User login
Transfusions, readmissions higher for patients with CLL after cardiac surgery
Patients with chronic lymphocytic leukemia have similar outcomes following cardiac operations as patients without CLL, but commonly require more blood transfusions, according to the results of retrospective cohort study using the 2010-2017 Nationwide Readmissions Database (NRD).
The researchers assessed all adult patients undergoing elective coronary artery bypass grafting, valve repair, or valve replacement as identified using the NRD.
Patients were stratified by history of CLL and the incidence of in-hospital mortality, perioperative complications, blood transfusions, and readmission within 90 days were examined. A 3:1 nearest-neighbor matching was performed between patients with and without CLL for all primary and secondary outcomes of interest, according to the report, published online in Annals of Thoracic Surgery.
Comparable results
A total of 1,250,882 patients in the database were found who underwent cardiac operations. Of these, 0.23% had a diagnosis of CLL. Among 11,237 propensity-matched patients, those with CLL had similar rates of in-hospital mortality (3.8% vs. 2.6%, P = .08) and perioperative complications (33.4% vs. 33.6%, P = .92), compared with their non-CLL counterparts. However, the incidence of infection was comparable (8.5% vs. 9.4%, P = .38).
However, patients with CLL required blood transfusions more frequently (33.7% vs. 28.4%, P = .003) than did patients without CLL. In addition, patients with CLL were more likely to be readmitted within 90 days of discharge, compared with their counterparts, and “respiratory reasons, including pneumonia, contributed significantly to the readmission burden in this cohort,” the researchers, led by Josef Madrigal, BS, of the University of California, Los Angeles, stated.
“The inherent risk of transfusion and the possible benefits of blood conservation interventions must be considered in this patient population. Increased risk of rehospitalization in patients with CLL suggests the need for measures aimed at mitigating the risk of respiratory complications,” the researchers concluded.
There were no conflicts of interest reported in the article.
Patients with chronic lymphocytic leukemia have similar outcomes following cardiac operations as patients without CLL, but commonly require more blood transfusions, according to the results of retrospective cohort study using the 2010-2017 Nationwide Readmissions Database (NRD).
The researchers assessed all adult patients undergoing elective coronary artery bypass grafting, valve repair, or valve replacement as identified using the NRD.
Patients were stratified by history of CLL and the incidence of in-hospital mortality, perioperative complications, blood transfusions, and readmission within 90 days were examined. A 3:1 nearest-neighbor matching was performed between patients with and without CLL for all primary and secondary outcomes of interest, according to the report, published online in Annals of Thoracic Surgery.
Comparable results
A total of 1,250,882 patients in the database were found who underwent cardiac operations. Of these, 0.23% had a diagnosis of CLL. Among 11,237 propensity-matched patients, those with CLL had similar rates of in-hospital mortality (3.8% vs. 2.6%, P = .08) and perioperative complications (33.4% vs. 33.6%, P = .92), compared with their non-CLL counterparts. However, the incidence of infection was comparable (8.5% vs. 9.4%, P = .38).
However, patients with CLL required blood transfusions more frequently (33.7% vs. 28.4%, P = .003) than did patients without CLL. In addition, patients with CLL were more likely to be readmitted within 90 days of discharge, compared with their counterparts, and “respiratory reasons, including pneumonia, contributed significantly to the readmission burden in this cohort,” the researchers, led by Josef Madrigal, BS, of the University of California, Los Angeles, stated.
“The inherent risk of transfusion and the possible benefits of blood conservation interventions must be considered in this patient population. Increased risk of rehospitalization in patients with CLL suggests the need for measures aimed at mitigating the risk of respiratory complications,” the researchers concluded.
There were no conflicts of interest reported in the article.
Patients with chronic lymphocytic leukemia have similar outcomes following cardiac operations as patients without CLL, but commonly require more blood transfusions, according to the results of retrospective cohort study using the 2010-2017 Nationwide Readmissions Database (NRD).
The researchers assessed all adult patients undergoing elective coronary artery bypass grafting, valve repair, or valve replacement as identified using the NRD.
Patients were stratified by history of CLL and the incidence of in-hospital mortality, perioperative complications, blood transfusions, and readmission within 90 days were examined. A 3:1 nearest-neighbor matching was performed between patients with and without CLL for all primary and secondary outcomes of interest, according to the report, published online in Annals of Thoracic Surgery.
Comparable results
A total of 1,250,882 patients in the database were found who underwent cardiac operations. Of these, 0.23% had a diagnosis of CLL. Among 11,237 propensity-matched patients, those with CLL had similar rates of in-hospital mortality (3.8% vs. 2.6%, P = .08) and perioperative complications (33.4% vs. 33.6%, P = .92), compared with their non-CLL counterparts. However, the incidence of infection was comparable (8.5% vs. 9.4%, P = .38).
However, patients with CLL required blood transfusions more frequently (33.7% vs. 28.4%, P = .003) than did patients without CLL. In addition, patients with CLL were more likely to be readmitted within 90 days of discharge, compared with their counterparts, and “respiratory reasons, including pneumonia, contributed significantly to the readmission burden in this cohort,” the researchers, led by Josef Madrigal, BS, of the University of California, Los Angeles, stated.
“The inherent risk of transfusion and the possible benefits of blood conservation interventions must be considered in this patient population. Increased risk of rehospitalization in patients with CLL suggests the need for measures aimed at mitigating the risk of respiratory complications,” the researchers concluded.
There were no conflicts of interest reported in the article.
FROM THE ANNALS OF THORACIC SURGERY
Genetic shift increases susceptibility to childhood ALL
A genetically induced shift toward higher lymphocyte counts was found to increase susceptibility to childhood acute lymphoblastic leukemia, according to the results of a large genome-wide association study of 2,666 childhood patients with ALL as compared with 60,272 control individuals.
The development of ALL is thought to follow a two-hit model of leukemogenesis; in utero formation of a preleukemic clone and subsequent postnatal acquisition of secondary somatic mutations that leads to overt leukemia, according to Linda Kachuri, PhD, of the department of epidemiology and biostatistics, University of California, San Francisco, and colleagues.
The development of ALL is thought to follow a two-hit model of leukemogenesis; in utero formation of a preleukemic clone and subsequent postnatal acquisition of secondary somatic mutations that leads to overt leukemia, according to Linda Kachuri, PhD, of the Department of Epidemiology and Biostatistics, University of California San Francisco, and colleagues.
Previous research has shown that several childhood-ALL–risk regions have also been associated with variation in blood-cell traits and a recent phenome-wide association study of childhood ALL identified platelet count as the most enriched trait among known ALL-risk loci. To further explore this issue, the researchers conducted their comprehensive study of the role of blood-cell-trait variation in the etiology of childhood ALL.
The researchers identified 3,000 blood-cell-trait–associated variants, which accounted for 4.0% to 23.9% of trait variation and included 115 loci associated with blood-cell ratios: lymphocyte-to-monocyte ratio (LMR); neutrophil-to-lymphocyte ratio (NLR); and platelet-to-lymphocyte ratio (PLR), according to a report published online in The American Journal of Human Genetics.
Lymphocyte risk
The researchers found that ALL susceptibility was genetically correlated with lymphocyte counts (rg = 0.088, P = .0004) and PLR (rg = 0.072, P = .0017).
Using Mendelian randomization analyses, a genetically predicted increase in lymphocyte counts was found to be associated with increased ALL risk (odds ratio [OR] = 1.16, P = .031). This correlation was strengthened after the researchers accounted for other cell types (OR = 1.43, P = .0009).
The researchers observed positive associations with increasing LMR (OR = 1.22, P = .0017) as well as inverse effects for NLR (OR = 0.67, P = .0003) and PLR (OR = 0.80, P = .002).
“We identified the cell-type ratios LMR, NLR, and PLR as independent risk factors for ALL and found evidence that these ratios have distinct genetic mechanisms that are not captured by their component traits. In multivariable MR analyses that concurrently modeled the effects of lymphocyte, monocyte, neutrophil, and platelet counts on ALL, lymphocytes remained as the only independent risk factor and this association with ALL strengthened compared to univariate analyses,” the researchers stated.
They reported that they had no competing interests.
A genetically induced shift toward higher lymphocyte counts was found to increase susceptibility to childhood acute lymphoblastic leukemia, according to the results of a large genome-wide association study of 2,666 childhood patients with ALL as compared with 60,272 control individuals.
The development of ALL is thought to follow a two-hit model of leukemogenesis; in utero formation of a preleukemic clone and subsequent postnatal acquisition of secondary somatic mutations that leads to overt leukemia, according to Linda Kachuri, PhD, of the department of epidemiology and biostatistics, University of California, San Francisco, and colleagues.
The development of ALL is thought to follow a two-hit model of leukemogenesis; in utero formation of a preleukemic clone and subsequent postnatal acquisition of secondary somatic mutations that leads to overt leukemia, according to Linda Kachuri, PhD, of the Department of Epidemiology and Biostatistics, University of California San Francisco, and colleagues.
Previous research has shown that several childhood-ALL–risk regions have also been associated with variation in blood-cell traits and a recent phenome-wide association study of childhood ALL identified platelet count as the most enriched trait among known ALL-risk loci. To further explore this issue, the researchers conducted their comprehensive study of the role of blood-cell-trait variation in the etiology of childhood ALL.
The researchers identified 3,000 blood-cell-trait–associated variants, which accounted for 4.0% to 23.9% of trait variation and included 115 loci associated with blood-cell ratios: lymphocyte-to-monocyte ratio (LMR); neutrophil-to-lymphocyte ratio (NLR); and platelet-to-lymphocyte ratio (PLR), according to a report published online in The American Journal of Human Genetics.
Lymphocyte risk
The researchers found that ALL susceptibility was genetically correlated with lymphocyte counts (rg = 0.088, P = .0004) and PLR (rg = 0.072, P = .0017).
Using Mendelian randomization analyses, a genetically predicted increase in lymphocyte counts was found to be associated with increased ALL risk (odds ratio [OR] = 1.16, P = .031). This correlation was strengthened after the researchers accounted for other cell types (OR = 1.43, P = .0009).
The researchers observed positive associations with increasing LMR (OR = 1.22, P = .0017) as well as inverse effects for NLR (OR = 0.67, P = .0003) and PLR (OR = 0.80, P = .002).
“We identified the cell-type ratios LMR, NLR, and PLR as independent risk factors for ALL and found evidence that these ratios have distinct genetic mechanisms that are not captured by their component traits. In multivariable MR analyses that concurrently modeled the effects of lymphocyte, monocyte, neutrophil, and platelet counts on ALL, lymphocytes remained as the only independent risk factor and this association with ALL strengthened compared to univariate analyses,” the researchers stated.
They reported that they had no competing interests.
A genetically induced shift toward higher lymphocyte counts was found to increase susceptibility to childhood acute lymphoblastic leukemia, according to the results of a large genome-wide association study of 2,666 childhood patients with ALL as compared with 60,272 control individuals.
The development of ALL is thought to follow a two-hit model of leukemogenesis; in utero formation of a preleukemic clone and subsequent postnatal acquisition of secondary somatic mutations that leads to overt leukemia, according to Linda Kachuri, PhD, of the department of epidemiology and biostatistics, University of California, San Francisco, and colleagues.
The development of ALL is thought to follow a two-hit model of leukemogenesis; in utero formation of a preleukemic clone and subsequent postnatal acquisition of secondary somatic mutations that leads to overt leukemia, according to Linda Kachuri, PhD, of the Department of Epidemiology and Biostatistics, University of California San Francisco, and colleagues.
Previous research has shown that several childhood-ALL–risk regions have also been associated with variation in blood-cell traits and a recent phenome-wide association study of childhood ALL identified platelet count as the most enriched trait among known ALL-risk loci. To further explore this issue, the researchers conducted their comprehensive study of the role of blood-cell-trait variation in the etiology of childhood ALL.
The researchers identified 3,000 blood-cell-trait–associated variants, which accounted for 4.0% to 23.9% of trait variation and included 115 loci associated with blood-cell ratios: lymphocyte-to-monocyte ratio (LMR); neutrophil-to-lymphocyte ratio (NLR); and platelet-to-lymphocyte ratio (PLR), according to a report published online in The American Journal of Human Genetics.
Lymphocyte risk
The researchers found that ALL susceptibility was genetically correlated with lymphocyte counts (rg = 0.088, P = .0004) and PLR (rg = 0.072, P = .0017).
Using Mendelian randomization analyses, a genetically predicted increase in lymphocyte counts was found to be associated with increased ALL risk (odds ratio [OR] = 1.16, P = .031). This correlation was strengthened after the researchers accounted for other cell types (OR = 1.43, P = .0009).
The researchers observed positive associations with increasing LMR (OR = 1.22, P = .0017) as well as inverse effects for NLR (OR = 0.67, P = .0003) and PLR (OR = 0.80, P = .002).
“We identified the cell-type ratios LMR, NLR, and PLR as independent risk factors for ALL and found evidence that these ratios have distinct genetic mechanisms that are not captured by their component traits. In multivariable MR analyses that concurrently modeled the effects of lymphocyte, monocyte, neutrophil, and platelet counts on ALL, lymphocytes remained as the only independent risk factor and this association with ALL strengthened compared to univariate analyses,” the researchers stated.
They reported that they had no competing interests.
FROM THE AMERICAN JOURNAL OF HUMAN GENETICS
New treatments have transformed Ph+ acute lymphoblastic leukemia care
The use of novel, chemotherapy-free regimens in Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL) is poised to become the new standard of care, according to a review assessment by Nicholas Short, MD, of the University of Texas MD Anderson Cancer Center, Houston, and colleagues.
Since the introduction of highly potent BCR-ABL–mutation tyrosine kinase inhibitors (TKIs), Ph+ ALL in adults has been transformed from an historically poor prognosis disease to a relatively favorable–risk acute leukemia, according to their report published online in Clinical Lymphoma, Myeloma and Leukemia.
Dr. Short and colleagues reviewed the state of the art in Ph+ ALL care, comparing historically intensive with the more modern nonintensive treatments as part of the SOHO (Society of Hematologic Oncology) State of the Art Updates & Next Questions.
Treatment comparisons
Ph+ ALL outcomes have dramatically improved in the past 20 years, first with the addition of BCR-ABL TKIs to chemotherapy backbones and, more recently, with the development of more potent later-generation TKIs and the use of chemotherapy-free regimens.
