appropriately when indicated,” he said.
In the randomized study, there were no significant differences between the PPI and placebo groups in bone mineral density, parathyroid hormone levels, serum or urine levels of minerals, or calcium absorption. There were significant increases in markers of bone turnover in women receiving PPIs versus women receiving placebo, but the levels remained within the normal limits, according to the investigators.
Nevertheless, he said that clinicians do need to be mindful of a potential risk of fracture associated with PPIs, even if studies to date are inconclusive. “I don’t think that PPIs really have a biological explanation yet at this point as to why they may make your parents a little bit more fracturable, if you happen to be a postmenopausal female who’s at risk for that.”
Dr. Metz reported receiving grant/research support from AAA, Ipsen, Lexicon, and Wren Laboratories, consulting for Takeda, and serving as a board member for the North American Neuroendocrine Tumor Society. The study was funded by Takeda, which was responsible for and sponsored the study design, data collection, data interpretation, and writing of the manuscript appearing in Gastroenterology.
This news organization and Global Academy for Medical Education are owned by the same parent company.
PHILADELPHIA – While a potential effect can’t be ruled out, the evidence to date is inconsistent in terms of whether proton pump inhibitors increase risk of osteoporotic fractures, an expert said at the Digestive Diseases: New Advances conference jointly provided by Rutgers and Global Academy for Medical Education.
“These associations are possible,” said David C. Metz, MD, professor of medicine in the division of gastroenterology at the University of Pennsylvania, Philadelphia.
However, Dr. Metz cautioned attendees to “be cognizant of the limitations of epidemiological data,” and highlighted a recent randomized, double-blind trial he recently published with colleagues showing a lack of proton pump inhibitors (PPI) effect on bone homeostasis in healthy, postmenopausal women.
Taking all the evidence into consideration, Dr. Metz recommended judicious use of PPIs: “Don’t deny therapy because of concerns about long-term side effects. If the patient deserves the drug, they work. Use the lowest effective long-term maintenance dose, depending on the indication.”
Dr. Metz was senior author on a frequently cited 2006 report in JAMA linking long-term PPI therapy to increased hip fracture risk, particularly when given at high doses. That study “opened up a cottage industry” of researchers examining positive or negative associations with PPI therapy, he said.
In a 2016 meta-analysis including 18 studies, investigators reported in Osteoporosis International that PPIs “modestly increased” risk of hip fracture (relative risk, 1.26; 95% confidence interval, 1.16-1.36), along with similar risk increases for spine or any-site fracture. However, many of the studies incorporated into that analysis did not conclusively associate PPIs with fractures, according to Dr. Metz.
Moreover, there had been no randomized, prospective, double-blind trials on the subject published until this month, according to Dr. Metz, when he and his coauthors reported in Gastroenterology that dexlansoprazole and esomeprazole did not affect bone homeostasis in healthy, postmenopausal women. The randomized, 26-week study, mandated by the Food and Drug Administration to evaluate long-term PPI risks, was “essentially a negative study,” Dr. Metz said in his presentation.
“I think it gives us comfort in knowing to use the drug appropriately when indicated,” he said.
In the randomized study, there were no significant differences between the PPI and placebo groups in bone mineral density, parathyroid hormone levels, serum or urine levels of minerals, or calcium absorption. There were significant increases in markers of bone turnover in women receiving PPIs versus women receiving placebo, but the levels remained within the normal limits, according to the investigators.
Nevertheless, he said that clinicians do need to be mindful of a potential risk of fracture associated with PPIs, even if studies to date are inconclusive. “I don’t think that PPIs really have a biological explanation yet at this point as to why they may make your parents a little bit more fracturable, if you happen to be a postmenopausal female who’s at risk for that.”
Dr. Metz reported receiving grant/research support from AAA, Ipsen, Lexicon, and Wren Laboratories, consulting for Takeda, and serving as a board member for the North American Neuroendocrine Tumor Society. The study was funded by Takeda, which was responsible for and sponsored the study design, data collection, data interpretation, and writing of the manuscript appearing in Gastroenterology.
This news organization and Global Academy for Medical Education are owned by the same parent company.
EXPERT ANALYSIS FROM DIGESTIVE DISEASES: NEW ADVANCES
Will inpatient albumin help in decompensated cirrhosis?
PHILADELPHIA – , according to Vijay Shah, MD, chair of the division of gastroenterology and hepatology at Mayo Clinic, Rochester, Minn.
“These are interesting studies, but I don’t think we’re ready yet to use this broadly,” Dr. Shah said at the meeting jointly provided by Rutgers and Global Academy for Medical Education.
Current guidelines do describe the use of albumin for large-volume paracentesis and other specific inpatient situations; however, extrapolating its long-term use has been explored in two major studies that recently came out with contradictory findings.
In the ANSWER trial, as reported in the Lancet, investigators at 33 centers randomized patients with cirrhosis and uncomplicated ascites to either standard medical treatment with or without human albumin, at 40 g twice weekly for 2 weeks, followed by 40 g weekly for up to 18 months.
Those investigators found that long-term albumin prolonged overall survival, with a 38% reduction in the mortality hazard ratio, with similar rates of serious, nonliver adverse events, leading them to conclude that this intervention may act as a disease-modifying treatment in decompensated cirrhosis patients.
By contrast, however, a recent randomized, placebo-controlled trial reported in the Journal of Hepatology showed that albumin plus midodrine, an alpha-adrenergic vasoconstrictor, did not improve survival among patients with decompensated cirrhosis on the liver transplant waiting list, at least at the doses administered (midodrine 15-30 mg/day and albumin 40 g every 15 days for a year).
While this particular combination of albumin plus midodrine did decrease renin and aldosterone levels, the intervention did not prevent complications or improve survival, investigators said at the time. Complication rates were 37% and 43% for treatment and placebo, respectively (P = .402), with low rates of death in both groups and no significant difference in mortality at 1 year (P = .527).
Dr. Shah said the discrepant results may be attributable to specific differences in study design or enrollment.
“It’s just hand waving, but it may be related to the dose of albumin, or may be related to the types of patients – the second study was in patients who are waiting for liver transplantation,” he told attendees. “But I don’t think that there’s currently enough evidence to use albumin in your patients in the outpatient setting.”
There is a third study, recently published in the American Journal of Gastroenterology, looking at data for a large end-stage liver disease cohort with hyponatremia. Investigators observed a higher rate of hyponatremia resolution and improved 30-day survival in those who had received albumin (total mean amount, 225 g) versus those who had not.
Considering all of this evidence taken together, Dr. Shah said he would not favor using outpatient albumin at this point – though he advised attendees to watch for a currently recruiting phase 3 randomized study, known as PRECIOSA, which is evaluating long-term administration of human albumin 20% injectable solution, dosed by body weight, in patients with decompensated cirrhosis and ascites.
Dr. Shah indicated that he is a consultant for Afimmune, Durect Corporation, Enterome, GRI Bio, Merck Research Laboratories, Novartis Pharma, and Vital Therapeutics. Global Academy and this news organization are owned by the same company.
PHILADELPHIA – , according to Vijay Shah, MD, chair of the division of gastroenterology and hepatology at Mayo Clinic, Rochester, Minn.
“These are interesting studies, but I don’t think we’re ready yet to use this broadly,” Dr. Shah said at the meeting jointly provided by Rutgers and Global Academy for Medical Education.
Current guidelines do describe the use of albumin for large-volume paracentesis and other specific inpatient situations; however, extrapolating its long-term use has been explored in two major studies that recently came out with contradictory findings.
In the ANSWER trial, as reported in the Lancet, investigators at 33 centers randomized patients with cirrhosis and uncomplicated ascites to either standard medical treatment with or without human albumin, at 40 g twice weekly for 2 weeks, followed by 40 g weekly for up to 18 months.
Those investigators found that long-term albumin prolonged overall survival, with a 38% reduction in the mortality hazard ratio, with similar rates of serious, nonliver adverse events, leading them to conclude that this intervention may act as a disease-modifying treatment in decompensated cirrhosis patients.
By contrast, however, a recent randomized, placebo-controlled trial reported in the Journal of Hepatology showed that albumin plus midodrine, an alpha-adrenergic vasoconstrictor, did not improve survival among patients with decompensated cirrhosis on the liver transplant waiting list, at least at the doses administered (midodrine 15-30 mg/day and albumin 40 g every 15 days for a year).
While this particular combination of albumin plus midodrine did decrease renin and aldosterone levels, the intervention did not prevent complications or improve survival, investigators said at the time. Complication rates were 37% and 43% for treatment and placebo, respectively (P = .402), with low rates of death in both groups and no significant difference in mortality at 1 year (P = .527).