Since the introduction of TKIs, most studies have evaluated them in combination with intensive chemotherapy such as hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone alternating with high-dose methotrexate and cytarabine) or similar regimens, according to Dr. Short and colleagues. However, the role of intensive chemotherapy in treating patients with Ph+ ALL has been increasingly questioned with the development of more active, broader spectrum TKIs such as ponatinib and effective novel monoclonal antibody constructs such as blinatumomab.
In particular, encouraging early results have been observed with blinatumomab-based, chemotherapy-free regimens, challenging previous notions that all patients with Ph+ ALL should undergo allogeneic hematopoietic stem cell transplantation (HSCT) in first remission, according to Dr. Short and colleagues. These regimens are capable of achieving deep and durable remissions without need for transplant in the vast majority of patients, particularly when combined with ponatinib.
“Given the multiple recent advances in the management of Ph+ ALL, we can reasonably envision a future in which what was once one of the most aggressive forms of leukemia is now considered nearly universally curable without either need for either chemotherapy or HSCT,” the authors concluded.
Disclosures for the authors were not reported in the review article.
The use of novel, chemotherapy-free regimens in Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL) is poised to become the new standard of care, according to a review assessment by Nicholas Short, MD, of the University of Texas MD Anderson Cancer Center, Houston, and colleagues.
Since the introduction of highly potent BCR-ABL–mutation tyrosine kinase inhibitors (TKIs), Ph+ ALL in adults has been transformed from an historically poor prognosis disease to a relatively favorable–risk acute leukemia, according to their report published online in Clinical Lymphoma, Myeloma and Leukemia.
Dr. Short and colleagues reviewed the state of the art in Ph+ ALL care, comparing historically intensive with the more modern nonintensive treatments as part of the SOHO (Society of Hematologic Oncology) State of the Art Updates & Next Questions.
Treatment comparisons
Ph+ ALL outcomes have dramatically improved in the past 20 years, first with the addition of BCR-ABL TKIs to chemotherapy backbones and, more recently, with the development of more potent later-generation TKIs and the use of chemotherapy-free regimens.
Since the introduction of TKIs, most studies have evaluated them in combination with intensive chemotherapy such as hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone alternating with high-dose methotrexate and cytarabine) or similar regimens, according to Dr. Short and colleagues. However, the role of intensive chemotherapy in treating patients with Ph+ ALL has been increasingly questioned with the development of more active, broader spectrum TKIs such as ponatinib and effective novel monoclonal antibody constructs such as blinatumomab.
In particular, encouraging early results have been observed with blinatumomab-based, chemotherapy-free regimens, challenging previous notions that all patients with Ph+ ALL should undergo allogeneic hematopoietic stem cell transplantation (HSCT) in first remission, according to Dr. Short and colleagues. These regimens are capable of achieving deep and durable remissions without need for transplant in the vast majority of patients, particularly when combined with ponatinib.
“Given the multiple recent advances in the management of Ph+ ALL, we can reasonably envision a future in which what was once one of the most aggressive forms of leukemia is now considered nearly universally curable without either need for either chemotherapy or HSCT,” the authors concluded.
Disclosures for the authors were not reported in the review article.
The use of novel, chemotherapy-free regimens in Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL) is poised to become the new standard of care, according to a review assessment by Nicholas Short, MD, of the University of Texas MD Anderson Cancer Center, Houston, and colleagues.
Since the introduction of highly potent BCR-ABL–mutation tyrosine kinase inhibitors (TKIs), Ph+ ALL in adults has been transformed from an historically poor prognosis disease to a relatively favorable–risk acute leukemia, according to their report published online in Clinical Lymphoma, Myeloma and Leukemia.
Dr. Short and colleagues reviewed the state of the art in Ph+ ALL care, comparing historically intensive with the more modern nonintensive treatments as part of the SOHO (Society of Hematologic Oncology) State of the Art Updates & Next Questions.
Treatment comparisons
Ph+ ALL outcomes have dramatically improved in the past 20 years, first with the addition of BCR-ABL TKIs to chemotherapy backbones and, more recently, with the development of more potent later-generation TKIs and the use of chemotherapy-free regimens.
Since the introduction of TKIs, most studies have evaluated them in combination with intensive chemotherapy such as hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone alternating with high-dose methotrexate and cytarabine) or similar regimens, according to Dr. Short and colleagues. However, the role of intensive chemotherapy in treating patients with Ph+ ALL has been increasingly questioned with the development of more active, broader spectrum TKIs such as ponatinib and effective novel monoclonal antibody constructs such as blinatumomab.
In particular, encouraging early results have been observed with blinatumomab-based, chemotherapy-free regimens, challenging previous notions that all patients with Ph+ ALL should undergo allogeneic hematopoietic stem cell transplantation (HSCT) in first remission, according to Dr. Short and colleagues. These regimens are capable of achieving deep and durable remissions without need for transplant in the vast majority of patients, particularly when combined with ponatinib.
“Given the multiple recent advances in the management of Ph+ ALL, we can reasonably envision a future in which what was once one of the most aggressive forms of leukemia is now considered nearly universally curable without either need for either chemotherapy or HSCT,” the authors concluded.
Disclosures for the authors were not reported in the review article.
FROM CLINICAL LYMPHOMA, MYELOMA AND LEUKEMIA
One in three cancer articles on social media has wrong info
Of the 200 most popular articles (50 each for prostate, lung, breast, and colorectal cancer), about a third (32.5%, n = 65) contained misinformation.
Among these articles containing misinformation, 76.9% (50/65) contained harmful information.
“The Internet is a leading source of health misinformation,” the study authors wrote. This is “particularly true for social media, where false information spreads faster and more broadly than fact-checked information,” they said, citing other research.
“We need to address these issues head on,” said lead author Skyler Johnson, MD, of the University of Utah’s Huntsman Cancer Institute in Salt Lake City.
“As a medical community, we can’t ignore the problem of cancer misinformation on social media or ask our patients to ignore it. We must empathize with our patients and help them when they encounter this type of information,” he said in a statement. “My goal is to help answer their questions, and provide cancer patients with accurate information that will give them the best chance for the best outcome.”
The study was published online July 22 in the Journal of the National Cancer Institute.
The study period ran from 2018 to 2019, and looked at articles posted on social media platforms Facebook, Reddit, Twitter, or Pinterest. Popularity was measured by engagement with readers, such as upvotes, comments, reactions, and shares.
Some of the articles came from long-established news entities such as CBS News, The New York Times, and medical journals, while others came from fleeting crowdfunding web pages and fledging nontraditional news sites.
One example of popular and harmful misinformation highlighted by Dr. Johnson in an interview was titled, “44-Year-Old Mother Claims CBD Oil Cured Her of Breast Cancer within 5 Months.” Posted on truththeory.com in February 2018, the article is tagged as “opinion” by the publisher and in turn links to another news story about the same woman in the UK’s Daily Mail newspaper.
The ideas and claims in such articles can be very influential, Jennifer L. Lycette, MD, suggested in a recent blog post.
“After 18 years as a cancer doctor, it sadly doesn’t come as a surprise anymore when a patient declines treatment recommendations and instead opts for ‘alternative’ treatment,” she wrote.
Sometimes, misinformation is not sensational but is still effective via clever wording and presentation, observed Brian G. Southwell, PhD, of Duke University, Durham, N.C., who has studied patients and misinformation.
“It isn’t the falsehood that is somehow magically attractive, per se, but the way that misinformation is often framed that can make it attractive,” he said in an interview.
Dr. Southwell recommends that clinicians be proactive about medical misinformation.
“Rather than expect patients to raise concerns without prompting, health care providers should invite conversations about potential misinformation with their patients,” he wrote in a recent essay in the American Journal of Public Health.
In short, ask patients what they know about the treatment of their cancer, he suggests.
“Patients don’t typically know that the misinformation they are encountering is misinformation,” said Dr. Southwell. “Approaching patients with compassion and empathy is a good first step.”
Study details
For the study, reported by Johnson et al., two National Comprehensive Cancer Network panel members were selected as content experts for each of the four cancers and were tasked with reviewing the primary medical claims in each article. The experts then completed a set of ratings to arrive at the proportion of misinformation and potential for harm in each article.
Of the 200 articles, 41.5% were from nontraditional news (digital only), 37.5% were from traditional news sources (online versions of print and/or broadcast media), 17% were from medical journals, 3% were from a crowdfunding site, and 1% were from personal blogs.
This expert review concluded that nearly one-third of the articles contained misinformation, as noted above. The misinformation was described as misleading (title not supported by text or statistics/data do not support conclusion, 28.8%), strength of the evidence mischaracterized (weak evidence portrayed as strong or vice versa, 27.7%) and unproven therapies (not studied or insufficient evidence, 26.7%).
Notably, the median number of engagements, such as likes on Twitter, for articles with misinformation was greater than that of factual articles (median, 2,300 vs. 1,600; P = .05).
In total, 30.5% of all 200 articles contained harmful information. This was described as harmful inaction (could lead to delay or not seeking medical attention for treatable/curable condition, 31.0%), economic harm (out-of-pocket financial costs associated with treatment/travel, 27.7%), harmful action (potentially toxic effects of the suggested test/treatment, 17.0%), and harmful interactions (known/unknown medical interactions with curative therapies, 16.2%).
The median number of engagements for articles with harmful information was statistically significantly greater than that of articles with correct information (median, 2,300 vs. 1,500; P = .007).
A limitation of the study is that it included only the most popular English language cancer articles.
This study was funded in part by the Huntsman Cancer Institute. Dr. Johnson, Dr. Lycette, and Dr. Southwell have disclosed no relevant financial relationships. Some study authors have ties to the pharmaceutical industry.
A version of this article first appeared on Medscape.com.
Of the 200 most popular articles (50 each for prostate, lung, breast, and colorectal cancer), about a third (32.5%, n = 65) contained misinformation.
Among these articles containing misinformation, 76.9% (50/65) contained harmful information.
“The Internet is a leading source of health misinformation,” the study authors wrote. This is “particularly true for social media, where false information spreads faster and more broadly than fact-checked information,” they said, citing other research.
“We need to address these issues head on,” said lead author Skyler Johnson, MD, of the University of Utah’s Huntsman Cancer Institute in Salt Lake City.
“As a medical community, we can’t ignore the problem of cancer misinformation on social media or ask our patients to ignore it. We must empathize with our patients and help them when they encounter this type of information,” he said in a statement. “My goal is to help answer their questions, and provide cancer patients with accurate information that will give them the best chance for the best outcome.”
The study was published online July 22 in the Journal of the National Cancer Institute.
The study period ran from 2018 to 2019, and looked at articles posted on social media platforms Facebook, Reddit, Twitter, or Pinterest. Popularity was measured by engagement with readers, such as upvotes, comments, reactions, and shares.
Some of the articles came from long-established news entities such as CBS News, The New York Times, and medical journals, while others came from fleeting crowdfunding web pages and fledging nontraditional news sites.
One example of popular and harmful misinformation highlighted by Dr. Johnson in an interview was titled, “44-Year-Old Mother Claims CBD Oil Cured Her of Breast Cancer within 5 Months.” Posted on truththeory.com in February 2018, the article is tagged as “opinion” by the publisher and in turn links to another news story about the same woman in the UK’s Daily Mail newspaper.
The ideas and claims in such articles can be very influential, Jennifer L. Lycette, MD, suggested in a recent blog post.
“After 18 years as a cancer doctor, it sadly doesn’t come as a surprise anymore when a patient declines treatment recommendations and instead opts for ‘alternative’ treatment,” she wrote.
Sometimes, misinformation is not sensational but is still effective via clever wording and presentation, observed Brian G. Southwell, PhD, of Duke University, Durham, N.C., who has studied patients and misinformation.
“It isn’t the falsehood that is somehow magically attractive, per se, but the way that misinformation is often framed that can make it attractive,” he said in an interview.
Dr. Southwell recommends that clinicians be proactive about medical misinformation.
“Rather than expect patients to raise concerns without prompting, health care providers should invite conversations about potential misinformation with their patients,” he wrote in a recent essay in the American Journal of Public Health.
In short, ask patients what they know about the treatment of their cancer, he suggests.
“Patients don’t typically know that the misinformation they are encountering is misinformation,” said Dr. Southwell. “Approaching patients with compassion and empathy is a good first step.”
Study details
For the study, reported by Johnson et al., two National Comprehensive Cancer Network panel members were selected as content experts for each of the four cancers and were tasked with reviewing the primary medical claims in each article. The experts then completed a set of ratings to arrive at the proportion of misinformation and potential for harm in each article.
Of the 200 articles, 41.5% were from nontraditional news (digital only), 37.5% were from traditional news sources (online versions of print and/or broadcast media), 17% were from medical journals, 3% were from a crowdfunding site, and 1% were from personal blogs.
This expert review concluded that nearly one-third of the articles contained misinformation, as noted above. The misinformation was described as misleading (title not supported by text or statistics/data do not support conclusion, 28.8%), strength of the evidence mischaracterized (weak evidence portrayed as strong or vice versa, 27.7%) and unproven therapies (not studied or insufficient evidence, 26.7%).
Notably, the median number of engagements, such as likes on Twitter, for articles with misinformation was greater than that of factual articles (median, 2,300 vs. 1,600; P = .05).
In total, 30.5% of all 200 articles contained harmful information. This was described as harmful inaction (could lead to delay or not seeking medical attention for treatable/curable condition, 31.0%), economic harm (out-of-pocket financial costs associated with treatment/travel, 27.7%), harmful action (potentially toxic effects of the suggested test/treatment, 17.0%), and harmful interactions (known/unknown medical interactions with curative therapies, 16.2%).
The median number of engagements for articles with harmful information was statistically significantly greater than that of articles with correct information (median, 2,300 vs. 1,500; P = .007).
A limitation of the study is that it included only the most popular English language cancer articles.
This study was funded in part by the Huntsman Cancer Institute. Dr. Johnson, Dr. Lycette, and Dr. Southwell have disclosed no relevant financial relationships. Some study authors have ties to the pharmaceutical industry.
A version of this article first appeared on Medscape.com.
Of the 200 most popular articles (50 each for prostate, lung, breast, and colorectal cancer), about a third (32.5%, n = 65) contained misinformation.
Among these articles containing misinformation, 76.9% (50/65) contained harmful information.
“The Internet is a leading source of health misinformation,” the study authors wrote. This is “particularly true for social media, where false information spreads faster and more broadly than fact-checked information,” they said, citing other research.
“We need to address these issues head on,” said lead author Skyler Johnson, MD, of the University of Utah’s Huntsman Cancer Institute in Salt Lake City.
“As a medical community, we can’t ignore the problem of cancer misinformation on social media or ask our patients to ignore it. We must empathize with our patients and help them when they encounter this type of information,” he said in a statement. “My goal is to help answer their questions, and provide cancer patients with accurate information that will give them the best chance for the best outcome.”
The study was published online July 22 in the Journal of the National Cancer Institute.
The study period ran from 2018 to 2019, and looked at articles posted on social media platforms Facebook, Reddit, Twitter, or Pinterest. Popularity was measured by engagement with readers, such as upvotes, comments, reactions, and shares.
Some of the articles came from long-established news entities such as CBS News, The New York Times, and medical journals, while others came from fleeting crowdfunding web pages and fledging nontraditional news sites.
One example of popular and harmful misinformation highlighted by Dr. Johnson in an interview was titled, “44-Year-Old Mother Claims CBD Oil Cured Her of Breast Cancer within 5 Months.” Posted on truththeory.com in February 2018, the article is tagged as “opinion” by the publisher and in turn links to another news story about the same woman in the UK’s Daily Mail newspaper.
The ideas and claims in such articles can be very influential, Jennifer L. Lycette, MD, suggested in a recent blog post.
“After 18 years as a cancer doctor, it sadly doesn’t come as a surprise anymore when a patient declines treatment recommendations and instead opts for ‘alternative’ treatment,” she wrote.
Sometimes, misinformation is not sensational but is still effective via clever wording and presentation, observed Brian G. Southwell, PhD, of Duke University, Durham, N.C., who has studied patients and misinformation.
“It isn’t the falsehood that is somehow magically attractive, per se, but the way that misinformation is often framed that can make it attractive,” he said in an interview.
Dr. Southwell recommends that clinicians be proactive about medical misinformation.
“Rather than expect patients to raise concerns without prompting, health care providers should invite conversations about potential misinformation with their patients,” he wrote in a recent essay in the American Journal of Public Health.
In short, ask patients what they know about the treatment of their cancer, he suggests.
“Patients don’t typically know that the misinformation they are encountering is misinformation,” said Dr. Southwell. “Approaching patients with compassion and empathy is a good first step.”
Study details
For the study, reported by Johnson et al., two National Comprehensive Cancer Network panel members were selected as content experts for each of the four cancers and were tasked with reviewing the primary medical claims in each article. The experts then completed a set of ratings to arrive at the proportion of misinformation and potential for harm in each article.
Of the 200 articles, 41.5% were from nontraditional news (digital only), 37.5% were from traditional news sources (online versions of print and/or broadcast media), 17% were from medical journals, 3% were from a crowdfunding site, and 1% were from personal blogs.
This expert review concluded that nearly one-third of the articles contained misinformation, as noted above. The misinformation was described as misleading (title not supported by text or statistics/data do not support conclusion, 28.8%), strength of the evidence mischaracterized (weak evidence portrayed as strong or vice versa, 27.7%) and unproven therapies (not studied or insufficient evidence, 26.7%).
Notably, the median number of engagements, such as likes on Twitter, for articles with misinformation was greater than that of factual articles (median, 2,300 vs. 1,600; P = .05).
In total, 30.5% of all 200 articles contained harmful information. This was described as harmful inaction (could lead to delay or not seeking medical attention for treatable/curable condition, 31.0%), economic harm (out-of-pocket financial costs associated with treatment/travel, 27.7%), harmful action (potentially toxic effects of the suggested test/treatment, 17.0%), and harmful interactions (known/unknown medical interactions with curative therapies, 16.2%).
The median number of engagements for articles with harmful information was statistically significantly greater than that of articles with correct information (median, 2,300 vs. 1,500; P = .007).
A limitation of the study is that it included only the most popular English language cancer articles.
This study was funded in part by the Huntsman Cancer Institute. Dr. Johnson, Dr. Lycette, and Dr. Southwell have disclosed no relevant financial relationships. Some study authors have ties to the pharmaceutical industry.
A version of this article first appeared on Medscape.com.
Targeted CLL treatments found effective in managing associated autoimmune cytopenias
Newer targeted drugs for chronic lymphocytic leukemia also appear to have a beneficial impact on underlying autoimmune cytopenias (AICs), results of a large retrospective study suggest.
Many autoimmune cytopenias improved or resolved during treatment with ibrutinib, idelalisib, or venetoclax, according to authors of the study, which appears in the journal Blood.
Treatment-emergent autoimmune cytopenias were seen in a “negligible portion” of patients overall, according to the report. The prevalence was about 1% each for patients treated with ibrutinib or idelalisib, though seen more frequently (at 7%) among patients who received venetoclax.
Nevertheless, treatment-emergent autoimmune cytopenias were “easily manageable” without interventions such as steroids and rituximab, and without need to interrupt the targeted treatment for chronic lymphocytic leukemia (CLL), according to the authors, led by Candida Vitale, MD, PhD, of the department of molecular biotechnology and health sciences at the University of Torino in Italy.
“Ibrutinib, idelalisib, and venetoclax have a beneficial impact on CLL-related preexisting AICs, achieving in most patients, in parallel with the consolidated antitumor efficacy, an effective control of the autoimmune phenomena,” Dr. Vitale and coauthors wrote in their report.
Study results
The retrospective study included 815 patients, of whom 572 were treated with ibrutinib, 143 with idelalisib plus rituximab, and 100 with venetoclax. Nine percent of ibrutinib-treated patients and 12% of venetoclax-treated patients also received an anti-CD20 monoclonal antibody, rituximab or obinutuzumab.
One hundred and four patients (13%) had preexisting autoimmune cytopenias, though the majority were resolved or controlled at the time targeted therapy was started.
Of patients with autoimmune cytopenias that were unresolved at the beginning of targeted therapy, 80% improved or resolved after starting targeted treatment, authors reported.
Most patients who developed autoimmune cytopenias on treatment had high-risk features such as unmutated IGHV, del(17)p, or TP53 mutation, according to the report.
Those treatment-emergent autoimmune cytopenias were seen in 1% of the ibrutinib group, 0.9% of the idelalisib group, and 7% of the venetoclax group. Out of 12 total treatment-emergent autoimmune cytopenias, all but 2 were resolved or controlled with dose reductions or temporary suspensions and use of steroids or rituximab, the report shows.
The higher incidence of autoimmune cytopenias in the venetoclax group held steady even when considering just the patients who had relapsed/refractory disease or had at least two prior lines of therapy, suggesting a “more meaningful” incidence, compared to what was observed for ibrutinib and idelalisib, the investigators said.
“However, the risk of autoimmune cytopenia episodes should not limit the use of venetoclax, considering the strong efficacy of this drug in treating patients with CLL, including those with high-risk features, and the possibility of effectively managing autoimmune complications, mostly without treatment interruption,” they concluded in their report.
Implications for patients with CLL
Findings of this study indicate that targeted therapies are effective for managing both CLL and autoimmune cytopenias, according to Carol Moreno, MD, PhD, of Hospital Sant Pau in Barcelona.
Moreover, the targeted therapies do not appear to change the overall prevalence of autoimmune cytopenias, compared to untreated patients, Dr. Moreno said in a commentary on the findings also published in Blood.
“These results are consistent with the concept that targeted therapies are not associated with a higher risk of autoimmune cytopenias, and that, if present, can be managed with immunosuppressive agents,” she wrote.
Autoimmune cytopenias and CLL
Autoimmune cytopenias are a relatively common complication of CLL, occurring in 5%-9% of CLL patients, Dr. Vitale and coauthors said in their report. The most common presentations include autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP).
Evidence from earlier studies suggests that treatment for CLL may trigger autoimmune cytopenias. Results of retrospective studies in the 1990s linked single-agent fludarabine to increased risk of AIHA, Dr. Moreno said in the commentary.
However, subsequent studies showed that fludarabine plus cyclophosphamide (FC) and fludarabine, cyclophosphamide, and rituximab (FCR) were associated with low proportions of AIHA.
“Taken together, these results convincingly suggest that rather than treatment, it is the lack of response to it that conveys a higher risk of AIC,” Dr. Moreno wrote.
Management considerations
There are currently no clinical practice guidelines that advise on how to manage patients who develop AICs during targeted treatment for CLL, Dr. Vitale and colleagues said in their report.
However, this new study data may help inform management of patients with CLL and an autoimmune cytopenia, Dr. Moreno said in the commentary.
If the patient doesn’t immediately require CLL treatment, patients can be managed according to existing guidelines for AIHA and ITP, she said. “Nonresponding patients should be given CLL therapy,” she added.
For CLL patients who do require therapy and have a preexisting or treatment-emergent AIC, a “CLL-oriented” treatment approach could be considered, according to Dr. Moreno.
“A reasonable approach consists of a short course (2 to 4 weeks) of corticosteroids followed by effective CLL therapy (i.e., FCR, bendamustine plus rituximab or ibrutinib), depending on the clinical situation,” she added.
Dr. Vitale reported receiving consultancy fees from Janssen outside the submitted work. Dr. Moreno declared no competing financial interests related to her commentary.
Newer targeted drugs for chronic lymphocytic leukemia also appear to have a beneficial impact on underlying autoimmune cytopenias (AICs), results of a large retrospective study suggest.
Many autoimmune cytopenias improved or resolved during treatment with ibrutinib, idelalisib, or venetoclax, according to authors of the study, which appears in the journal Blood.
Treatment-emergent autoimmune cytopenias were seen in a “negligible portion” of patients overall, according to the report. The prevalence was about 1% each for patients treated with ibrutinib or idelalisib, though seen more frequently (at 7%) among patients who received venetoclax.
Nevertheless, treatment-emergent autoimmune cytopenias were “easily manageable” without interventions such as steroids and rituximab, and without need to interrupt the targeted treatment for chronic lymphocytic leukemia (CLL), according to the authors, led by Candida Vitale, MD, PhD, of the department of molecular biotechnology and health sciences at the University of Torino in Italy.
“Ibrutinib, idelalisib, and venetoclax have a beneficial impact on CLL-related preexisting AICs, achieving in most patients, in parallel with the consolidated antitumor efficacy, an effective control of the autoimmune phenomena,” Dr. Vitale and coauthors wrote in their report.
Study results
The retrospective study included 815 patients, of whom 572 were treated with ibrutinib, 143 with idelalisib plus rituximab, and 100 with venetoclax. Nine percent of ibrutinib-treated patients and 12% of venetoclax-treated patients also received an anti-CD20 monoclonal antibody, rituximab or obinutuzumab.
One hundred and four patients (13%) had preexisting autoimmune cytopenias, though the majority were resolved or controlled at the time targeted therapy was started.
Of patients with autoimmune cytopenias that were unresolved at the beginning of targeted therapy, 80% improved or resolved after starting targeted treatment, authors reported.
Most patients who developed autoimmune cytopenias on treatment had high-risk features such as unmutated IGHV, del(17)p, or TP53 mutation, according to the report.
Those treatment-emergent autoimmune cytopenias were seen in 1% of the ibrutinib group, 0.9% of the idelalisib group, and 7% of the venetoclax group. Out of 12 total treatment-emergent autoimmune cytopenias, all but 2 were resolved or controlled with dose reductions or temporary suspensions and use of steroids or rituximab, the report shows.
The higher incidence of autoimmune cytopenias in the venetoclax group held steady even when considering just the patients who had relapsed/refractory disease or had at least two prior lines of therapy, suggesting a “more meaningful” incidence, compared to what was observed for ibrutinib and idelalisib, the investigators said.
“However, the risk of autoimmune cytopenia episodes should not limit the use of venetoclax, considering the strong efficacy of this drug in treating patients with CLL, including those with high-risk features, and the possibility of effectively managing autoimmune complications, mostly without treatment interruption,” they concluded in their report.
Implications for patients with CLL
Findings of this study indicate that targeted therapies are effective for managing both CLL and autoimmune cytopenias, according to Carol Moreno, MD, PhD, of Hospital Sant Pau in Barcelona.
Moreover, the targeted therapies do not appear to change the overall prevalence of autoimmune cytopenias, compared to untreated patients, Dr. Moreno said in a commentary on the findings also published in Blood.
“These results are consistent with the concept that targeted therapies are not associated with a higher risk of autoimmune cytopenias, and that, if present, can be managed with immunosuppressive agents,” she wrote.
Autoimmune cytopenias and CLL
Autoimmune cytopenias are a relatively common complication of CLL, occurring in 5%-9% of CLL patients, Dr. Vitale and coauthors said in their report. The most common presentations include autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP).
Evidence from earlier studies suggests that treatment for CLL may trigger autoimmune cytopenias. Results of retrospective studies in the 1990s linked single-agent fludarabine to increased risk of AIHA, Dr. Moreno said in the commentary.
However, subsequent studies showed that fludarabine plus cyclophosphamide (FC) and fludarabine, cyclophosphamide, and rituximab (FCR) were associated with low proportions of AIHA.
“Taken together, these results convincingly suggest that rather than treatment, it is the lack of response to it that conveys a higher risk of AIC,” Dr. Moreno wrote.
Management considerations
There are currently no clinical practice guidelines that advise on how to manage patients who develop AICs during targeted treatment for CLL, Dr. Vitale and colleagues said in their report.
However, this new study data may help inform management of patients with CLL and an autoimmune cytopenia, Dr. Moreno said in the commentary.
If the patient doesn’t immediately require CLL treatment, patients can be managed according to existing guidelines for AIHA and ITP, she said. “Nonresponding patients should be given CLL therapy,” she added.
For CLL patients who do require therapy and have a preexisting or treatment-emergent AIC, a “CLL-oriented” treatment approach could be considered, according to Dr. Moreno.
“A reasonable approach consists of a short course (2 to 4 weeks) of corticosteroids followed by effective CLL therapy (i.e., FCR, bendamustine plus rituximab or ibrutinib), depending on the clinical situation,” she added.
Dr. Vitale reported receiving consultancy fees from Janssen outside the submitted work. Dr. Moreno declared no competing financial interests related to her commentary.
Newer targeted drugs for chronic lymphocytic leukemia also appear to have a beneficial impact on underlying autoimmune cytopenias (AICs), results of a large retrospective study suggest.
Many autoimmune cytopenias improved or resolved during treatment with ibrutinib, idelalisib, or venetoclax, according to authors of the study, which appears in the journal Blood.
Treatment-emergent autoimmune cytopenias were seen in a “negligible portion” of patients overall, according to the report. The prevalence was about 1% each for patients treated with ibrutinib or idelalisib, though seen more frequently (at 7%) among patients who received venetoclax.
Nevertheless, treatment-emergent autoimmune cytopenias were “easily manageable” without interventions such as steroids and rituximab, and without need to interrupt the targeted treatment for chronic lymphocytic leukemia (CLL), according to the authors, led by Candida Vitale, MD, PhD, of the department of molecular biotechnology and health sciences at the University of Torino in Italy.