Dr. Shah said the discrepant results may be attributable to specific differences in study design or enrollment.
“It’s just hand waving, but it may be related to the dose of albumin, or may be related to the types of patients – the second study was in patients who are waiting for liver transplantation,” he told attendees. “But I don’t think that there’s currently enough evidence to use albumin in your patients in the outpatient setting.”
There is a third study, recently published in the American Journal of Gastroenterology, looking at data for a large end-stage liver disease cohort with hyponatremia. Investigators observed a higher rate of hyponatremia resolution and improved 30-day survival in those who had received albumin (total mean amount, 225 g) versus those who had not.
Considering all of this evidence taken together, Dr. Shah said he would not favor using outpatient albumin at this point – though he advised attendees to watch for a currently recruiting phase 3 randomized study, known as PRECIOSA, which is evaluating long-term administration of human albumin 20% injectable solution, dosed by body weight, in patients with decompensated cirrhosis and ascites.
Dr. Shah indicated that he is a consultant for Afimmune, Durect Corporation, Enterome, GRI Bio, Merck Research Laboratories, Novartis Pharma, and Vital Therapeutics. Global Academy and this news organization are owned by the same company.
PHILADELPHIA – , according to Vijay Shah, MD, chair of the division of gastroenterology and hepatology at Mayo Clinic, Rochester, Minn.
“These are interesting studies, but I don’t think we’re ready yet to use this broadly,” Dr. Shah said at the meeting jointly provided by Rutgers and Global Academy for Medical Education.
Current guidelines do describe the use of albumin for large-volume paracentesis and other specific inpatient situations; however, extrapolating its long-term use has been explored in two major studies that recently came out with contradictory findings.
In the ANSWER trial, as reported in the Lancet, investigators at 33 centers randomized patients with cirrhosis and uncomplicated ascites to either standard medical treatment with or without human albumin, at 40 g twice weekly for 2 weeks, followed by 40 g weekly for up to 18 months.
Those investigators found that long-term albumin prolonged overall survival, with a 38% reduction in the mortality hazard ratio, with similar rates of serious, nonliver adverse events, leading them to conclude that this intervention may act as a disease-modifying treatment in decompensated cirrhosis patients.
By contrast, however, a recent randomized, placebo-controlled trial reported in the Journal of Hepatology showed that albumin plus midodrine, an alpha-adrenergic vasoconstrictor, did not improve survival among patients with decompensated cirrhosis on the liver transplant waiting list, at least at the doses administered (midodrine 15-30 mg/day and albumin 40 g every 15 days for a year).
While this particular combination of albumin plus midodrine did decrease renin and aldosterone levels, the intervention did not prevent complications or improve survival, investigators said at the time. Complication rates were 37% and 43% for treatment and placebo, respectively (P = .402), with low rates of death in both groups and no significant difference in mortality at 1 year (P = .527).
Dr. Shah said the discrepant results may be attributable to specific differences in study design or enrollment.
“It’s just hand waving, but it may be related to the dose of albumin, or may be related to the types of patients – the second study was in patients who are waiting for liver transplantation,” he told attendees. “But I don’t think that there’s currently enough evidence to use albumin in your patients in the outpatient setting.”
There is a third study, recently published in the American Journal of Gastroenterology, looking at data for a large end-stage liver disease cohort with hyponatremia. Investigators observed a higher rate of hyponatremia resolution and improved 30-day survival in those who had received albumin (total mean amount, 225 g) versus those who had not.
Considering all of this evidence taken together, Dr. Shah said he would not favor using outpatient albumin at this point – though he advised attendees to watch for a currently recruiting phase 3 randomized study, known as PRECIOSA, which is evaluating long-term administration of human albumin 20% injectable solution, dosed by body weight, in patients with decompensated cirrhosis and ascites.
Dr. Shah indicated that he is a consultant for Afimmune, Durect Corporation, Enterome, GRI Bio, Merck Research Laboratories, Novartis Pharma, and Vital Therapeutics. Global Academy and this news organization are owned by the same company.
REPORTING FROM DIGESTIVE DISEASES: NEW ADVANCES
Long-term metformin offsets diabetes in patients with higher glucose/HbA1c, history of gestational diabetes
Metformin is especially effective in diabetes prevention among persons with higher baseline fasting glucose, higher hemoglobin A1c (HbA1c), or a history of gestational diabetes, based on 15-year follow-up results from the Diabetes Prevention Program and the Diabetes Prevention Program Outcomes Study.
Beyond those subgroups, metformin remained effective regardless of how diabetes was diagnosed, with a risk reduction of up to 36%, according to a report published in Diabetes Care.
“These results should help to prioritize those groups at high risk of developing diabetes who will benefit most from being treated with metformin,” said the report’s writing committee, chaired by David M. Nathan, MD, professor of medicine at Harvard Medical School, Boston.
However, the link between higher HbA1c and better efficacy of metformin should be “considered carefully,” according to Dr. Nathan and his cocommittee members, who noted that the original criteria for the Diabetes Prevention Program study were based on glucose level, rather than HbA1c level.
Initial results of the Diabetes Prevention Program study indicated a particular benefit of metformin after an average of 2.8 years of follow-up in individuals with higher baseline fasting glucose levels and in women with a self-reported history of gestational diabetes (N Engl J Med. 2002 Feb 7;346[6]:393-403).
Those results prompted the American Diabetes Association and others to recommend consideration of metformin for diabetes prevention in individuals considered to be at high risk, Dr. Nathan and his colleagues noted. “This recommendation is further supported by the demonstrated cost savings of metformin in diabetes prevention.”
The Diabetes Prevention Program study originally included 3,234 high-risk participants enrolled between 1996 and 1999 and randomized to masked metformin, placebo, or intensive lifestyle intervention. The 15-year follow-up analysis considered the 2,155 individuals randomized to the metformin or placebo groups, of whom 1,861 (86%) chose to continue in the Diabetes Prevention Program Outcomes Study, in which they continued to receive metformin unmasked.
Over the 15 years, the incidence of diabetes development based on fasting or 2-hour glucose results was 17% lower in the metformin group, compared with the placebo group (hazard ratio, 0.83; or –1.25 cases per 100 person-years), according to Dr. Nathan and his colleagues.
For diabetes development based on HbA1c level, metformin was linked to a 36% reduction in risk, compared with placebo, or –1.67 cases per 100 person-years.
Higher baseline fasting plasma glucose (110-125 mg/dL vs. 95-109 mg/dL) was associated with a greater effect of metformin in reducing diabetes development over 15 years (P = .0004).
Metformin’s effect in reducing diabetes development was “nearly identical” in participants with an HbA1c of 6.0%-6.4%, compared with less than 6.0%, with HRs of 0.63 and 0.61, respectively; however, looking at rate differences, there was “substantial heterogeneity” between the groups, at –3.88 and –1.03 cases per 100 person-years, respectively, the investigators wrote.
For women with a history of gestational diabetes, metformin was linked to a 41% reduction in diabetes development, compared with placebo (P = .03); in women without gestational diabetes, the difference was a nonsignificant 6% reduction, compared with placebo. In terms of risk differences, this translated into a reduction of 4.57 cases per 100 person-years in women with gestational diabetes, compared with a reduction of just 0.38 cases in women without such a history. The authors noted that it is “complicated” to determine whether greater credence be given to the results based on glucose or those based on HbA1c.
On the one hand, the generalizability of the HbA1c analyses is adversely affected because the analyses were performed post hoc on a set of participants who had initially been selected for the study based on prediabetes defined by glucose. On the other, the HbA1c results may be more clinically relevant because “in many countries, oral glucose tolerance tests are not used routinely for the identification of persons at high risk for diabetes or with diabetes,” the authors wrote.
Continued follow-up of these patients will provide additional data on the potential long-term benefits of metformin use, such as the incidence of cardiovascular disease, cancer, and microvascular disease, the investigators concluded.
The National Institute of Diabetes and Digestive and Kidney Diseases and Department of Veterans Affairs, among others, funded the Diabetes Prevention Program and subsequent outcomes study. Lipha provided medication and LifeScan donated materials during the studies. Additional funding to the Diabetes Prevention Program was provided by Bristol-Myers Squibb and Parke-Davis.
SOURCE: Nathan DM et al. Diabetes Care. 2019 Mar 15. doi: 10.2337/dc18-1970.
Metformin is especially effective in diabetes prevention among persons with higher baseline fasting glucose, higher hemoglobin A1c (HbA1c), or a history of gestational diabetes, based on 15-year follow-up results from the Diabetes Prevention Program and the Diabetes Prevention Program Outcomes Study.