“Ibrutinib, idelalisib, and venetoclax have a beneficial impact on CLL-related preexisting AICs, achieving in most patients, in parallel with the consolidated antitumor efficacy, an effective control of the autoimmune phenomena,” Dr. Vitale and coauthors wrote in their report.
Study results
The retrospective study included 815 patients, of whom 572 were treated with ibrutinib, 143 with idelalisib plus rituximab, and 100 with venetoclax. Nine percent of ibrutinib-treated patients and 12% of venetoclax-treated patients also received an anti-CD20 monoclonal antibody, rituximab or obinutuzumab.
One hundred and four patients (13%) had preexisting autoimmune cytopenias, though the majority were resolved or controlled at the time targeted therapy was started.
Of patients with autoimmune cytopenias that were unresolved at the beginning of targeted therapy, 80% improved or resolved after starting targeted treatment, authors reported.
Most patients who developed autoimmune cytopenias on treatment had high-risk features such as unmutated IGHV, del(17)p, or TP53 mutation, according to the report.
Those treatment-emergent autoimmune cytopenias were seen in 1% of the ibrutinib group, 0.9% of the idelalisib group, and 7% of the venetoclax group. Out of 12 total treatment-emergent autoimmune cytopenias, all but 2 were resolved or controlled with dose reductions or temporary suspensions and use of steroids or rituximab, the report shows.
The higher incidence of autoimmune cytopenias in the venetoclax group held steady even when considering just the patients who had relapsed/refractory disease or had at least two prior lines of therapy, suggesting a “more meaningful” incidence, compared to what was observed for ibrutinib and idelalisib, the investigators said.
“However, the risk of autoimmune cytopenia episodes should not limit the use of venetoclax, considering the strong efficacy of this drug in treating patients with CLL, including those with high-risk features, and the possibility of effectively managing autoimmune complications, mostly without treatment interruption,” they concluded in their report.
Implications for patients with CLL
Findings of this study indicate that targeted therapies are effective for managing both CLL and autoimmune cytopenias, according to Carol Moreno, MD, PhD, of Hospital Sant Pau in Barcelona.
Moreover, the targeted therapies do not appear to change the overall prevalence of autoimmune cytopenias, compared to untreated patients, Dr. Moreno said in a commentary on the findings also published in Blood.
“These results are consistent with the concept that targeted therapies are not associated with a higher risk of autoimmune cytopenias, and that, if present, can be managed with immunosuppressive agents,” she wrote.
Autoimmune cytopenias and CLL
Autoimmune cytopenias are a relatively common complication of CLL, occurring in 5%-9% of CLL patients, Dr. Vitale and coauthors said in their report. The most common presentations include autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP).
Evidence from earlier studies suggests that treatment for CLL may trigger autoimmune cytopenias. Results of retrospective studies in the 1990s linked single-agent fludarabine to increased risk of AIHA, Dr. Moreno said in the commentary.
However, subsequent studies showed that fludarabine plus cyclophosphamide (FC) and fludarabine, cyclophosphamide, and rituximab (FCR) were associated with low proportions of AIHA.
“Taken together, these results convincingly suggest that rather than treatment, it is the lack of response to it that conveys a higher risk of AIC,” Dr. Moreno wrote.
Management considerations
There are currently no clinical practice guidelines that advise on how to manage patients who develop AICs during targeted treatment for CLL, Dr. Vitale and colleagues said in their report.
However, this new study data may help inform management of patients with CLL and an autoimmune cytopenia, Dr. Moreno said in the commentary.
If the patient doesn’t immediately require CLL treatment, patients can be managed according to existing guidelines for AIHA and ITP, she said. “Nonresponding patients should be given CLL therapy,” she added.
For CLL patients who do require therapy and have a preexisting or treatment-emergent AIC, a “CLL-oriented” treatment approach could be considered, according to Dr. Moreno.
“A reasonable approach consists of a short course (2 to 4 weeks) of corticosteroids followed by effective CLL therapy (i.e., FCR, bendamustine plus rituximab or ibrutinib), depending on the clinical situation,” she added.
Dr. Vitale reported receiving consultancy fees from Janssen outside the submitted work. Dr. Moreno declared no competing financial interests related to her commentary.
FROM BLOOD
Leukemia highlights from ASCO 2021
Dr. Michael Grunwald presents highlights in the latest studies involving several types of leukemia from the ASCO 2021 Virtual Congress.
In a dose-optimization study of ponatinib, patients with chronic-phase chronic myeloid leukemia were randomized 1:1:1 to receive 45, 30, or 15 mg daily, with dose reductions occurring once patients met the primary endpoint of ≤1% BCR-ABL1. At 12 months, response rate was highest with the 45 mg to 15 mg regimen, and 73.3% of patients in this cohort maintained response.
The phase 1/2 ZUMA-3 study evaluated KTE-X19 in adults with relapsed/refractory B-cell acute lymphoblastic leukemia. The drug’s efficacy, speed of manufacture, and ease of safety management were found to be sufficient to provide long-term clinical benefit.
Another study focused on the efficacy and safety of aspacytarabine (BST-236) for patients with acute myeloid leukemia (AML) who were unfit for chemotherapy. The rate of complete remission was 39% among the AML population, and 63% of the population in complete remission had minimal residual disease.
Dr. Grunwald closes with a study of ponatinib and blinatumomab in patients with Philadelphia chromosome–positive acute lymphoblastic leukemia. The combination of both drugs was proven to be a safe and effective chemotherapy-free regimen in both newly diagnosed patients and patients with relapsed/refractory disease.
--
Michael R. Grunwald, MD, Chief, Leukemia Division. Department of Hematologic Oncology and Blood Disorders. Levine Cancer Institute, Atrium Health. Charlotte, North Carolina.
Michael R. Grunwald, MD, has disclosed the following relevant financial relationships:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AbbVie; Agios; Amgen; Astellas Pharma; Blueprint Medicines; Bristol Myers Squibb; Cardinal Health; Daiichi Sankyo; Gilead Sciences; Incyte; Karius; Pfizer; Premier Pharmaceuticals; Sierra Oncology; Stemline Therapeutics.
Received research grant from: Incyte; Janssen.
Dr. Michael Grunwald presents highlights in the latest studies involving several types of leukemia from the ASCO 2021 Virtual Congress.
In a dose-optimization study of ponatinib, patients with chronic-phase chronic myeloid leukemia were randomized 1:1:1 to receive 45, 30, or 15 mg daily, with dose reductions occurring once patients met the primary endpoint of ≤1% BCR-ABL1. At 12 months, response rate was highest with the 45 mg to 15 mg regimen, and 73.3% of patients in this cohort maintained response.
The phase 1/2 ZUMA-3 study evaluated KTE-X19 in adults with relapsed/refractory B-cell acute lymphoblastic leukemia. The drug’s efficacy, speed of manufacture, and ease of safety management were found to be sufficient to provide long-term clinical benefit.
Another study focused on the efficacy and safety of aspacytarabine (BST-236) for patients with acute myeloid leukemia (AML) who were unfit for chemotherapy. The rate of complete remission was 39% among the AML population, and 63% of the population in complete remission had minimal residual disease.
Dr. Grunwald closes with a study of ponatinib and blinatumomab in patients with Philadelphia chromosome–positive acute lymphoblastic leukemia. The combination of both drugs was proven to be a safe and effective chemotherapy-free regimen in both newly diagnosed patients and patients with relapsed/refractory disease.
--
Michael R. Grunwald, MD, Chief, Leukemia Division. Department of Hematologic Oncology and Blood Disorders. Levine Cancer Institute, Atrium Health. Charlotte, North Carolina.
Michael R. Grunwald, MD, has disclosed the following relevant financial relationships:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AbbVie; Agios; Amgen; Astellas Pharma; Blueprint Medicines; Bristol Myers Squibb; Cardinal Health; Daiichi Sankyo; Gilead Sciences; Incyte; Karius; Pfizer; Premier Pharmaceuticals; Sierra Oncology; Stemline Therapeutics.
Received research grant from: Incyte; Janssen.
Dr. Michael Grunwald presents highlights in the latest studies involving several types of leukemia from the ASCO 2021 Virtual Congress.
In a dose-optimization study of ponatinib, patients with chronic-phase chronic myeloid leukemia were randomized 1:1:1 to receive 45, 30, or 15 mg daily, with dose reductions occurring once patients met the primary endpoint of ≤1% BCR-ABL1. At 12 months, response rate was highest with the 45 mg to 15 mg regimen, and 73.3% of patients in this cohort maintained response.
The phase 1/2 ZUMA-3 study evaluated KTE-X19 in adults with relapsed/refractory B-cell acute lymphoblastic leukemia. The drug’s efficacy, speed of manufacture, and ease of safety management were found to be sufficient to provide long-term clinical benefit.
Another study focused on the efficacy and safety of aspacytarabine (BST-236) for patients with acute myeloid leukemia (AML) who were unfit for chemotherapy. The rate of complete remission was 39% among the AML population, and 63% of the population in complete remission had minimal residual disease.
Dr. Grunwald closes with a study of ponatinib and blinatumomab in patients with Philadelphia chromosome–positive acute lymphoblastic leukemia. The combination of both drugs was proven to be a safe and effective chemotherapy-free regimen in both newly diagnosed patients and patients with relapsed/refractory disease.
--
Michael R. Grunwald, MD, Chief, Leukemia Division. Department of Hematologic Oncology and Blood Disorders. Levine Cancer Institute, Atrium Health. Charlotte, North Carolina.
Michael R. Grunwald, MD, has disclosed the following relevant financial relationships:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AbbVie; Agios; Amgen; Astellas Pharma; Blueprint Medicines; Bristol Myers Squibb; Cardinal Health; Daiichi Sankyo; Gilead Sciences; Incyte; Karius; Pfizer; Premier Pharmaceuticals; Sierra Oncology; Stemline Therapeutics.
Received research grant from: Incyte; Janssen.
Ponatinib/blinatumomab start strong against Ph+ALL
For adults with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ALL), frontline therapy with the chemotherapy-free combination of ponatinib (Iclusig) and blinatumomab (Blincyto) shows promise as an alternative to early hematopoietic stem cell transplantation (HSCT), investigators in a single-arm phase 2 study reported.
In an interim analysis of the combination in patients with newly diagnosed or relapsed/refractory Ph+ALL or lymphoid accelerated or blast phase chronic myeloid leukemia (CML), 20 patients who received it as frontline therapy had a rate of complete responses (CR) or complete responses with partial recovery of blood counts (CRp) of 100% and a complete molecular remission (CMR) rate of 85%, reported Nicholas Short, MD, of the University of Texas MD Anderson Cancer Center in Houston.
“This translated into an estimated 2-year overall survival of 93%, with no patients undergoing transplant in first remission, and none having relapse at last follow-up,” he said in an oral abstract presented during the European Hematology Association annual congress.
Among patients with relapsed/refractory Ph+ALL, the CR/CRp rate was 89%, the CMR rate was 88%, and the estimated 2-year overall survival rate was 53%, he said.
Transplants on hold
“The big selling point is the ability to avoid stem cell transplant, which is not always the first thing you do in Ph-positive ALL, but it’s always on your mind,” said Gwen Nichols, MD, chief medical officer of the Leukemia and Lymphoma Society, who was not involved in the study.
“It looks, albeit with very limited follow-up, that patients haven’t relapsed yet such that transplant would be necessary. Anything we can do to avoid people having long-term complications that go along with an allogeneic transplant is a step in the right direction,” she said in an interview.
One combination, three cohorts
Ph+ALL comprises about 25% of all adult ALL. The standard of care in newly diagnosed patients is chemotherapy plus a tyrosine kinase inhibitor (TKI) targeted against the BCR-ABL transcript.
Ponatinib is a pan-BCR-ABL TKI that has been shown to have activity against ALL with T315I mutations, which are present in about 75% of the cases of relapsed disease, Dr. Short said.
Blinatumomab is a bi-specific T-cell engager (BiTe) that has been shown to be effective as monotherapy against relapsed/refractory Ph+ALL as monotherapy and in combination with dasatinib.
Dr. Short and colleagues enrolled patients with newly diagnosed or relapsed/refractory Ph+ALL or lymphoid accelerated or blast phase CML. Patients in the frontline cohort could have received one or two prior lines of chemotherapy with or without a TKI.
The patients all had Eastern Cooperative Oncology Group performance status of 0-2, and adequate liver function.
Patients with clinically significant cardiovascular disease or central nervous system disease pathology were excluded, except that patients with CNS leukemia could be enrolled.
The induction phase consisted of 30 mg ponatinib daily plus blinatumomab standard dosing on a 4-week-on, 2-week-off schedule. Patients in CMR, defined for frontline patients as undetectable BCR-ABL transcripts by polymerase chain reaction, then received up to four consolidation cycles of the regimen with ponatinib at a 15-mg dose, followed by 5 years of ponatinib 15-mg maintenance. All patients also received CNS prophylaxis with 12 cycles of intrathecal chemotherapy with alternating administration of methotrexate and cytarabine.
Of the 35 patients treated to date with the combination, 20 with Ph+ALL received it as frontline therapy and 10 received it for relapsed/refractory disease; 5 patients with CML in lymphoid blast phase also were treated.
High CMR, CR rates
As noted before, the CMR rate, the primary endpoint among patients with newly diagnosed Ph+ALL, was 85%, with a CR/CRp rate of 100%. Six of the patients in the frontline group and one in the salvage therapy group had CRs but were positive for minimal residual disease (MRD) at study outset.
The CR/CRp rate for the entire cohort of 28 patients (excluding those with a CR at start) was 96%, with only 1 patient who had relapsed/refractory disease not having a CR. This patient had received ponatinib in a prior salvage regimen.
The CMR rate among the entire cohort was 79%, with 85% of patients in the frontline ALL cohort having a CMR, 88% in the relapsed/refractory cohort, and 40% in the CML cohort. There were no early deaths among any patients.
“After one cycle of ponatinib plus blinatumomab, 84% of frontline patients had achieved at least a major molecular response, and 58% had achieved a CMR. Among those with relapsed/refractory Ph+ALL, 75% achieved CMR after one cycle of therapy,” Dr. Short said.
Of the 20 frontline patients in CR, one patient experienced visual changes and possible stroke that were considered possibly related to the study medication. This patient was taken off study. During a later maintenance regimen this patient developed a non-ST elevation myocardial infarction and died from postprocedural bleeding and hypovolemic shock following a cardiac catheterization procedure.
The remainder of patients in the frontline cohort had ongoing responses without the need for HSCT at last follow-up. There were no relapses, with a median duration of CR of 6 months,
Among the 10 with relapsed/refractory Ph+ALL, one did not have a response, and the remaining 9 had CR/CRps.
Of the latter groups, four went on to allogeneic HSCT and three were still alive; one patient who underwent a transplant experienced a relapse and died. One additional patient was alive with relapsed disease with T315I and E255V mutations at the time of relapse, one patient in CR who went off study due to insurance issues died from an unknown cause, and the three remaining patients had ongoing responses without transplant.
Among the five patients with CML in lymphoid blast phase, two had relapses, but both are still alive and currently in remission, and three have ongoing responses without transplant.
After a median follow-up of 12 months the 1-year event-free survival (EFS) rate for the entire 35-patient group was 76%, and the 2-year EFS was 70%.
The 1-year overall survival rate was 93%, and the 2-year OS rate was 80%.
Among patients in the frontline group, the 1-year and 2-year EFS and OS rates were all 93%.
For the relapsed/refractory cohort, the estimated 2-year EFS was 41% and OS was 53%. For the CML cohort, the 2-year EFS was 60%, with all patients still alive at last follow-up.
There were no grade 4 adverse events on study. Grade 3 adverse events considered at least possibly related to study treatment were elevated lipase, fever/febrile neutropenia, increased alanine aminotransferase, cerebrovascular ischemia, hypertension, pancreatitis, deep vein thrombosis, and encephalopathy. There were no cases of grade 3 cytokine release syndrome or tremor.
The study was sponsored by MD Anderson Cancer Center with collaboration from the National Cancer Institute, Amgen, and Takeda. Dr. Short has disclosed relationships with Amgen and Takeda. Dr. Nichols reported having no conflicts of interest.
For adults with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ALL), frontline therapy with the chemotherapy-free combination of ponatinib (Iclusig) and blinatumomab (Blincyto) shows promise as an alternative to early hematopoietic stem cell transplantation (HSCT), investigators in a single-arm phase 2 study reported.
In an interim analysis of the combination in patients with newly diagnosed or relapsed/refractory Ph+ALL or lymphoid accelerated or blast phase chronic myeloid leukemia (CML), 20 patients who received it as frontline therapy had a rate of complete responses (CR) or complete responses with partial recovery of blood counts (CRp) of 100% and a complete molecular remission (CMR) rate of 85%, reported Nicholas Short, MD, of the University of Texas MD Anderson Cancer Center in Houston.
“This translated into an estimated 2-year overall survival of 93%, with no patients undergoing transplant in first remission, and none having relapse at last follow-up,” he said in an oral abstract presented during the European Hematology Association annual congress.
Among patients with relapsed/refractory Ph+ALL, the CR/CRp rate was 89%, the CMR rate was 88%, and the estimated 2-year overall survival rate was 53%, he said.
Transplants on hold
“The big selling point is the ability to avoid stem cell transplant, which is not always the first thing you do in Ph-positive ALL, but it’s always on your mind,” said Gwen Nichols, MD, chief medical officer of the Leukemia and Lymphoma Society, who was not involved in the study.
“It looks, albeit with very limited follow-up, that patients haven’t relapsed yet such that transplant would be necessary. Anything we can do to avoid people having long-term complications that go along with an allogeneic transplant is a step in the right direction,” she said in an interview.
One combination, three cohorts
Ph+ALL comprises about 25% of all adult ALL. The standard of care in newly diagnosed patients is chemotherapy plus a tyrosine kinase inhibitor (TKI) targeted against the BCR-ABL transcript.
Ponatinib is a pan-BCR-ABL TKI that has been shown to have activity against ALL with T315I mutations, which are present in about 75% of the cases of relapsed disease, Dr. Short said.
Blinatumomab is a bi-specific T-cell engager (BiTe) that has been shown to be effective as monotherapy against relapsed/refractory Ph+ALL as monotherapy and in combination with dasatinib.
Dr. Short and colleagues enrolled patients with newly diagnosed or relapsed/refractory Ph+ALL or lymphoid accelerated or blast phase CML. Patients in the frontline cohort could have received one or two prior lines of chemotherapy with or without a TKI.
The patients all had Eastern Cooperative Oncology Group performance status of 0-2, and adequate liver function.
Patients with clinically significant cardiovascular disease or central nervous system disease pathology were excluded, except that patients with CNS leukemia could be enrolled.
The induction phase consisted of 30 mg ponatinib daily plus blinatumomab standard dosing on a 4-week-on, 2-week-off schedule. Patients in CMR, defined for frontline patients as undetectable BCR-ABL transcripts by polymerase chain reaction, then received up to four consolidation cycles of the regimen with ponatinib at a 15-mg dose, followed by 5 years of ponatinib 15-mg maintenance. All patients also received CNS prophylaxis with 12 cycles of intrathecal chemotherapy with alternating administration of methotrexate and cytarabine.
Of the 35 patients treated to date with the combination, 20 with Ph+ALL received it as frontline therapy and 10 received it for relapsed/refractory disease; 5 patients with CML in lymphoid blast phase also were treated.
High CMR, CR rates
As noted before, the CMR rate, the primary endpoint among patients with newly diagnosed Ph+ALL, was 85%, with a CR/CRp rate of 100%. Six of the patients in the frontline group and one in the salvage therapy group had CRs but were positive for minimal residual disease (MRD) at study outset.
The CR/CRp rate for the entire cohort of 28 patients (excluding those with a CR at start) was 96%, with only 1 patient who had relapsed/refractory disease not having a CR. This patient had received ponatinib in a prior salvage regimen.
The CMR rate among the entire cohort was 79%, with 85% of patients in the frontline ALL cohort having a CMR, 88% in the relapsed/refractory cohort, and 40% in the CML cohort. There were no early deaths among any patients.
“After one cycle of ponatinib plus blinatumomab, 84% of frontline patients had achieved at least a major molecular response, and 58% had achieved a CMR. Among those with relapsed/refractory Ph+ALL, 75% achieved CMR after one cycle of therapy,” Dr. Short said.
Of the 20 frontline patients in CR, one patient experienced visual changes and possible stroke that were considered possibly related to the study medication. This patient was taken off study. During a later maintenance regimen this patient developed a non-ST elevation myocardial infarction and died from postprocedural bleeding and hypovolemic shock following a cardiac catheterization procedure.
The remainder of patients in the frontline cohort had ongoing responses without the need for HSCT at last follow-up. There were no relapses, with a median duration of CR of 6 months,
Among the 10 with relapsed/refractory Ph+ALL, one did not have a response, and the remaining 9 had CR/CRps.
Of the latter groups, four went on to allogeneic HSCT and three were still alive; one patient who underwent a transplant experienced a relapse and died. One additional patient was alive with relapsed disease with T315I and E255V mutations at the time of relapse, one patient in CR who went off study due to insurance issues died from an unknown cause, and the three remaining patients had ongoing responses without transplant.
Among the five patients with CML in lymphoid blast phase, two had relapses, but both are still alive and currently in remission, and three have ongoing responses without transplant.
After a median follow-up of 12 months the 1-year event-free survival (EFS) rate for the entire 35-patient group was 76%, and the 2-year EFS was 70%.
The 1-year overall survival rate was 93%, and the 2-year OS rate was 80%.
Among patients in the frontline group, the 1-year and 2-year EFS and OS rates were all 93%.
For the relapsed/refractory cohort, the estimated 2-year EFS was 41% and OS was 53%. For the CML cohort, the 2-year EFS was 60%, with all patients still alive at last follow-up.
There were no grade 4 adverse events on study. Grade 3 adverse events considered at least possibly related to study treatment were elevated lipase, fever/febrile neutropenia, increased alanine aminotransferase, cerebrovascular ischemia, hypertension, pancreatitis, deep vein thrombosis, and encephalopathy. There were no cases of grade 3 cytokine release syndrome or tremor.
The study was sponsored by MD Anderson Cancer Center with collaboration from the National Cancer Institute, Amgen, and Takeda. Dr. Short has disclosed relationships with Amgen and Takeda. Dr. Nichols reported having no conflicts of interest.
For adults with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ALL), frontline therapy with the chemotherapy-free combination of ponatinib (Iclusig) and blinatumomab (Blincyto) shows promise as an alternative to early hematopoietic stem cell transplantation (HSCT), investigators in a single-arm phase 2 study reported.
In an interim analysis of the combination in patients with newly diagnosed or relapsed/refractory Ph+ALL or lymphoid accelerated or blast phase chronic myeloid leukemia (CML), 20 patients who received it as frontline therapy had a rate of complete responses (CR) or complete responses with partial recovery of blood counts (CRp) of 100% and a complete molecular remission (CMR) rate of 85%, reported Nicholas Short, MD, of the University of Texas MD Anderson Cancer Center in Houston.
“This translated into an estimated 2-year overall survival of 93%, with no patients undergoing transplant in first remission, and none having relapse at last follow-up,” he said in an oral abstract presented during the European Hematology Association annual congress.
Among patients with relapsed/refractory Ph+ALL, the CR/CRp rate was 89%, the CMR rate was 88%, and the estimated 2-year overall survival rate was 53%, he said.
Transplants on hold
“The big selling point is the ability to avoid stem cell transplant, which is not always the first thing you do in Ph-positive ALL, but it’s always on your mind,” said Gwen Nichols, MD, chief medical officer of the Leukemia and Lymphoma Society, who was not involved in the study.
“It looks, albeit with very limited follow-up, that patients haven’t relapsed yet such that transplant would be necessary. Anything we can do to avoid people having long-term complications that go along with an allogeneic transplant is a step in the right direction,” she said in an interview.
One combination, three cohorts
Ph+ALL comprises about 25% of all adult ALL. The standard of care in newly diagnosed patients is chemotherapy plus a tyrosine kinase inhibitor (TKI) targeted against the BCR-ABL transcript.
Ponatinib is a pan-BCR-ABL TKI that has been shown to have activity against ALL with T315I mutations, which are present in about 75% of the cases of relapsed disease, Dr. Short said.
Blinatumomab is a bi-specific T-cell engager (BiTe) that has been shown to be effective as monotherapy against relapsed/refractory Ph+ALL as monotherapy and in combination with dasatinib.
Dr. Short and colleagues enrolled patients with newly diagnosed or relapsed/refractory Ph+ALL or lymphoid accelerated or blast phase CML. Patients in the frontline cohort could have received one or two prior lines of chemotherapy with or without a TKI.
The patients all had Eastern Cooperative Oncology Group performance status of 0-2, and adequate liver function.
Patients with clinically significant cardiovascular disease or central nervous system disease pathology were excluded, except that patients with CNS leukemia could be enrolled.
The induction phase consisted of 30 mg ponatinib daily plus blinatumomab standard dosing on a 4-week-on, 2-week-off schedule. Patients in CMR, defined for frontline patients as undetectable BCR-ABL transcripts by polymerase chain reaction, then received up to four consolidation cycles of the regimen with ponatinib at a 15-mg dose, followed by 5 years of ponatinib 15-mg maintenance. All patients also received CNS prophylaxis with 12 cycles of intrathecal chemotherapy with alternating administration of methotrexate and cytarabine.
Of the 35 patients treated to date with the combination, 20 with Ph+ALL received it as frontline therapy and 10 received it for relapsed/refractory disease; 5 patients with CML in lymphoid blast phase also were treated.
High CMR, CR rates
As noted before, the CMR rate, the primary endpoint among patients with newly diagnosed Ph+ALL, was 85%, with a CR/CRp rate of 100%. Six of the patients in the frontline group and one in the salvage therapy group had CRs but were positive for minimal residual disease (MRD) at study outset.
The CR/CRp rate for the entire cohort of 28 patients (excluding those with a CR at start) was 96%, with only 1 patient who had relapsed/refractory disease not having a CR. This patient had received ponatinib in a prior salvage regimen.
The CMR rate among the entire cohort was 79%, with 85% of patients in the frontline ALL cohort having a CMR, 88% in the relapsed/refractory cohort, and 40% in the CML cohort. There were no early deaths among any patients.
“After one cycle of ponatinib plus blinatumomab, 84% of frontline patients had achieved at least a major molecular response, and 58% had achieved a CMR. Among those with relapsed/refractory Ph+ALL, 75% achieved CMR after one cycle of therapy,” Dr. Short said.
Of the 20 frontline patients in CR, one patient experienced visual changes and possible stroke that were considered possibly related to the study medication. This patient was taken off study. During a later maintenance regimen this patient developed a non-ST elevation myocardial infarction and died from postprocedural bleeding and hypovolemic shock following a cardiac catheterization procedure.
The remainder of patients in the frontline cohort had ongoing responses without the need for HSCT at last follow-up. There were no relapses, with a median duration of CR of 6 months,
Among the 10 with relapsed/refractory Ph+ALL, one did not have a response, and the remaining 9 had CR/CRps.
Of the latter groups, four went on to allogeneic HSCT and three were still alive; one patient who underwent a transplant experienced a relapse and died. One additional patient was alive with relapsed disease with T315I and E255V mutations at the time of relapse, one patient in CR who went off study due to insurance issues died from an unknown cause, and the three remaining patients had ongoing responses without transplant.
Among the five patients with CML in lymphoid blast phase, two had relapses, but both are still alive and currently in remission, and three have ongoing responses without transplant.
After a median follow-up of 12 months the 1-year event-free survival (EFS) rate for the entire 35-patient group was 76%, and the 2-year EFS was 70%.
The 1-year overall survival rate was 93%, and the 2-year OS rate was 80%.
Among patients in the frontline group, the 1-year and 2-year EFS and OS rates were all 93%.
For the relapsed/refractory cohort, the estimated 2-year EFS was 41% and OS was 53%. For the CML cohort, the 2-year EFS was 60%, with all patients still alive at last follow-up.
There were no grade 4 adverse events on study. Grade 3 adverse events considered at least possibly related to study treatment were elevated lipase, fever/febrile neutropenia, increased alanine aminotransferase, cerebrovascular ischemia, hypertension, pancreatitis, deep vein thrombosis, and encephalopathy. There were no cases of grade 3 cytokine release syndrome or tremor.
The study was sponsored by MD Anderson Cancer Center with collaboration from the National Cancer Institute, Amgen, and Takeda. Dr. Short has disclosed relationships with Amgen and Takeda. Dr. Nichols reported having no conflicts of interest.