Beyond those subgroups, metformin remained effective regardless of how diabetes was diagnosed, with a risk reduction of up to 36%, according to a report published in Diabetes Care.
“These results should help to prioritize those groups at high risk of developing diabetes who will benefit most from being treated with metformin,” said the report’s writing committee, chaired by David M. Nathan, MD, professor of medicine at Harvard Medical School, Boston.
However, the link between higher HbA1c and better efficacy of metformin should be “considered carefully,” according to Dr. Nathan and his cocommittee members, who noted that the original criteria for the Diabetes Prevention Program study were based on glucose level, rather than HbA1c level.
Initial results of the Diabetes Prevention Program study indicated a particular benefit of metformin after an average of 2.8 years of follow-up in individuals with higher baseline fasting glucose levels and in women with a self-reported history of gestational diabetes (N Engl J Med. 2002 Feb 7;346[6]:393-403).
Those results prompted the American Diabetes Association and others to recommend consideration of metformin for diabetes prevention in individuals considered to be at high risk, Dr. Nathan and his colleagues noted. “This recommendation is further supported by the demonstrated cost savings of metformin in diabetes prevention.”
The Diabetes Prevention Program study originally included 3,234 high-risk participants enrolled between 1996 and 1999 and randomized to masked metformin, placebo, or intensive lifestyle intervention. The 15-year follow-up analysis considered the 2,155 individuals randomized to the metformin or placebo groups, of whom 1,861 (86%) chose to continue in the Diabetes Prevention Program Outcomes Study, in which they continued to receive metformin unmasked.
Over the 15 years, the incidence of diabetes development based on fasting or 2-hour glucose results was 17% lower in the metformin group, compared with the placebo group (hazard ratio, 0.83; or –1.25 cases per 100 person-years), according to Dr. Nathan and his colleagues.
For diabetes development based on HbA1c level, metformin was linked to a 36% reduction in risk, compared with placebo, or –1.67 cases per 100 person-years.
Higher baseline fasting plasma glucose (110-125 mg/dL vs. 95-109 mg/dL) was associated with a greater effect of metformin in reducing diabetes development over 15 years (P = .0004).
Metformin’s effect in reducing diabetes development was “nearly identical” in participants with an HbA1c of 6.0%-6.4%, compared with less than 6.0%, with HRs of 0.63 and 0.61, respectively; however, looking at rate differences, there was “substantial heterogeneity” between the groups, at –3.88 and –1.03 cases per 100 person-years, respectively, the investigators wrote.
For women with a history of gestational diabetes, metformin was linked to a 41% reduction in diabetes development, compared with placebo (P = .03); in women without gestational diabetes, the difference was a nonsignificant 6% reduction, compared with placebo. In terms of risk differences, this translated into a reduction of 4.57 cases per 100 person-years in women with gestational diabetes, compared with a reduction of just 0.38 cases in women without such a history. The authors noted that it is “complicated” to determine whether greater credence be given to the results based on glucose or those based on HbA1c.
On the one hand, the generalizability of the HbA1c analyses is adversely affected because the analyses were performed post hoc on a set of participants who had initially been selected for the study based on prediabetes defined by glucose. On the other, the HbA1c results may be more clinically relevant because “in many countries, oral glucose tolerance tests are not used routinely for the identification of persons at high risk for diabetes or with diabetes,” the authors wrote.
Continued follow-up of these patients will provide additional data on the potential long-term benefits of metformin use, such as the incidence of cardiovascular disease, cancer, and microvascular disease, the investigators concluded.
The National Institute of Diabetes and Digestive and Kidney Diseases and Department of Veterans Affairs, among others, funded the Diabetes Prevention Program and subsequent outcomes study. Lipha provided medication and LifeScan donated materials during the studies. Additional funding to the Diabetes Prevention Program was provided by Bristol-Myers Squibb and Parke-Davis.
SOURCE: Nathan DM et al. Diabetes Care. 2019 Mar 15. doi: 10.2337/dc18-1970.
Metformin is especially effective in diabetes prevention among persons with higher baseline fasting glucose, higher hemoglobin A1c (HbA1c), or a history of gestational diabetes, based on 15-year follow-up results from the Diabetes Prevention Program and the Diabetes Prevention Program Outcomes Study.
Beyond those subgroups, metformin remained effective regardless of how diabetes was diagnosed, with a risk reduction of up to 36%, according to a report published in Diabetes Care.
“These results should help to prioritize those groups at high risk of developing diabetes who will benefit most from being treated with metformin,” said the report’s writing committee, chaired by David M. Nathan, MD, professor of medicine at Harvard Medical School, Boston.
However, the link between higher HbA1c and better efficacy of metformin should be “considered carefully,” according to Dr. Nathan and his cocommittee members, who noted that the original criteria for the Diabetes Prevention Program study were based on glucose level, rather than HbA1c level.
Initial results of the Diabetes Prevention Program study indicated a particular benefit of metformin after an average of 2.8 years of follow-up in individuals with higher baseline fasting glucose levels and in women with a self-reported history of gestational diabetes (N Engl J Med. 2002 Feb 7;346[6]:393-403).
Those results prompted the American Diabetes Association and others to recommend consideration of metformin for diabetes prevention in individuals considered to be at high risk, Dr. Nathan and his colleagues noted. “This recommendation is further supported by the demonstrated cost savings of metformin in diabetes prevention.”
The Diabetes Prevention Program study originally included 3,234 high-risk participants enrolled between 1996 and 1999 and randomized to masked metformin, placebo, or intensive lifestyle intervention. The 15-year follow-up analysis considered the 2,155 individuals randomized to the metformin or placebo groups, of whom 1,861 (86%) chose to continue in the Diabetes Prevention Program Outcomes Study, in which they continued to receive metformin unmasked.
Over the 15 years, the incidence of diabetes development based on fasting or 2-hour glucose results was 17% lower in the metformin group, compared with the placebo group (hazard ratio, 0.83; or –1.25 cases per 100 person-years), according to Dr. Nathan and his colleagues.
For diabetes development based on HbA1c level, metformin was linked to a 36% reduction in risk, compared with placebo, or –1.67 cases per 100 person-years.
Higher baseline fasting plasma glucose (110-125 mg/dL vs. 95-109 mg/dL) was associated with a greater effect of metformin in reducing diabetes development over 15 years (P = .0004).
Metformin’s effect in reducing diabetes development was “nearly identical” in participants with an HbA1c of 6.0%-6.4%, compared with less than 6.0%, with HRs of 0.63 and 0.61, respectively; however, looking at rate differences, there was “substantial heterogeneity” between the groups, at –3.88 and –1.03 cases per 100 person-years, respectively, the investigators wrote.
For women with a history of gestational diabetes, metformin was linked to a 41% reduction in diabetes development, compared with placebo (P = .03); in women without gestational diabetes, the difference was a nonsignificant 6% reduction, compared with placebo. In terms of risk differences, this translated into a reduction of 4.57 cases per 100 person-years in women with gestational diabetes, compared with a reduction of just 0.38 cases in women without such a history. The authors noted that it is “complicated” to determine whether greater credence be given to the results based on glucose or those based on HbA1c.
On the one hand, the generalizability of the HbA1c analyses is adversely affected because the analyses were performed post hoc on a set of participants who had initially been selected for the study based on prediabetes defined by glucose. On the other, the HbA1c results may be more clinically relevant because “in many countries, oral glucose tolerance tests are not used routinely for the identification of persons at high risk for diabetes or with diabetes,” the authors wrote.
Continued follow-up of these patients will provide additional data on the potential long-term benefits of metformin use, such as the incidence of cardiovascular disease, cancer, and microvascular disease, the investigators concluded.
The National Institute of Diabetes and Digestive and Kidney Diseases and Department of Veterans Affairs, among others, funded the Diabetes Prevention Program and subsequent outcomes study. Lipha provided medication and LifeScan donated materials during the studies. Additional funding to the Diabetes Prevention Program was provided by Bristol-Myers Squibb and Parke-Davis.
SOURCE: Nathan DM et al. Diabetes Care. 2019 Mar 15. doi: 10.2337/dc18-1970.
FROM DIABETES CARE
Venetoclax and obinutuzumab induces deep responses in CLL
The combination of venetoclax and obinutuzumab provided high response rates and deep remissions regardless of cytogenetic risk factors in patients with chronic lymphocytic leukemia, according to recently reported results of a phase 1b study.