FROM EHA 2021
HMAs benefit children with relapsed/refractory AML
Hypomethylating agents are generally considered to be agents of choice for older adults with acute myeloid leukemia who cannot tolerate the rigors of more intensive therapies, but HMAs also can serve as a bridge to transplant for children and young adults with relapsed or refractory acute myeloid leukemia.
That’s according to Himalee S. Sabnis, MD, MSc and colleagues at Emory University and the Aflac Cancer and Blood Disorders Center at Children’s Healthcare of Atlanta.
In a scientific poster presented during the annual meeting of the American Society of Pediatric Hematology/Oncology, the investigators reported results of a retrospective study of HMA use in patients with relapsed or refractory pediatric AML treated in their center.
Curative intent and palliation
They identified 25 patients (15 boys) with a median age of 8.3 years (range 1.4 to 21 years) with relapsed/refractory AML who received HMAs for curative intent prior to hematopoietic stem cell transplant (HSCT), palliation, or in combination with donor leukocyte infusion (DLI).
Of the 21 patients with relapsed disease, 16 were in first relapse and 5 were in second relapse or greater. Four of the patients had primary refractory disease. The cytogenetic and molecular features were KMT2A rearrangements in six patients, monosomy 7/deletion 7 q in four patients, 8;21 translocation in three patients, and FLT3-ITD mutations in four patients.
The patients received a median of 5.3 HMA cycles each. Of the 133 total HMA cycles, 87 were with azacitidine, and 46 were with decitabine.
HMAs were used as monotherapy in 62% of cycles, and in combination with other therapies in 38%. Of the combinations, 16 were with donor leukocyte infusion, and 9 were gemtuzumab ozogamicin (Mylotarg).
Of the 13 patients for whom HMAs were used as part of treatment plan with curative intent, 5 proceeded to HSCT, and 8 did not. Of the 5 patients, 1 died from transplant-related causes, and 4 were alive post transplant. Of the 8 patients who did not undergo transplant, 1 had chimeric antigen receptor T- cell (CAR T) therapy, and 7 experienced disease progression.
The mean duration of palliative care was 144 days, with patients receiving from one to nine cycles with an HMA, and no treatment interruptions due to toxicity.
Of 5 patients who received donor leukocyte infusions, 3 reached minimal residual disease negativity; all 3 of these patients had late relapses but remained long-term survivors, the investigators reported.
They concluded that “hypomethylating agents can be used effectively as a bridge to transplantation in relapsed and refractory AML with gemtuzumab ozogamicin being the most common agent for combination therapy. Palliation with HMAs is associated with low toxicity and high tolerability in relapsed/refractory AML. Use of HMAs with DLI can induce sustained remissions in some patients.”
The authors propose prospective clinical trials using HMAs in the relapsed/refractory pediatric AML setting in combination with gemtuzumab ozogamicin, alternative targeted agents, and chemotherapy.
HMAs in treatment-related AML
Shilpa Shahani, MD, a pediatric oncologist and assistant clinical professor of pediatrics at City of Hope in Duarte, Calif., who was not involved in the study, has experience administering HMAs primarily in the adolescent and young adult population with AML.
“Azacitidine and decitabine are good for treatment-related leukemias,” she said in an interview. “They can be used otherwise for people who have relapsed disease and are trying to navigate other options.”
Although they are not standard first-line agents in younger patients, HMAs can play a useful role in therapy for relapsed or refractory disease, she said.
The authors and Dr. Shahani reported having no conflicts of interest to disclose.
Hypomethylating agents are generally considered to be agents of choice for older adults with acute myeloid leukemia who cannot tolerate the rigors of more intensive therapies, but HMAs also can serve as a bridge to transplant for children and young adults with relapsed or refractory acute myeloid leukemia.
That’s according to Himalee S. Sabnis, MD, MSc and colleagues at Emory University and the Aflac Cancer and Blood Disorders Center at Children’s Healthcare of Atlanta.
In a scientific poster presented during the annual meeting of the American Society of Pediatric Hematology/Oncology, the investigators reported results of a retrospective study of HMA use in patients with relapsed or refractory pediatric AML treated in their center.
Curative intent and palliation
They identified 25 patients (15 boys) with a median age of 8.3 years (range 1.4 to 21 years) with relapsed/refractory AML who received HMAs for curative intent prior to hematopoietic stem cell transplant (HSCT), palliation, or in combination with donor leukocyte infusion (DLI).
Of the 21 patients with relapsed disease, 16 were in first relapse and 5 were in second relapse or greater. Four of the patients had primary refractory disease. The cytogenetic and molecular features were KMT2A rearrangements in six patients, monosomy 7/deletion 7 q in four patients, 8;21 translocation in three patients, and FLT3-ITD mutations in four patients.
The patients received a median of 5.3 HMA cycles each. Of the 133 total HMA cycles, 87 were with azacitidine, and 46 were with decitabine.
HMAs were used as monotherapy in 62% of cycles, and in combination with other therapies in 38%. Of the combinations, 16 were with donor leukocyte infusion, and 9 were gemtuzumab ozogamicin (Mylotarg).
Of the 13 patients for whom HMAs were used as part of treatment plan with curative intent, 5 proceeded to HSCT, and 8 did not. Of the 5 patients, 1 died from transplant-related causes, and 4 were alive post transplant. Of the 8 patients who did not undergo transplant, 1 had chimeric antigen receptor T- cell (CAR T) therapy, and 7 experienced disease progression.
The mean duration of palliative care was 144 days, with patients receiving from one to nine cycles with an HMA, and no treatment interruptions due to toxicity.
Of 5 patients who received donor leukocyte infusions, 3 reached minimal residual disease negativity; all 3 of these patients had late relapses but remained long-term survivors, the investigators reported.
They concluded that “hypomethylating agents can be used effectively as a bridge to transplantation in relapsed and refractory AML with gemtuzumab ozogamicin being the most common agent for combination therapy. Palliation with HMAs is associated with low toxicity and high tolerability in relapsed/refractory AML. Use of HMAs with DLI can induce sustained remissions in some patients.”
The authors propose prospective clinical trials using HMAs in the relapsed/refractory pediatric AML setting in combination with gemtuzumab ozogamicin, alternative targeted agents, and chemotherapy.
HMAs in treatment-related AML
Shilpa Shahani, MD, a pediatric oncologist and assistant clinical professor of pediatrics at City of Hope in Duarte, Calif., who was not involved in the study, has experience administering HMAs primarily in the adolescent and young adult population with AML.
“Azacitidine and decitabine are good for treatment-related leukemias,” she said in an interview. “They can be used otherwise for people who have relapsed disease and are trying to navigate other options.”
Although they are not standard first-line agents in younger patients, HMAs can play a useful role in therapy for relapsed or refractory disease, she said.
The authors and Dr. Shahani reported having no conflicts of interest to disclose.
Hypomethylating agents are generally considered to be agents of choice for older adults with acute myeloid leukemia who cannot tolerate the rigors of more intensive therapies, but HMAs also can serve as a bridge to transplant for children and young adults with relapsed or refractory acute myeloid leukemia.
That’s according to Himalee S. Sabnis, MD, MSc and colleagues at Emory University and the Aflac Cancer and Blood Disorders Center at Children’s Healthcare of Atlanta.
In a scientific poster presented during the annual meeting of the American Society of Pediatric Hematology/Oncology, the investigators reported results of a retrospective study of HMA use in patients with relapsed or refractory pediatric AML treated in their center.
Curative intent and palliation
They identified 25 patients (15 boys) with a median age of 8.3 years (range 1.4 to 21 years) with relapsed/refractory AML who received HMAs for curative intent prior to hematopoietic stem cell transplant (HSCT), palliation, or in combination with donor leukocyte infusion (DLI).
Of the 21 patients with relapsed disease, 16 were in first relapse and 5 were in second relapse or greater. Four of the patients had primary refractory disease. The cytogenetic and molecular features were KMT2A rearrangements in six patients, monosomy 7/deletion 7 q in four patients, 8;21 translocation in three patients, and FLT3-ITD mutations in four patients.
The patients received a median of 5.3 HMA cycles each. Of the 133 total HMA cycles, 87 were with azacitidine, and 46 were with decitabine.
HMAs were used as monotherapy in 62% of cycles, and in combination with other therapies in 38%. Of the combinations, 16 were with donor leukocyte infusion, and 9 were gemtuzumab ozogamicin (Mylotarg).
Of the 13 patients for whom HMAs were used as part of treatment plan with curative intent, 5 proceeded to HSCT, and 8 did not. Of the 5 patients, 1 died from transplant-related causes, and 4 were alive post transplant. Of the 8 patients who did not undergo transplant, 1 had chimeric antigen receptor T- cell (CAR T) therapy, and 7 experienced disease progression.
The mean duration of palliative care was 144 days, with patients receiving from one to nine cycles with an HMA, and no treatment interruptions due to toxicity.
Of 5 patients who received donor leukocyte infusions, 3 reached minimal residual disease negativity; all 3 of these patients had late relapses but remained long-term survivors, the investigators reported.
They concluded that “hypomethylating agents can be used effectively as a bridge to transplantation in relapsed and refractory AML with gemtuzumab ozogamicin being the most common agent for combination therapy. Palliation with HMAs is associated with low toxicity and high tolerability in relapsed/refractory AML. Use of HMAs with DLI can induce sustained remissions in some patients.”
The authors propose prospective clinical trials using HMAs in the relapsed/refractory pediatric AML setting in combination with gemtuzumab ozogamicin, alternative targeted agents, and chemotherapy.
HMAs in treatment-related AML
Shilpa Shahani, MD, a pediatric oncologist and assistant clinical professor of pediatrics at City of Hope in Duarte, Calif., who was not involved in the study, has experience administering HMAs primarily in the adolescent and young adult population with AML.
“Azacitidine and decitabine are good for treatment-related leukemias,” she said in an interview. “They can be used otherwise for people who have relapsed disease and are trying to navigate other options.”
Although they are not standard first-line agents in younger patients, HMAs can play a useful role in therapy for relapsed or refractory disease, she said.
The authors and Dr. Shahani reported having no conflicts of interest to disclose.
FROM THE 2021 ASPHO CONFERENCE
Reduced-intensity transplant benefits older patients with AML
Among older patients with acute myeloid leukemia (AML), survival is significantly better when they undergo reduced-intensity conditioning (RIC) before receiving an allogeneic hematopoietic cell transplant (HCT) at first remission. This improvement in survival is seen regardless of key factors such as genotype and the status of minimal residual disease (MRD) after initial chemotherapy, results from two large randomized trials show.
“Two consecutive trials of more than 1,500 older AML patients above 60 years of age demonstrate a consistent benefit for RIC transplant in first remission,” said first author Nigel Russell, MD, of Guy’s Hospital, London, and Nottingham University, England. “This benefit is seen independent of their post-course 1 MRD status,” he added.
Dr. Russell presented the new data at the European Hematology Association (EHA) 2021 Annual Meeting.
Commenting on the study, Charles Craddock, MD, said in an interview that the results “confirm the growing importance of RIC transplantation as a central treatment management strategy in high-risk AML and in this population high risk patients over 60.”
“[These findings] reinforce the evolving treatment paradigm that, in fit adults over 60 with AML, hematopoietic cell transplantation should be considered an essential component of their management plan,” said Dr. Craddock, academic director of the Center for Clinical Haematology, Queen Elizabeth Hospital, Birmingham, England.
Patients with AML who are older than 60 years can achieve complete remission with intensive chemotherapy alone; however, relapse is common, and only about 20% survive for 5 years, Dr. Russell explained.
HCT significantly improves survival outcomes, and the development of RIC has made transplantation accessible to high-risk patients by making the procedure more tolerable with lower toxicity in comparison with conventional conditioning regimens.
However, there is ongoing debate over the prognostic effect of key factors in pretransplant conditioning that may be predictive of the risk for post-transplant relapse – in particular, the presence of MRD after the first course of conditioning, he explained.
To more closely investigate those factors and the rate of survival of older patients with AML who undergo RIC transplant, Dr. Russell and his colleagues evaluated results from the National Cancer Research Institute’s (NCRI) AML16 trial, which was conducted from 2006 to 2012, and interim results from the NCRI AML18 trial, which started in 2015 and is ongoing.
Both trials employed double induction of daunorubicin and clofarabine or, in the AML16 trial, AraC ± gemtuzumab, and in the AML18 trial, daunorubicin and AraC (DA) + gemtuzumab.
In AML18, patients who were MRD positive after course 1 were randomly assigned to undergo either an intensification randomization after either FLAG-Ida or DA+cladribine or DA alone.
In AML16, of 983 patients in first complete response, 144 (15%) subsequently underwent RIC transplant. The median follow-up for survival from complete response was 45 months.
In the AML18 trial, of 847 patients, 648 patients achieved complete response. Among them, 201 (31%) underwent transplant. The median follow-up of survival was 45 months.
The results of both trials showed greater benefit with RIC transplant versus chemotherapy alone.
In the AML16 trial, among patients aged 60 to 70 who received RIC, survival at 5 years was significantly improved compared with chemotherapy alone (37% vs. 19%; hazard ratio, 0.65; 95% confidence interval, 0.52-0.82; P < .001).
In AML16, the higher survival benefit in comparison with chemotherapy alone was observed in the RIC group across subgroups of risk level, as stratified according to in the multivariate Wheatley risk group score. Subgroup stratification was based on age, cytogenics, and other factors (HR, 0.66; 95% CI, 0.53-0.83; P < .001).
Importantly, the survival benefits were significantly greater with RIC transplant regardless of MRD-negative or MRD-positive status after course 1 (HR, 0.68; 95% CI, 0.54-0.85; P < .001).
Allograft transplant was also more favorable regardless of FLT3 ITD or NPM1 mutation status (P for heterogeneity by genetic subgroups, 0.61).
In AML16, no groups were found to have benefited more with RIC. Consequently, the criteria for transplant in AML18 trial were based on patients’ health status and donor availability.
An interim analysis of the ongoing AML 18 trial further underscored an overall benefit of RIC transplant. Rates of 3-year survival from remission were 48% with RIC transplant, versus 37.4% with chemotherapy alone (P = .027). The benefit was independent of MRD status after conditioning course 1, similar to the AML16 results (HR, 0.71; 95% CI, 0.54-0.95; P = .02).
Although the rate of transplantation in the AML18 trial was higher among patients who were MRD positive in comparison with those who were MRD negative (36% vs. 24.8%), the rates of post-transplant survival were not significantly different between those who were MRD positive and those who were MRD negative after course 1 (51.1% vs. 46.6% at 3 years; P = .84).
The authors evaluated the effects of a second conditioning course on transplant outcomes among patients who did not initially achieve an MRD-negative complete remission.
They found that 60% of patients did convert from MRD-positive to MRD-negative status after course 2. Among those patients, the survival versus chemotherapy alone was substantially higher (HR, 0.32; 95% CI, 0.11-0.92) compared to those who remained MRD-negative (HR 0.74; 95% CI, 0.32-1.72).
However, the authors note that, owing to a lack of heterogeneity, the results don’t necessarily mean that the patients who remained MRD positive did not also benefit from transplant.
“There was a significant benefit for transplant in those who converted to MRD negativity,” Dr. Russell said.
“With a hazard ratio of .32, this was far superior to those who remained MRD-positive post course 2,” he said.
“These results show that MRD status after course 1 is important information in terms of response to therapy and can alter your treatment strategy if you’re considering a transplant as an option for these patients,” Dr. Russell told this news organization.
In further commenting, Dr. Craddock said the research highlights the importance of randomized trials with regard to whether patients who are MRD-positive before transplant will benefit from an additional course of therapy to reduce the MRD load.
“Most get two courses, but the question is, if they are still MRD positive, should they get a third course, and if so, what should that look like?” he said.
“There are currently no randomized controlled trials to address that ongoing question, and they need to be done,” he added.
Dr. Russell has relationships with Pfizer, Astellas, and Jazz Pharma. Dr. Craddock has a relationship with Bristol-Myers Squibb.
A version of this article first appeared on Medscape.com.
Among older patients with acute myeloid leukemia (AML), survival is significantly better when they undergo reduced-intensity conditioning (RIC) before receiving an allogeneic hematopoietic cell transplant (HCT) at first remission. This improvement in survival is seen regardless of key factors such as genotype and the status of minimal residual disease (MRD) after initial chemotherapy, results from two large randomized trials show.
“Two consecutive trials of more than 1,500 older AML patients above 60 years of age demonstrate a consistent benefit for RIC transplant in first remission,” said first author Nigel Russell, MD, of Guy’s Hospital, London, and Nottingham University, England. “This benefit is seen independent of their post-course 1 MRD status,” he added.
Dr. Russell presented the new data at the European Hematology Association (EHA) 2021 Annual Meeting.
Commenting on the study, Charles Craddock, MD, said in an interview that the results “confirm the growing importance of RIC transplantation as a central treatment management strategy in high-risk AML and in this population high risk patients over 60.”
“[These findings] reinforce the evolving treatment paradigm that, in fit adults over 60 with AML, hematopoietic cell transplantation should be considered an essential component of their management plan,” said Dr. Craddock, academic director of the Center for Clinical Haematology, Queen Elizabeth Hospital, Birmingham, England.
Patients with AML who are older than 60 years can achieve complete remission with intensive chemotherapy alone; however, relapse is common, and only about 20% survive for 5 years, Dr. Russell explained.
HCT significantly improves survival outcomes, and the development of RIC has made transplantation accessible to high-risk patients by making the procedure more tolerable with lower toxicity in comparison with conventional conditioning regimens.
However, there is ongoing debate over the prognostic effect of key factors in pretransplant conditioning that may be predictive of the risk for post-transplant relapse – in particular, the presence of MRD after the first course of conditioning, he explained.
To more closely investigate those factors and the rate of survival of older patients with AML who undergo RIC transplant, Dr. Russell and his colleagues evaluated results from the National Cancer Research Institute’s (NCRI) AML16 trial, which was conducted from 2006 to 2012, and interim results from the NCRI AML18 trial, which started in 2015 and is ongoing.
Both trials employed double induction of daunorubicin and clofarabine or, in the AML16 trial, AraC ± gemtuzumab, and in the AML18 trial, daunorubicin and AraC (DA) + gemtuzumab.
In AML18, patients who were MRD positive after course 1 were randomly assigned to undergo either an intensification randomization after either FLAG-Ida or DA+cladribine or DA alone.
In AML16, of 983 patients in first complete response, 144 (15%) subsequently underwent RIC transplant. The median follow-up for survival from complete response was 45 months.
In the AML18 trial, of 847 patients, 648 patients achieved complete response. Among them, 201 (31%) underwent transplant. The median follow-up of survival was 45 months.
The results of both trials showed greater benefit with RIC transplant versus chemotherapy alone.
In the AML16 trial, among patients aged 60 to 70 who received RIC, survival at 5 years was significantly improved compared with chemotherapy alone (37% vs. 19%; hazard ratio, 0.65; 95% confidence interval, 0.52-0.82; P < .001).
In AML16, the higher survival benefit in comparison with chemotherapy alone was observed in the RIC group across subgroups of risk level, as stratified according to in the multivariate Wheatley risk group score. Subgroup stratification was based on age, cytogenics, and other factors (HR, 0.66; 95% CI, 0.53-0.83; P < .001).
Importantly, the survival benefits were significantly greater with RIC transplant regardless of MRD-negative or MRD-positive status after course 1 (HR, 0.68; 95% CI, 0.54-0.85; P < .001).
Allograft transplant was also more favorable regardless of FLT3 ITD or NPM1 mutation status (P for heterogeneity by genetic subgroups, 0.61).
In AML16, no groups were found to have benefited more with RIC. Consequently, the criteria for transplant in AML18 trial were based on patients’ health status and donor availability.
An interim analysis of the ongoing AML 18 trial further underscored an overall benefit of RIC transplant. Rates of 3-year survival from remission were 48% with RIC transplant, versus 37.4% with chemotherapy alone (P = .027). The benefit was independent of MRD status after conditioning course 1, similar to the AML16 results (HR, 0.71; 95% CI, 0.54-0.95; P = .02).
Although the rate of transplantation in the AML18 trial was higher among patients who were MRD positive in comparison with those who were MRD negative (36% vs. 24.8%), the rates of post-transplant survival were not significantly different between those who were MRD positive and those who were MRD negative after course 1 (51.1% vs. 46.6% at 3 years; P = .84).
The authors evaluated the effects of a second conditioning course on transplant outcomes among patients who did not initially achieve an MRD-negative complete remission.
They found that 60% of patients did convert from MRD-positive to MRD-negative status after course 2. Among those patients, the survival versus chemotherapy alone was substantially higher (HR, 0.32; 95% CI, 0.11-0.92) compared to those who remained MRD-negative (HR 0.74; 95% CI, 0.32-1.72).
However, the authors note that, owing to a lack of heterogeneity, the results don’t necessarily mean that the patients who remained MRD positive did not also benefit from transplant.
“There was a significant benefit for transplant in those who converted to MRD negativity,” Dr. Russell said.
“With a hazard ratio of .32, this was far superior to those who remained MRD-positive post course 2,” he said.
“These results show that MRD status after course 1 is important information in terms of response to therapy and can alter your treatment strategy if you’re considering a transplant as an option for these patients,” Dr. Russell told this news organization.
In further commenting, Dr. Craddock said the research highlights the importance of randomized trials with regard to whether patients who are MRD-positive before transplant will benefit from an additional course of therapy to reduce the MRD load.
“Most get two courses, but the question is, if they are still MRD positive, should they get a third course, and if so, what should that look like?” he said.
“There are currently no randomized controlled trials to address that ongoing question, and they need to be done,” he added.
Dr. Russell has relationships with Pfizer, Astellas, and Jazz Pharma. Dr. Craddock has a relationship with Bristol-Myers Squibb.
A version of this article first appeared on Medscape.com.
Among older patients with acute myeloid leukemia (AML), survival is significantly better when they undergo reduced-intensity conditioning (RIC) before receiving an allogeneic hematopoietic cell transplant (HCT) at first remission. This improvement in survival is seen regardless of key factors such as genotype and the status of minimal residual disease (MRD) after initial chemotherapy, results from two large randomized trials show.
“Two consecutive trials of more than 1,500 older AML patients above 60 years of age demonstrate a consistent benefit for RIC transplant in first remission,” said first author Nigel Russell, MD, of Guy’s Hospital, London, and Nottingham University, England. “This benefit is seen independent of their post-course 1 MRD status,” he added.
Dr. Russell presented the new data at the European Hematology Association (EHA) 2021 Annual Meeting.
Commenting on the study, Charles Craddock, MD, said in an interview that the results “confirm the growing importance of RIC transplantation as a central treatment management strategy in high-risk AML and in this population high risk patients over 60.”
“[These findings] reinforce the evolving treatment paradigm that, in fit adults over 60 with AML, hematopoietic cell transplantation should be considered an essential component of their management plan,” said Dr. Craddock, academic director of the Center for Clinical Haematology, Queen Elizabeth Hospital, Birmingham, England.
Patients with AML who are older than 60 years can achieve complete remission with intensive chemotherapy alone; however, relapse is common, and only about 20% survive for 5 years, Dr. Russell explained.
HCT significantly improves survival outcomes, and the development of RIC has made transplantation accessible to high-risk patients by making the procedure more tolerable with lower toxicity in comparison with conventional conditioning regimens.
However, there is ongoing debate over the prognostic effect of key factors in pretransplant conditioning that may be predictive of the risk for post-transplant relapse – in particular, the presence of MRD after the first course of conditioning, he explained.
To more closely investigate those factors and the rate of survival of older patients with AML who undergo RIC transplant, Dr. Russell and his colleagues evaluated results from the National Cancer Research Institute’s (NCRI) AML16 trial, which was conducted from 2006 to 2012, and interim results from the NCRI AML18 trial, which started in 2015 and is ongoing.
Both trials employed double induction of daunorubicin and clofarabine or, in the AML16 trial, AraC ± gemtuzumab, and in the AML18 trial, daunorubicin and AraC (DA) + gemtuzumab.
In AML18, patients who were MRD positive after course 1 were randomly assigned to undergo either an intensification randomization after either FLAG-Ida or DA+cladribine or DA alone.
In AML16, of 983 patients in first complete response, 144 (15%) subsequently underwent RIC transplant. The median follow-up for survival from complete response was 45 months.
In the AML18 trial, of 847 patients, 648 patients achieved complete response. Among them, 201 (31%) underwent transplant. The median follow-up of survival was 45 months.
The results of both trials showed greater benefit with RIC transplant versus chemotherapy alone.
In the AML16 trial, among patients aged 60 to 70 who received RIC, survival at 5 years was significantly improved compared with chemotherapy alone (37% vs. 19%; hazard ratio, 0.65; 95% confidence interval, 0.52-0.82; P < .001).
In AML16, the higher survival benefit in comparison with chemotherapy alone was observed in the RIC group across subgroups of risk level, as stratified according to in the multivariate Wheatley risk group score. Subgroup stratification was based on age, cytogenics, and other factors (HR, 0.66; 95% CI, 0.53-0.83; P < .001).
Importantly, the survival benefits were significantly greater with RIC transplant regardless of MRD-negative or MRD-positive status after course 1 (HR, 0.68; 95% CI, 0.54-0.85; P < .001).
Allograft transplant was also more favorable regardless of FLT3 ITD or NPM1 mutation status (P for heterogeneity by genetic subgroups, 0.61).
In AML16, no groups were found to have benefited more with RIC. Consequently, the criteria for transplant in AML18 trial were based on patients’ health status and donor availability.
An interim analysis of the ongoing AML 18 trial further underscored an overall benefit of RIC transplant. Rates of 3-year survival from remission were 48% with RIC transplant, versus 37.4% with chemotherapy alone (P = .027). The benefit was independent of MRD status after conditioning course 1, similar to the AML16 results (HR, 0.71; 95% CI, 0.54-0.95; P = .02).
Although the rate of transplantation in the AML18 trial was higher among patients who were MRD positive in comparison with those who were MRD negative (36% vs. 24.8%), the rates of post-transplant survival were not significantly different between those who were MRD positive and those who were MRD negative after course 1 (51.1% vs. 46.6% at 3 years; P = .84).
The authors evaluated the effects of a second conditioning course on transplant outcomes among patients who did not initially achieve an MRD-negative complete remission.
They found that 60% of patients did convert from MRD-positive to MRD-negative status after course 2. Among those patients, the survival versus chemotherapy alone was substantially higher (HR, 0.32; 95% CI, 0.11-0.92) compared to those who remained MRD-negative (HR 0.74; 95% CI, 0.32-1.72).
However, the authors note that, owing to a lack of heterogeneity, the results don’t necessarily mean that the patients who remained MRD positive did not also benefit from transplant.
“There was a significant benefit for transplant in those who converted to MRD negativity,” Dr. Russell said.
“With a hazard ratio of .32, this was far superior to those who remained MRD-positive post course 2,” he said.
“These results show that MRD status after course 1 is important information in terms of response to therapy and can alter your treatment strategy if you’re considering a transplant as an option for these patients,” Dr. Russell told this news organization.
In further commenting, Dr. Craddock said the research highlights the importance of randomized trials with regard to whether patients who are MRD-positive before transplant will benefit from an additional course of therapy to reduce the MRD load.
“Most get two courses, but the question is, if they are still MRD positive, should they get a third course, and if so, what should that look like?” he said.
“There are currently no randomized controlled trials to address that ongoing question, and they need to be done,” he added.
Dr. Russell has relationships with Pfizer, Astellas, and Jazz Pharma. Dr. Craddock has a relationship with Bristol-Myers Squibb.
A version of this article first appeared on Medscape.com.
CAR T cells rescue younger children with relapsed/refractory ALL
Even the youngest patients with relapsed or refractory B-lineage acute lymphoblastic leukemia (B-ALL) may be able to benefit from chimeric antigen reception T-cell (CAR T) therapy, investigators in an international consortium say.
Among 30 children aged under 2 years at the time of (B-ALL diagnosis, manufacturing of the CAR T product tisagenlecleucel (Kymriah) was feasible in 28 patients, and treatment resulted in high rates of minimal residual disease (MRD) negativity, complete responses, event-free survival, and overall survival, reported Sara Ghorashian, MD from the University College London Great Ormond Street Institute of Child Health, on behalf of the International BFM Resistant Disease Committee.
“The disease-related outcomes noted in this cohort of younger children predominantly with relapsed/refractory infant [mixed lineage leukemia]–rearranged ALL were at least as good as for the ELIANA study,” she said in an oral abstract presented during the European Hematology Association annual congress (Abstract S116).
The international, single-arm, open-label, ELIANA study was a phase 2 trial that included 97 patients aged 3-24 years with relapsed or refractory B-cell ALL, most of whom had previously undergone a hematopoietic stem cell transplant. Of those patients, 79 patients went on to receive a single infusion of the CAR T therapy.