The regimen elicited high rates of undetectable minimal residual disease in peripheral blood and had an acceptable safety profile with manageable toxicities in the study reported in Blood, which included patients with previously untreated or relapsed/refractory chronic lymphocytic leukemia (CLL).
“The deep remission rates we observed with venetoclax-obinutuzumab have not been reported with previously available CLL treatments, including FCR [fludarabine, cyclophosphamide, and rituximab], which is currently considered the most efficacious regimen with limited-duration therapy,” wrote the investigators, led by Ian W. Flinn, MD, PhD, of Sarah Cannon Research Institute/Tennessee Oncology, Nashville.
Venetoclax-obinutuzumab combinations are meanwhile being tested in other studies – including the phase 3 CLL13 and CLL14 studies – which have enrolled previously untreated fit or unfit CLL patients, respectively.
“If the primary endpoints of these large-scale trials are met, venetoclax-obinutuzumab may become a new standard treatment option in [first-line] CLL, irrespective of clinical fitness,” Dr. Flinn and his colleagues wrote in their report.
The present phase 1b, dose-escalation study enrolled 32 patients who were previously untreated (median age, 63 years) and 46 patients who were relapsed or refractory to previous treatments (median age, 61 years).
Doses of venetoclax were escalated from 100 mg to 400 mg to determine its maximum tolerated dose when combined with obinutuzumab, the investigators wrote. Some patients received venetoclax first, while others received obinutuzumab first, for a total of 1 year of treatment.
The study confirmed favorable risk-benefit treatment used a dose of 400 mg venetoclax plus the standard dose of obinutuzumab, according to the researchers.
The overall best response rate was 95% for relapsed/refractory patients, including a 37% rate of complete response or complete response with incomplete marrow recovery. In previously untreated patients, the overall best response rate was 100%, including a 78% rate of complete responses by those criteria.
Undetectable minimal residual disease was observed in 64% of relapsed/refractory patients and 91% of previously untreated patients at 3 months after the last obinutuzumab dose, the investigators reported.
There were no dose-limiting toxicities in the study, no clinical tumor lysis syndrome, and no differences between the two schedules (venetoclax first or obinutuzumab first) in terms of adverse events, the investigators wrote.
Neutropenia was the most common serious (grade 3-4) adverse event, occurring in 58% of relapsed/refractory patients and 53% of patients treated in the first line. Grade 3-4 infections were seen in 29% and 13% of the relapsed/refractory and previously untreated patients, respectively.
There were no fatal infections among previously untreated patients, while three relapsed/refractory patients (7%) had fatal adverse events, including one case of acute respiratory failure in a patient with suspected Richter’s transformation, pneumonia in a patient with metastatic squamous cell lung carcinoma, and another case of pneumonia occurring about 3 months after the last dose of venetoclax.
Genentech and AbbVie provided financial support for the study. Dr. Flinn reported receiving research funding for his institution from Genentech, AbbVie, and several other companies.
SOURCE: Flinn IW et al. Blood. 2019 Mar 12. doi: 10.1182/blood-2019-01-896290.
The combination of venetoclax and obinutuzumab provided high response rates and deep remissions regardless of cytogenetic risk factors in patients with chronic lymphocytic leukemia, according to recently reported results of a phase 1b study.
The regimen elicited high rates of undetectable minimal residual disease in peripheral blood and had an acceptable safety profile with manageable toxicities in the study reported in Blood, which included patients with previously untreated or relapsed/refractory chronic lymphocytic leukemia (CLL).
“The deep remission rates we observed with venetoclax-obinutuzumab have not been reported with previously available CLL treatments, including FCR [fludarabine, cyclophosphamide, and rituximab], which is currently considered the most efficacious regimen with limited-duration therapy,” wrote the investigators, led by Ian W. Flinn, MD, PhD, of Sarah Cannon Research Institute/Tennessee Oncology, Nashville.
Venetoclax-obinutuzumab combinations are meanwhile being tested in other studies – including the phase 3 CLL13 and CLL14 studies – which have enrolled previously untreated fit or unfit CLL patients, respectively.
“If the primary endpoints of these large-scale trials are met, venetoclax-obinutuzumab may become a new standard treatment option in [first-line] CLL, irrespective of clinical fitness,” Dr. Flinn and his colleagues wrote in their report.
The present phase 1b, dose-escalation study enrolled 32 patients who were previously untreated (median age, 63 years) and 46 patients who were relapsed or refractory to previous treatments (median age, 61 years).
Doses of venetoclax were escalated from 100 mg to 400 mg to determine its maximum tolerated dose when combined with obinutuzumab, the investigators wrote. Some patients received venetoclax first, while others received obinutuzumab first, for a total of 1 year of treatment.
The study confirmed favorable risk-benefit treatment used a dose of 400 mg venetoclax plus the standard dose of obinutuzumab, according to the researchers.
The overall best response rate was 95% for relapsed/refractory patients, including a 37% rate of complete response or complete response with incomplete marrow recovery. In previously untreated patients, the overall best response rate was 100%, including a 78% rate of complete responses by those criteria.
Undetectable minimal residual disease was observed in 64% of relapsed/refractory patients and 91% of previously untreated patients at 3 months after the last obinutuzumab dose, the investigators reported.
There were no dose-limiting toxicities in the study, no clinical tumor lysis syndrome, and no differences between the two schedules (venetoclax first or obinutuzumab first) in terms of adverse events, the investigators wrote.
Neutropenia was the most common serious (grade 3-4) adverse event, occurring in 58% of relapsed/refractory patients and 53% of patients treated in the first line. Grade 3-4 infections were seen in 29% and 13% of the relapsed/refractory and previously untreated patients, respectively.
There were no fatal infections among previously untreated patients, while three relapsed/refractory patients (7%) had fatal adverse events, including one case of acute respiratory failure in a patient with suspected Richter’s transformation, pneumonia in a patient with metastatic squamous cell lung carcinoma, and another case of pneumonia occurring about 3 months after the last dose of venetoclax.
Genentech and AbbVie provided financial support for the study. Dr. Flinn reported receiving research funding for his institution from Genentech, AbbVie, and several other companies.
SOURCE: Flinn IW et al. Blood. 2019 Mar 12. doi: 10.1182/blood-2019-01-896290.
The combination of venetoclax and obinutuzumab provided high response rates and deep remissions regardless of cytogenetic risk factors in patients with chronic lymphocytic leukemia, according to recently reported results of a phase 1b study.
The regimen elicited high rates of undetectable minimal residual disease in peripheral blood and had an acceptable safety profile with manageable toxicities in the study reported in Blood, which included patients with previously untreated or relapsed/refractory chronic lymphocytic leukemia (CLL).
“The deep remission rates we observed with venetoclax-obinutuzumab have not been reported with previously available CLL treatments, including FCR [fludarabine, cyclophosphamide, and rituximab], which is currently considered the most efficacious regimen with limited-duration therapy,” wrote the investigators, led by Ian W. Flinn, MD, PhD, of Sarah Cannon Research Institute/Tennessee Oncology, Nashville.
Venetoclax-obinutuzumab combinations are meanwhile being tested in other studies – including the phase 3 CLL13 and CLL14 studies – which have enrolled previously untreated fit or unfit CLL patients, respectively.
“If the primary endpoints of these large-scale trials are met, venetoclax-obinutuzumab may become a new standard treatment option in [first-line] CLL, irrespective of clinical fitness,” Dr. Flinn and his colleagues wrote in their report.
The present phase 1b, dose-escalation study enrolled 32 patients who were previously untreated (median age, 63 years) and 46 patients who were relapsed or refractory to previous treatments (median age, 61 years).
Doses of venetoclax were escalated from 100 mg to 400 mg to determine its maximum tolerated dose when combined with obinutuzumab, the investigators wrote. Some patients received venetoclax first, while others received obinutuzumab first, for a total of 1 year of treatment.
The study confirmed favorable risk-benefit treatment used a dose of 400 mg venetoclax plus the standard dose of obinutuzumab, according to the researchers.
The overall best response rate was 95% for relapsed/refractory patients, including a 37% rate of complete response or complete response with incomplete marrow recovery. In previously untreated patients, the overall best response rate was 100%, including a 78% rate of complete responses by those criteria.
Undetectable minimal residual disease was observed in 64% of relapsed/refractory patients and 91% of previously untreated patients at 3 months after the last obinutuzumab dose, the investigators reported.
There were no dose-limiting toxicities in the study, no clinical tumor lysis syndrome, and no differences between the two schedules (venetoclax first or obinutuzumab first) in terms of adverse events, the investigators wrote.
Neutropenia was the most common serious (grade 3-4) adverse event, occurring in 58% of relapsed/refractory patients and 53% of patients treated in the first line. Grade 3-4 infections were seen in 29% and 13% of the relapsed/refractory and previously untreated patients, respectively.
There were no fatal infections among previously untreated patients, while three relapsed/refractory patients (7%) had fatal adverse events, including one case of acute respiratory failure in a patient with suspected Richter’s transformation, pneumonia in a patient with metastatic squamous cell lung carcinoma, and another case of pneumonia occurring about 3 months after the last dose of venetoclax.
Genentech and AbbVie provided financial support for the study. Dr. Flinn reported receiving research funding for his institution from Genentech, AbbVie, and several other companies.
SOURCE: Flinn IW et al. Blood. 2019 Mar 12. doi: 10.1182/blood-2019-01-896290.
FROM BLOOD
‘Difficult’ discussions reduced anxiety, depression in life-limiting cancer patients
A program to encourage difficult discussions between seriously ill patients and their oncologists reduced anxiety and depression in a recent randomized trial, but its impact on patient-centered outcomes were uncertain.
Goal-concordant care and peacefulness at the end of life, the coprimary study outcomes, were not significantly different between patients who received the quality improvement intervention and controls in the study, which included 91 clinicians providing care for 278 patients with advanced cancer.
However, it’s not clear whether the intervention, known as the Serious Illness Care Program (SICP), failed to improve those outcomes, or if there simply weren’t enough patients in the trial to detect a meaningful difference, according to investigators led by Rachelle Bernacki, MD, of Brigham and Women’s Hospital and the Harvard School of Public Health, Boston.
“Our challenges reflect the need in our field for patient-centered measures of communication that are agreed upon, validated, and demonstrably sensitive to communication interventions,” wrote Dr. Bernacki and her coinvestigators in a report on the study published in JAMA Internal Medicine.
However, the SICP intervention did clearly result in a larger number of serious-illness conversations that occurred earlier and were of higher quality, the investigators wrote in a separate report published in JAMA Oncology. In medical records reviewed after the patients’ deaths, 96% of those who received the intervention had a documented serious-illness conversation with their oncology clinician, compared with 79% of controls (P = .005), according to that report.
The conversations among SICP recipients occurred a median of 2.4 months earlier than controls, and had a greater focus on values and goals, prognosis and understanding of illness, and treatment preferences.
These outcomes are reassuring, since patients “want, require, and deserve” conversations about serious illness, regardless of their impact on measurable outcomes, the authors of an editorial published in JAMA Oncology wrote.
The SICP intervention included a communication guide for clinicians, who also participated in a 2.5-hour training session designed to improve their serious-illness conversation skills. Other aspects of the program for clinicians included email reminders before outpatient visits, a specialized EMR template, and personal coaching. The program also included patient tools, including a letter introducing the intervention and a guide for continuing the conversation with their family.
The study did not demonstrate a significant difference in peacefulness, as measured by the validated Peace, Equanimity, and Acceptance in the Cancer Experience questionnaire, or in goal-concordant care, which was measured by asking patients to select goals of importance, and then asking caregivers to rate whether those goals had been met at the end of life.
However, patients in the SICP group reported less anxiety and depression 14 weeks into the trial, according to the investigators. The proportion of patients reporting moderate to severe anxiety at that time point was 10.2% for the intervention group versus 5.0% for controls (P = .05), while the proportion reporting depression symptoms was 20.8% for the intervention versus 10.6% for controls (P = .04).
The anxiety reduction was maintained at 24 weeks, though the depression reduction was not, the investigators wrote, adding that there were no differences in survival between arms.
Taken together, these results suggest that oncology clinicians can discuss difficult topics without causing harm, and with potential benefit, the investigators wrote in a discussion of their results.
“Further development of serious illness communication interventions will require more reliable and well-accepted patient-centered outcome measures and additional testing of the effect on patients throughout their illness trajectory,” they concluded.
Dr. Bernacki reported no disclosures. Coauthor Susan D. Block, MD, reported compensation from Up to Date and Atul A. Gawande, MD, MPH, reported receiving compensation from health care writing and media and is employed by a health care venture formed by Amazon, Berkshire Hathaway, and JPMorgan Chase.
SOURCE: Bernacki R et al. JAMA Intern Med. 2018 Mar 14. doi: 10.1001/jamainternmed.2019.0077.
While results of this rigorous and innovative clinical trial are disappointing because of an apparent lack of impact on the primary outcomes of care, oncologists still must initiate serious illness conversations with advanced cancer patients at risk of dying in the foreseeable future, according to the authors of an editorial.
Doing so is important “not because this will necessarily improve outcomes, but because patients want, require, and deserve to know what is coming,” wrote Belinda E. Kiely, MBBS, PhD, FRACP, and Martin R. Stockler, MBBS, MSc, FRACP.
Those difficult conversations should not stop at discussing the limits of care, but should include a discussion of the patient’s preferences, priorities, and values, Dr. Kiely and Dr. Stockler wrote, adding that they should be documented in the EMR to ensure they are accessible to other health care providers.
“If nothing else, oncologists should be reassured that having these conversations is unlikely to increase anxiety or depression in their patients,” wrote the editorial authors, referencing the significantly reduced incidence of those secondary endpoints in the study.
However, conversations alone may not be enough to improve other patient-centered outcomes, based on the inability of this trial to demonstrate significant improvements in goal-centered care or peacefulness at the end of life.
Moreover, building this Serious Illness Care Program intervention into a health system could be complicated and may require significant resources.
“Simple, pragmatic, and effective tactics are needed to ensure greater generalizability and widespread applicability of such programs,” the authors concluded.
Dr. Kiely and Dr. Stockler are with the National Health and Medical Research Council Clinical Trials Centre at the University of Sydney. Their editorial appears in JAMA Oncology. Dr. Stockler reported grants outside the submitted work from Astellas, Amgen, AstraZeneca, Cancer Australia, Celgene, Bionomics, Bayer, Medivation, Merck, National Health and Medical Research Council Australia, Pfizer, Roche, Sanofi, and Tilray.
While results of this rigorous and innovative clinical trial are disappointing because of an apparent lack of impact on the primary outcomes of care, oncologists still must initiate serious illness conversations with advanced cancer patients at risk of dying in the foreseeable future, according to the authors of an editorial.
Doing so is important “not because this will necessarily improve outcomes, but because patients want, require, and deserve to know what is coming,” wrote Belinda E. Kiely, MBBS, PhD, FRACP, and Martin R. Stockler, MBBS, MSc, FRACP.
Those difficult conversations should not stop at discussing the limits of care, but should include a discussion of the patient’s preferences, priorities, and values, Dr. Kiely and Dr. Stockler wrote, adding that they should be documented in the EMR to ensure they are accessible to other health care providers.
“If nothing else, oncologists should be reassured that having these conversations is unlikely to increase anxiety or depression in their patients,” wrote the editorial authors, referencing the significantly reduced incidence of those secondary endpoints in the study.
However, conversations alone may not be enough to improve other patient-centered outcomes, based on the inability of this trial to demonstrate significant improvements in goal-centered care or peacefulness at the end of life.
Moreover, building this Serious Illness Care Program intervention into a health system could be complicated and may require significant resources.
“Simple, pragmatic, and effective tactics are needed to ensure greater generalizability and widespread applicability of such programs,” the authors concluded.
Dr. Kiely and Dr. Stockler are with the National Health and Medical Research Council Clinical Trials Centre at the University of Sydney. Their editorial appears in JAMA Oncology. Dr. Stockler reported grants outside the submitted work from Astellas, Amgen, AstraZeneca, Cancer Australia, Celgene, Bionomics, Bayer, Medivation, Merck, National Health and Medical Research Council Australia, Pfizer, Roche, Sanofi, and Tilray.
While results of this rigorous and innovative clinical trial are disappointing because of an apparent lack of impact on the primary outcomes of care, oncologists still must initiate serious illness conversations with advanced cancer patients at risk of dying in the foreseeable future, according to the authors of an editorial.
Doing so is important “not because this will necessarily improve outcomes, but because patients want, require, and deserve to know what is coming,” wrote Belinda E. Kiely, MBBS, PhD, FRACP, and Martin R. Stockler, MBBS, MSc, FRACP.
Those difficult conversations should not stop at discussing the limits of care, but should include a discussion of the patient’s preferences, priorities, and values, Dr. Kiely and Dr. Stockler wrote, adding that they should be documented in the EMR to ensure they are accessible to other health care providers.
“If nothing else, oncologists should be reassured that having these conversations is unlikely to increase anxiety or depression in their patients,” wrote the editorial authors, referencing the significantly reduced incidence of those secondary endpoints in the study.
However, conversations alone may not be enough to improve other patient-centered outcomes, based on the inability of this trial to demonstrate significant improvements in goal-centered care or peacefulness at the end of life.
Moreover, building this Serious Illness Care Program intervention into a health system could be complicated and may require significant resources.
“Simple, pragmatic, and effective tactics are needed to ensure greater generalizability and widespread applicability of such programs,” the authors concluded.
Dr. Kiely and Dr. Stockler are with the National Health and Medical Research Council Clinical Trials Centre at the University of Sydney. Their editorial appears in JAMA Oncology. Dr. Stockler reported grants outside the submitted work from Astellas, Amgen, AstraZeneca, Cancer Australia, Celgene, Bionomics, Bayer, Medivation, Merck, National Health and Medical Research Council Australia, Pfizer, Roche, Sanofi, and Tilray.
A program to encourage difficult discussions between seriously ill patients and their oncologists reduced anxiety and depression in a recent randomized trial, but its impact on patient-centered outcomes were uncertain.
Goal-concordant care and peacefulness at the end of life, the coprimary study outcomes, were not significantly different between patients who received the quality improvement intervention and controls in the study, which included 91 clinicians providing care for 278 patients with advanced cancer.
However, it’s not clear whether the intervention, known as the Serious Illness Care Program (SICP), failed to improve those outcomes, or if there simply weren’t enough patients in the trial to detect a meaningful difference, according to investigators led by Rachelle Bernacki, MD, of Brigham and Women’s Hospital and the Harvard School of Public Health, Boston.
“Our challenges reflect the need in our field for patient-centered measures of communication that are agreed upon, validated, and demonstrably sensitive to communication interventions,” wrote Dr. Bernacki and her coinvestigators in a report on the study published in JAMA Internal Medicine.
However, the SICP intervention did clearly result in a larger number of serious-illness conversations that occurred earlier and were of higher quality, the investigators wrote in a separate report published in JAMA Oncology. In medical records reviewed after the patients’ deaths, 96% of those who received the intervention had a documented serious-illness conversation with their oncology clinician, compared with 79% of controls (P = .005), according to that report.
The conversations among SICP recipients occurred a median of 2.4 months earlier than controls, and had a greater focus on values and goals, prognosis and understanding of illness, and treatment preferences.
These outcomes are reassuring, since patients “want, require, and deserve” conversations about serious illness, regardless of their impact on measurable outcomes, the authors of an editorial published in JAMA Oncology wrote.
The SICP intervention included a communication guide for clinicians, who also participated in a 2.5-hour training session designed to improve their serious-illness conversation skills. Other aspects of the program for clinicians included email reminders before outpatient visits, a specialized EMR template, and personal coaching. The program also included patient tools, including a letter introducing the intervention and a guide for continuing the conversation with their family.
The study did not demonstrate a significant difference in peacefulness, as measured by the validated Peace, Equanimity, and Acceptance in the Cancer Experience questionnaire, or in goal-concordant care, which was measured by asking patients to select goals of importance, and then asking caregivers to rate whether those goals had been met at the end of life.
However, patients in the SICP group reported less anxiety and depression 14 weeks into the trial, according to the investigators. The proportion of patients reporting moderate to severe anxiety at that time point was 10.2% for the intervention group versus 5.0% for controls (P = .05), while the proportion reporting depression symptoms was 20.8% for the intervention versus 10.6% for controls (P = .04).
The anxiety reduction was maintained at 24 weeks, though the depression reduction was not, the investigators wrote, adding that there were no differences in survival between arms.
Taken together, these results suggest that oncology clinicians can discuss difficult topics without causing harm, and with potential benefit, the investigators wrote in a discussion of their results.
“Further development of serious illness communication interventions will require more reliable and well-accepted patient-centered outcome measures and additional testing of the effect on patients throughout their illness trajectory,” they concluded.
Dr. Bernacki reported no disclosures. Coauthor Susan D. Block, MD, reported compensation from Up to Date and Atul A. Gawande, MD, MPH, reported receiving compensation from health care writing and media and is employed by a health care venture formed by Amazon, Berkshire Hathaway, and JPMorgan Chase.
SOURCE: Bernacki R et al. JAMA Intern Med. 2018 Mar 14. doi: 10.1001/jamainternmed.2019.0077.
A program to encourage difficult discussions between seriously ill patients and their oncologists reduced anxiety and depression in a recent randomized trial, but its impact on patient-centered outcomes were uncertain.
Goal-concordant care and peacefulness at the end of life, the coprimary study outcomes, were not significantly different between patients who received the quality improvement intervention and controls in the study, which included 91 clinicians providing care for 278 patients with advanced cancer.
However, it’s not clear whether the intervention, known as the Serious Illness Care Program (SICP), failed to improve those outcomes, or if there simply weren’t enough patients in the trial to detect a meaningful difference, according to investigators led by Rachelle Bernacki, MD, of Brigham and Women’s Hospital and the Harvard School of Public Health, Boston.
“Our challenges reflect the need in our field for patient-centered measures of communication that are agreed upon, validated, and demonstrably sensitive to communication interventions,” wrote Dr. Bernacki and her coinvestigators in a report on the study published in JAMA Internal Medicine.
However, the SICP intervention did clearly result in a larger number of serious-illness conversations that occurred earlier and were of higher quality, the investigators wrote in a separate report published in JAMA Oncology. In medical records reviewed after the patients’ deaths, 96% of those who received the intervention had a documented serious-illness conversation with their oncology clinician, compared with 79% of controls (P = .005), according to that report.
The conversations among SICP recipients occurred a median of 2.4 months earlier than controls, and had a greater focus on values and goals, prognosis and understanding of illness, and treatment preferences.
These outcomes are reassuring, since patients “want, require, and deserve” conversations about serious illness, regardless of their impact on measurable outcomes, the authors of an editorial published in JAMA Oncology wrote.
The SICP intervention included a communication guide for clinicians, who also participated in a 2.5-hour training session designed to improve their serious-illness conversation skills. Other aspects of the program for clinicians included email reminders before outpatient visits, a specialized EMR template, and personal coaching. The program also included patient tools, including a letter introducing the intervention and a guide for continuing the conversation with their family.
The study did not demonstrate a significant difference in peacefulness, as measured by the validated Peace, Equanimity, and Acceptance in the Cancer Experience questionnaire, or in goal-concordant care, which was measured by asking patients to select goals of importance, and then asking caregivers to rate whether those goals had been met at the end of life.
However, patients in the SICP group reported less anxiety and depression 14 weeks into the trial, according to the investigators. The proportion of patients reporting moderate to severe anxiety at that time point was 10.2% for the intervention group versus 5.0% for controls (P = .05), while the proportion reporting depression symptoms was 20.8% for the intervention versus 10.6% for controls (P = .04).
The anxiety reduction was maintained at 24 weeks, though the depression reduction was not, the investigators wrote, adding that there were no differences in survival between arms.
Taken together, these results suggest that oncology clinicians can discuss difficult topics without causing harm, and with potential benefit, the investigators wrote in a discussion of their results.
“Further development of serious illness communication interventions will require more reliable and well-accepted patient-centered outcome measures and additional testing of the effect on patients throughout their illness trajectory,” they concluded.
Dr. Bernacki reported no disclosures. Coauthor Susan D. Block, MD, reported compensation from Up to Date and Atul A. Gawande, MD, MPH, reported receiving compensation from health care writing and media and is employed by a health care venture formed by Amazon, Berkshire Hathaway, and JPMorgan Chase.
SOURCE: Bernacki R et al. JAMA Intern Med. 2018 Mar 14. doi: 10.1001/jamainternmed.2019.0077.
FROM JAMA INTERNAL MEDICINE
Bleeding disorders don’t carry increased risks for patients undergoing endoscopy
When managed by an experienced team, patients with inherited bleeding disorders undergoing gastrointestinal endoscopy are not at increased bleeding risk, according to researchers reporting the largest series of such patients to date.
The postendoscopy bleeding rate was less than 1% for the patients in this series, many of whom underwent high-risk procedures or had comorbid conditions putting them at risk of bleeding, the researchers reported.
The rate of colonoscopic postpolypectomy bleeding was less than 5%, which is comparable to the general population rate for such high-risk procedures, said investigator Marcel Tomaszewski, MD, of McGill University, Montreal, and colleagues.
Those results favor the use of the “interdisciplinary approach provided by a hemophilia treatment center, communication between services, and the use of periprocedure prophylaxis including tranexamic acid,” Dr. Tomaszewski and coinvestigators said in their report in Haemophilia.
The study cohort included 48 individuals undergoing a total of 104 endoscopies, which is believed to be the largest case series of digestive endoscopy procedures ever reported in patients with congenital bleeding disorders, according to the researchers.
Hemophilia A and von Willebrand disease were the most common bleeding disorders among these patients, accounting for 49 and 40 of the 104 procedures, respectively. The remaining 17 procedures were performed in patients with factor XI deficiency, hemophilia B, or factor VII deficiency.
Before their endoscopies, patients received bleeding prophylaxis, which consisted of combinations of recombinant factor for hemophilia patients, plasma-derived factor for von Willebrand disease patients, desmopressin, and tranexamic acid.
The rate of bleeding within 72 hours of the endoscopic procedure was 0.96% (95% confidence interval, 0.17%-5.25%). The bleeding rate for hemophilia A patients, regardless of severity, was 2.2%, while the rate for hemophilia B, von Willebrand disease, factor VII deficiency and factor XI deficiency was 0%.
The only endoscopic procedures associated with bleeding were colonoscopy, with a bleeding rate of 2%, and colonoscopy with polypectomy, which had a 4.8% bleeding rate, they added, noting that the reported rate of postpolypectomy bleeding in the general population ranges between 0.3% and 10%.
“The very low incidence of bleeding adverse events limited further planned inferential statistical analysis,” the researchers wrote.
These findings stand in contrast to some previous reports, including one series of 19 patients with hemophilia in which 31% experienced gastrointestinal bleeding after colonoscopy polypectomy, despite preprocedure prophylaxis.
“Our approach, particularly with the addition of tranexamic acid, and our patient mix may explain the lower bleeding rate,” they wrote.
The most common indications for endoscopy in the present report were anemia, colorectal cancer screening or polyp surveillance, upper GI symptoms, and screening or surveillance of varices.
Many patients had conditions that might predispose them to bleeding, investigators said. Most commonly, those conditions included hepatitis C virus infection, cirrhosis, esophageal varices, and previous gastrointestinal bleeding.
Dr. Tomaszewski reported that he had no potential conflicts of interest related to the research. Coauthors reported financial disclosures related to AbbVie, Pfizer, Takeda, Janssen, and others.
SOURCE: Tomaszewski M et al. Haemophilia. 2019 Feb 12. doi: 10.1111/hae.13691
When managed by an experienced team, patients with inherited bleeding disorders undergoing gastrointestinal endoscopy are not at increased bleeding risk, according to researchers reporting the largest series of such patients to date.
The postendoscopy bleeding rate was less than 1% for the patients in this series, many of whom underwent high-risk procedures or had comorbid conditions putting them at risk of bleeding, the researchers reported.
The rate of colonoscopic postpolypectomy bleeding was less than 5%, which is comparable to the general population rate for such high-risk procedures, said investigator Marcel Tomaszewski, MD, of McGill University, Montreal, and colleagues.
Those results favor the use of the “interdisciplinary approach provided by a hemophilia treatment center, communication between services, and the use of periprocedure prophylaxis including tranexamic acid,” Dr. Tomaszewski and coinvestigators said in their report in Haemophilia.
The study cohort included 48 individuals undergoing a total of 104 endoscopies, which is believed to be the largest case series of digestive endoscopy procedures ever reported in patients with congenital bleeding disorders, according to the researchers.
Hemophilia A and von Willebrand disease were the most common bleeding disorders among these patients, accounting for 49 and 40 of the 104 procedures, respectively. The remaining 17 procedures were performed in patients with factor XI deficiency, hemophilia B, or factor VII deficiency.
Before their endoscopies, patients received bleeding prophylaxis, which consisted of combinations of recombinant factor for hemophilia patients, plasma-derived factor for von Willebrand disease patients, desmopressin, and tranexamic acid.
The rate of bleeding within 72 hours of the endoscopic procedure was 0.96% (95% confidence interval, 0.17%-5.25%). The bleeding rate for hemophilia A patients, regardless of severity, was 2.2%, while the rate for hemophilia B, von Willebrand disease, factor VII deficiency and factor XI deficiency was 0%.
The only endoscopic procedures associated with bleeding were colonoscopy, with a bleeding rate of 2%, and colonoscopy with polypectomy, which had a 4.8% bleeding rate, they added, noting that the reported rate of postpolypectomy bleeding in the general population ranges between 0.3% and 10%.
“The very low incidence of bleeding adverse events limited further planned inferential statistical analysis,” the researchers wrote.
These findings stand in contrast to some previous reports, including one series of 19 patients with hemophilia in which 31% experienced gastrointestinal bleeding after colonoscopy polypectomy, despite preprocedure prophylaxis.
“Our approach, particularly with the addition of tranexamic acid, and our patient mix may explain the lower bleeding rate,” they wrote.
The most common indications for endoscopy in the present report were anemia, colorectal cancer screening or polyp surveillance, upper GI symptoms, and screening or surveillance of varices.
Many patients had conditions that might predispose them to bleeding, investigators said. Most commonly, those conditions included hepatitis C virus infection, cirrhosis, esophageal varices, and previous gastrointestinal bleeding.
Dr. Tomaszewski reported that he had no potential conflicts of interest related to the research. Coauthors reported financial disclosures related to AbbVie, Pfizer, Takeda, Janssen, and others.
SOURCE: Tomaszewski M et al. Haemophilia. 2019 Feb 12. doi: 10.1111/hae.13691
When managed by an experienced team, patients with inherited bleeding disorders undergoing gastrointestinal endoscopy are not at increased bleeding risk, according to researchers reporting the largest series of such patients to date.
The postendoscopy bleeding rate was less than 1% for the patients in this series, many of whom underwent high-risk procedures or had comorbid conditions putting them at risk of bleeding, the researchers reported.
The rate of colonoscopic postpolypectomy bleeding was less than 5%, which is comparable to the general population rate for such high-risk procedures, said investigator Marcel Tomaszewski, MD, of McGill University, Montreal, and colleagues.
Those results favor the use of the “interdisciplinary approach provided by a hemophilia treatment center, communication between services, and the use of periprocedure prophylaxis including tranexamic acid,” Dr. Tomaszewski and coinvestigators said in their report in Haemophilia.
The study cohort included 48 individuals undergoing a total of 104 endoscopies, which is believed to be the largest case series of digestive endoscopy procedures ever reported in patients with congenital bleeding disorders, according to the researchers.
Hemophilia A and von Willebrand disease were the most common bleeding disorders among these patients, accounting for 49 and 40 of the 104 procedures, respectively. The remaining 17 procedures were performed in patients with factor XI deficiency, hemophilia B, or factor VII deficiency.
Before their endoscopies, patients received bleeding prophylaxis, which consisted of combinations of recombinant factor for hemophilia patients, plasma-derived factor for von Willebrand disease patients, desmopressin, and tranexamic acid.
The rate of bleeding within 72 hours of the endoscopic procedure was 0.96% (95% confidence interval, 0.17%-5.25%). The bleeding rate for hemophilia A patients, regardless of severity, was 2.2%, while the rate for hemophilia B, von Willebrand disease, factor VII deficiency and factor XI deficiency was 0%.
The only endoscopic procedures associated with bleeding were colonoscopy, with a bleeding rate of 2%, and colonoscopy with polypectomy, which had a 4.8% bleeding rate, they added, noting that the reported rate of postpolypectomy bleeding in the general population ranges between 0.3% and 10%.
“The very low incidence of bleeding adverse events limited further planned inferential statistical analysis,” the researchers wrote.
These findings stand in contrast to some previous reports, including one series of 19 patients with hemophilia in which 31% experienced gastrointestinal bleeding after colonoscopy polypectomy, despite preprocedure prophylaxis.
“Our approach, particularly with the addition of tranexamic acid, and our patient mix may explain the lower bleeding rate,” they wrote.
The most common indications for endoscopy in the present report were anemia, colorectal cancer screening or polyp surveillance, upper GI symptoms, and screening or surveillance of varices.
Many patients had conditions that might predispose them to bleeding, investigators said. Most commonly, those conditions included hepatitis C virus infection, cirrhosis, esophageal varices, and previous gastrointestinal bleeding.
Dr. Tomaszewski reported that he had no potential conflicts of interest related to the research. Coauthors reported financial disclosures related to AbbVie, Pfizer, Takeda, Janssen, and others.
SOURCE: Tomaszewski M et al. Haemophilia. 2019 Feb 12. doi: 10.1111/hae.13691
FROM HAEMOPHILIA
Anti-CD45 conditioning looks safe, feasible in relapsed AML
HOUSTON – A novel anti-CD45 targeted conditioning regimen is feasible for use in older patients with relapsed or refractory acute myeloid leukemia undergoing transplant, according to preliminary results of a randomized, phase 3 trial.
Treatment with iodine-131 apamistamab (Iomab-B) has thus far has resulted in successful engraftment for all patients who have received it and gone on to transplant, despite active disease and high bone marrow blast burden prior to transplantation, according to Sergio A. Giralt, MD, of Memorial Sloan Kettering Cancer Center, New York.
There has been no nonrelapse mortality related to the novel regimen in the ongoing trial, which compares Iomab-B as targeted conditioning prior to allogeneic hematopoietic stem cell transplant (HCT) with standard of care regimens, Dr. Giralt said in an update on the trial, known as SIERRA.
SIERRA is the only ongoing, randomized, phase 3 clinical trial to offer a transplant option in patients aged 55 years or older with active relapsed or refractory acute myeloid leukemia (AML), Dr. Giralt said at the Transplantation & Cellular Therapy Meetings.
“This is an underserved population in which traditional transplant techniques have very poor results, and there are limited options for patients with active disease,” Dr. Giralt said. “Of note, many transplant centers today do not consider these patients eligible for transplant.”
A total of 150 patients are to be enrolled in SIERRA and randomized either to investigator’s choice of salvage induction chemotherapy including approved targeted agents or to the experimental arm, which consists of an individualized dose of Iomab-B 12 days prior to HCT with fludarabine and total body irradiation as transplant conditioning.
Dr. Giralt presented an update on the first 38 patients in SIERRA, representing 25% of the total enrollment target.
Of 18 patients randomized to Iomab-B and transplanted, the median number of days to absolute neutrophil count engraftment was 13, Dr. Giralt said.
In the control arm, 15 of 19 (79%) failed to achieve complete remission, and of those 10 crossed over to receive Iomab-B and transplant. Days to engraftment, full donor chimerism, and dose delivered to the bone marrow were all similar in the crossover group, compared with those initially randomized to the novel therapy.
Nonhematologic grade 3 or 4 toxicities were similar between the Iomab-B arm and the conventional care arm, and included febrile neutropenia, stomatitis, and other side effects typical for these patients.
There were no grade 3 or 4 Iomab-B infusion-related reactions, and four mild cases of chronic graft-versus-host disease occurred in Iomab-B treated patients.
Nonrelapse mortality was “extremely low” with no cases in the 100 days post transplant in those initially randomized to Iomab-B, and only one case in a crossover patient, Dr. Giralt said.
“These results are encouraging, and can broaden transplant eligibility and improve outcomes,” he added.
The meeting is held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
The SIERRA study is supported by Actinium Pharmaceuticals. Dr. Giralt reported disclosures related to Actinium and several other companies.
SOURCE: Giralt SA et al. TCT 2019, Abstract LBA3.
HOUSTON – A novel anti-CD45 targeted conditioning regimen is feasible for use in older patients with relapsed or refractory acute myeloid leukemia undergoing transplant, according to preliminary results of a randomized, phase 3 trial.
Treatment with iodine-131 apamistamab (Iomab-B) has thus far has resulted in successful engraftment for all patients who have received it and gone on to transplant, despite active disease and high bone marrow blast burden prior to transplantation, according to Sergio A. Giralt, MD, of Memorial Sloan Kettering Cancer Center, New York.
There has been no nonrelapse mortality related to the novel regimen in the ongoing trial, which compares Iomab-B as targeted conditioning prior to allogeneic hematopoietic stem cell transplant (HCT) with standard of care regimens, Dr. Giralt said in an update on the trial, known as SIERRA.
SIERRA is the only ongoing, randomized, phase 3 clinical trial to offer a transplant option in patients aged 55 years or older with active relapsed or refractory acute myeloid leukemia (AML), Dr. Giralt said at the Transplantation & Cellular Therapy Meetings.
“This is an underserved population in which traditional transplant techniques have very poor results, and there are limited options for patients with active disease,” Dr. Giralt said. “Of note, many transplant centers today do not consider these patients eligible for transplant.”
A total of 150 patients are to be enrolled in SIERRA and randomized either to investigator’s choice of salvage induction chemotherapy including approved targeted agents or to the experimental arm, which consists of an individualized dose of Iomab-B 12 days prior to HCT with fludarabine and total body irradiation as transplant conditioning.
Dr. Giralt presented an update on the first 38 patients in SIERRA, representing 25% of the total enrollment target.
Of 18 patients randomized to Iomab-B and transplanted, the median number of days to absolute neutrophil count engraftment was 13, Dr. Giralt said.
In the control arm, 15 of 19 (79%) failed to achieve complete remission, and of those 10 crossed over to receive Iomab-B and transplant. Days to engraftment, full donor chimerism, and dose delivered to the bone marrow were all similar in the crossover group, compared with those initially randomized to the novel therapy.
Nonhematologic grade 3 or 4 toxicities were similar between the Iomab-B arm and the conventional care arm, and included febrile neutropenia, stomatitis, and other side effects typical for these patients.
There were no grade 3 or 4 Iomab-B infusion-related reactions, and four mild cases of chronic graft-versus-host disease occurred in Iomab-B treated patients.
Nonrelapse mortality was “extremely low” with no cases in the 100 days post transplant in those initially randomized to Iomab-B, and only one case in a crossover patient, Dr. Giralt said.
“These results are encouraging, and can broaden transplant eligibility and improve outcomes,” he added.
The meeting is held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
The SIERRA study is supported by Actinium Pharmaceuticals. Dr. Giralt reported disclosures related to Actinium and several other companies.
SOURCE: Giralt SA et al. TCT 2019, Abstract LBA3.
HOUSTON – A novel anti-CD45 targeted conditioning regimen is feasible for use in older patients with relapsed or refractory acute myeloid leukemia undergoing transplant, according to preliminary results of a randomized, phase 3 trial.
Treatment with iodine-131 apamistamab (Iomab-B) has thus far has resulted in successful engraftment for all patients who have received it and gone on to transplant, despite active disease and high bone marrow blast burden prior to transplantation, according to Sergio A. Giralt, MD, of Memorial Sloan Kettering Cancer Center, New York.
There has been no nonrelapse mortality related to the novel regimen in the ongoing trial, which compares Iomab-B as targeted conditioning prior to allogeneic hematopoietic stem cell transplant (HCT) with standard of care regimens, Dr. Giralt said in an update on the trial, known as SIERRA.
SIERRA is the only ongoing, randomized, phase 3 clinical trial to offer a transplant option in patients aged 55 years or older with active relapsed or refractory acute myeloid leukemia (AML), Dr. Giralt said at the Transplantation & Cellular Therapy Meetings.
“This is an underserved population in which traditional transplant techniques have very poor results, and there are limited options for patients with active disease,” Dr. Giralt said. “Of note, many transplant centers today do not consider these patients eligible for transplant.”
A total of 150 patients are to be enrolled in SIERRA and randomized either to investigator’s choice of salvage induction chemotherapy including approved targeted agents or to the experimental arm, which consists of an individualized dose of Iomab-B 12 days prior to HCT with fludarabine and total body irradiation as transplant conditioning.
Dr. Giralt presented an update on the first 38 patients in SIERRA, representing 25% of the total enrollment target.
Of 18 patients randomized to Iomab-B and transplanted, the median number of days to absolute neutrophil count engraftment was 13, Dr. Giralt said.
In the control arm, 15 of 19 (79%) failed to achieve complete remission, and of those 10 crossed over to receive Iomab-B and transplant. Days to engraftment, full donor chimerism, and dose delivered to the bone marrow were all similar in the crossover group, compared with those initially randomized to the novel therapy.
Nonhematologic grade 3 or 4 toxicities were similar between the Iomab-B arm and the conventional care arm, and included febrile neutropenia, stomatitis, and other side effects typical for these patients.
There were no grade 3 or 4 Iomab-B infusion-related reactions, and four mild cases of chronic graft-versus-host disease occurred in Iomab-B treated patients.
Nonrelapse mortality was “extremely low” with no cases in the 100 days post transplant in those initially randomized to Iomab-B, and only one case in a crossover patient, Dr. Giralt said.
“These results are encouraging, and can broaden transplant eligibility and improve outcomes,” he added.
The meeting is held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
The SIERRA study is supported by Actinium Pharmaceuticals. Dr. Giralt reported disclosures related to Actinium and several other companies.
SOURCE: Giralt SA et al. TCT 2019, Abstract LBA3.
REPORTING FROM TCT 2019