“It’s fantastic data,” said Kevin J. Curran, MD, a pediatric hematologist/oncologist specializing in stem cell transplants and cellular therapy at Memorial Sloan Kettering Cancer Center, New York.
“Pediatric leukemia, while it’s the most common malignancy that happens in children, when you get down to this really small group, this under 3-year-old group, it’s hard to get a cohort, and for them to put together 30 patients, and show these great results is groundbreaking,” he said in an interview.
“Most importantly, it gives hope to parents who have young children who have really difficult to treat leukemia,” he said.
Dr. Curran was not involved in the study.
Scarce data on ALL in infants
“Children under 3 years of age were excluded from the ELIANA study, yet in terms of having often highly aggressive disease, with traditionally poor outcomes with conventional therapy, the need for novel forms of therapy for children with relapsed infant ALL is important,” Dr. Ghorashian said.
Because there is a paucity of data on outcomes in the youngest children, some health authorities will not support the use of tisagenlecleucel in this age group, and there are concerns about difficulties with performing leukapheresis in children weighing less than 10 kg, she noted.
To gain a better understanding of outcomes, members of the International BFM (Berlin-Frankfurt-Munster) Study Group conducted a retrospective analysis of data on all patients assessed for tisagenlecleucel for B-ALL who were aged under 3 years at screening at 1 of 15 centers in Europe and Israel.
A total of 30 patients were screened and had T cells harvested. Of this group, three patients did not receive CAR T infusions, two because of manufacturing failures, and one because of progressive disease.
Of the 27 patients who received CAR T infusions, 26 were evaluable for disease outcomes (1 had yet to reach the 30-day post infusion at the time of data cutoff).
The median age at diagnosis was 4.4 months, and the median age at infusion was 17.4 months; 19 of the 30 children in the entire cohort were boys. Mixed lineage leukemia rearrangements were found in 24 children, and 21 had undergone a stem cell transplant.
The children had a median of two prior lines of therapy, not including transplant. Seven of the children had received inotuzumab (Besponsa) and 11 had received blinotumumab (Blincyto).
High success rate
Of the 27 patients infused, 17 had sufficient cells harvested in a single day, and the remainder required 2-4 days. As noted, the CAR T product was successfully manufactured in 28 patients, with a median dose of 2.3 x 106/kg of patient weight.
The treatment failed for 2 of the 26 efficacy-evaluable patients, resulting in an MRD-negative rate of 92%.
Event-free survival at 6 months was 67%, similar to that in ELIANA (73%), and the 12-month event-free survival was 58%, which was superior to that in ELIANA (50%).
The 6-month and 12-month overall survival rates among the younger children were identical at 88%, compared with 90% and 76%, respectively, in ELIANA.
The 6- and 12-month probability of ongoing B-cell depletion, indicating CAR T persistence, were 77% and 68%, respectively. In ELIANA, the 6-month probability of B-cell depletion was 83%.
A total of 10 of the 27 patients received further therapy, including 3 who were given maintenance therapy for poor CAR T persistence, 2 who underwent chemotherapy for relapse, and 5 who underwent allogeneic stem cell transplant.
Of six patients who experienced a relapse after having a complete response, two had CD19 relapse.
Low rate of serious CRS
At 30 days post infusion, grade 3 or greater cytokine release syndrome (CRS) had occurred in two patients, severe neurotoxicity occurred in one, and grade 3 or greater prolonged cytopenias occurred in eight patients.
The toxicity profile in this study was generally favorable in comparison with ELIANA, with shorter median duration of CRS, shorter median duration of CRS-related ICU stay, and a lower frequency of tocilizumab use. It should be noted, however, that the I-BFM investigators used American Society for Transplantation and Cellular Therapy CRS consenus criteria, whereas the ELIANA investigators used University of Pennsylvania criteria.
“If the longer-term follow-up data are encouraging, it might suggest that the outcomes from tisagenlecleucel therapy are comparable to that of stem cell transplantation in high-risk relapsed infant ALL, without the associated late effects, and possibly supports CAR T-cell therapy eventually replace stem cell transplantation in this setting,” Dr. Ghorashian said.
Dr. Curran, who leads the CAR T effort at MSK Kids, the children’s division of MSKCC, agreed that the goal is for CAR T to replace stem cell transplants.
“I hope I put my clinical practice out of business with my research practice,” he said, but added that “I think we need to do more research in figuring out how to best use CAR T cells, either earlier, or as some data suggest, by treating patients with lower disease burden we would get better durability.
“Because obviously in kids’ cancer one relapse is too much, and we want to be able to raise that bar and provide hope and a cure for all of our children,” he said.
The study was sponsored by the I-BFM Resistant Disease Committee and member institutions. Dr. Ghorashian disclosed advisory board activity for Novartis, maker of tisagenlecleucel, and patents and royalties from UCL Business. Dr. Curran research funding and consulting fees from Novartis.
Even the youngest patients with relapsed or refractory B-lineage acute lymphoblastic leukemia (B-ALL) may be able to benefit from chimeric antigen reception T-cell (CAR T) therapy, investigators in an international consortium say.
Among 30 children aged under 2 years at the time of (B-ALL diagnosis, manufacturing of the CAR T product tisagenlecleucel (Kymriah) was feasible in 28 patients, and treatment resulted in high rates of minimal residual disease (MRD) negativity, complete responses, event-free survival, and overall survival, reported Sara Ghorashian, MD from the University College London Great Ormond Street Institute of Child Health, on behalf of the International BFM Resistant Disease Committee.
“The disease-related outcomes noted in this cohort of younger children predominantly with relapsed/refractory infant [mixed lineage leukemia]–rearranged ALL were at least as good as for the ELIANA study,” she said in an oral abstract presented during the European Hematology Association annual congress (Abstract S116).
The international, single-arm, open-label, ELIANA study was a phase 2 trial that included 97 patients aged 3-24 years with relapsed or refractory B-cell ALL, most of whom had previously undergone a hematopoietic stem cell transplant. Of those patients, 79 patients went on to receive a single infusion of the CAR T therapy.
“It’s fantastic data,” said Kevin J. Curran, MD, a pediatric hematologist/oncologist specializing in stem cell transplants and cellular therapy at Memorial Sloan Kettering Cancer Center, New York.
“Pediatric leukemia, while it’s the most common malignancy that happens in children, when you get down to this really small group, this under 3-year-old group, it’s hard to get a cohort, and for them to put together 30 patients, and show these great results is groundbreaking,” he said in an interview.
“Most importantly, it gives hope to parents who have young children who have really difficult to treat leukemia,” he said.
Dr. Curran was not involved in the study.
Scarce data on ALL in infants
“Children under 3 years of age were excluded from the ELIANA study, yet in terms of having often highly aggressive disease, with traditionally poor outcomes with conventional therapy, the need for novel forms of therapy for children with relapsed infant ALL is important,” Dr. Ghorashian said.
Because there is a paucity of data on outcomes in the youngest children, some health authorities will not support the use of tisagenlecleucel in this age group, and there are concerns about difficulties with performing leukapheresis in children weighing less than 10 kg, she noted.
To gain a better understanding of outcomes, members of the International BFM (Berlin-Frankfurt-Munster) Study Group conducted a retrospective analysis of data on all patients assessed for tisagenlecleucel for B-ALL who were aged under 3 years at screening at 1 of 15 centers in Europe and Israel.
A total of 30 patients were screened and had T cells harvested. Of this group, three patients did not receive CAR T infusions, two because of manufacturing failures, and one because of progressive disease.
Of the 27 patients who received CAR T infusions, 26 were evaluable for disease outcomes (1 had yet to reach the 30-day post infusion at the time of data cutoff).
The median age at diagnosis was 4.4 months, and the median age at infusion was 17.4 months; 19 of the 30 children in the entire cohort were boys. Mixed lineage leukemia rearrangements were found in 24 children, and 21 had undergone a stem cell transplant.
The children had a median of two prior lines of therapy, not including transplant. Seven of the children had received inotuzumab (Besponsa) and 11 had received blinotumumab (Blincyto).
High success rate
Of the 27 patients infused, 17 had sufficient cells harvested in a single day, and the remainder required 2-4 days. As noted, the CAR T product was successfully manufactured in 28 patients, with a median dose of 2.3 x 106/kg of patient weight.
The treatment failed for 2 of the 26 efficacy-evaluable patients, resulting in an MRD-negative rate of 92%.
Event-free survival at 6 months was 67%, similar to that in ELIANA (73%), and the 12-month event-free survival was 58%, which was superior to that in ELIANA (50%).
The 6-month and 12-month overall survival rates among the younger children were identical at 88%, compared with 90% and 76%, respectively, in ELIANA.
The 6- and 12-month probability of ongoing B-cell depletion, indicating CAR T persistence, were 77% and 68%, respectively. In ELIANA, the 6-month probability of B-cell depletion was 83%.
A total of 10 of the 27 patients received further therapy, including 3 who were given maintenance therapy for poor CAR T persistence, 2 who underwent chemotherapy for relapse, and 5 who underwent allogeneic stem cell transplant.
Of six patients who experienced a relapse after having a complete response, two had CD19 relapse.
Low rate of serious CRS
At 30 days post infusion, grade 3 or greater cytokine release syndrome (CRS) had occurred in two patients, severe neurotoxicity occurred in one, and grade 3 or greater prolonged cytopenias occurred in eight patients.
The toxicity profile in this study was generally favorable in comparison with ELIANA, with shorter median duration of CRS, shorter median duration of CRS-related ICU stay, and a lower frequency of tocilizumab use. It should be noted, however, that the I-BFM investigators used American Society for Transplantation and Cellular Therapy CRS consenus criteria, whereas the ELIANA investigators used University of Pennsylvania criteria.
“If the longer-term follow-up data are encouraging, it might suggest that the outcomes from tisagenlecleucel therapy are comparable to that of stem cell transplantation in high-risk relapsed infant ALL, without the associated late effects, and possibly supports CAR T-cell therapy eventually replace stem cell transplantation in this setting,” Dr. Ghorashian said.
Dr. Curran, who leads the CAR T effort at MSK Kids, the children’s division of MSKCC, agreed that the goal is for CAR T to replace stem cell transplants.
“I hope I put my clinical practice out of business with my research practice,” he said, but added that “I think we need to do more research in figuring out how to best use CAR T cells, either earlier, or as some data suggest, by treating patients with lower disease burden we would get better durability.
“Because obviously in kids’ cancer one relapse is too much, and we want to be able to raise that bar and provide hope and a cure for all of our children,” he said.
The study was sponsored by the I-BFM Resistant Disease Committee and member institutions. Dr. Ghorashian disclosed advisory board activity for Novartis, maker of tisagenlecleucel, and patents and royalties from UCL Business. Dr. Curran research funding and consulting fees from Novartis.
Even the youngest patients with relapsed or refractory B-lineage acute lymphoblastic leukemia (B-ALL) may be able to benefit from chimeric antigen reception T-cell (CAR T) therapy, investigators in an international consortium say.
Among 30 children aged under 2 years at the time of (B-ALL diagnosis, manufacturing of the CAR T product tisagenlecleucel (Kymriah) was feasible in 28 patients, and treatment resulted in high rates of minimal residual disease (MRD) negativity, complete responses, event-free survival, and overall survival, reported Sara Ghorashian, MD from the University College London Great Ormond Street Institute of Child Health, on behalf of the International BFM Resistant Disease Committee.
“The disease-related outcomes noted in this cohort of younger children predominantly with relapsed/refractory infant [mixed lineage leukemia]–rearranged ALL were at least as good as for the ELIANA study,” she said in an oral abstract presented during the European Hematology Association annual congress (Abstract S116).
The international, single-arm, open-label, ELIANA study was a phase 2 trial that included 97 patients aged 3-24 years with relapsed or refractory B-cell ALL, most of whom had previously undergone a hematopoietic stem cell transplant. Of those patients, 79 patients went on to receive a single infusion of the CAR T therapy.
“It’s fantastic data,” said Kevin J. Curran, MD, a pediatric hematologist/oncologist specializing in stem cell transplants and cellular therapy at Memorial Sloan Kettering Cancer Center, New York.
“Pediatric leukemia, while it’s the most common malignancy that happens in children, when you get down to this really small group, this under 3-year-old group, it’s hard to get a cohort, and for them to put together 30 patients, and show these great results is groundbreaking,” he said in an interview.
“Most importantly, it gives hope to parents who have young children who have really difficult to treat leukemia,” he said.
Dr. Curran was not involved in the study.
Scarce data on ALL in infants
“Children under 3 years of age were excluded from the ELIANA study, yet in terms of having often highly aggressive disease, with traditionally poor outcomes with conventional therapy, the need for novel forms of therapy for children with relapsed infant ALL is important,” Dr. Ghorashian said.
Because there is a paucity of data on outcomes in the youngest children, some health authorities will not support the use of tisagenlecleucel in this age group, and there are concerns about difficulties with performing leukapheresis in children weighing less than 10 kg, she noted.
To gain a better understanding of outcomes, members of the International BFM (Berlin-Frankfurt-Munster) Study Group conducted a retrospective analysis of data on all patients assessed for tisagenlecleucel for B-ALL who were aged under 3 years at screening at 1 of 15 centers in Europe and Israel.
A total of 30 patients were screened and had T cells harvested. Of this group, three patients did not receive CAR T infusions, two because of manufacturing failures, and one because of progressive disease.
Of the 27 patients who received CAR T infusions, 26 were evaluable for disease outcomes (1 had yet to reach the 30-day post infusion at the time of data cutoff).
The median age at diagnosis was 4.4 months, and the median age at infusion was 17.4 months; 19 of the 30 children in the entire cohort were boys. Mixed lineage leukemia rearrangements were found in 24 children, and 21 had undergone a stem cell transplant.
The children had a median of two prior lines of therapy, not including transplant. Seven of the children had received inotuzumab (Besponsa) and 11 had received blinotumumab (Blincyto).
High success rate
Of the 27 patients infused, 17 had sufficient cells harvested in a single day, and the remainder required 2-4 days. As noted, the CAR T product was successfully manufactured in 28 patients, with a median dose of 2.3 x 106/kg of patient weight.
The treatment failed for 2 of the 26 efficacy-evaluable patients, resulting in an MRD-negative rate of 92%.
Event-free survival at 6 months was 67%, similar to that in ELIANA (73%), and the 12-month event-free survival was 58%, which was superior to that in ELIANA (50%).
The 6-month and 12-month overall survival rates among the younger children were identical at 88%, compared with 90% and 76%, respectively, in ELIANA.
The 6- and 12-month probability of ongoing B-cell depletion, indicating CAR T persistence, were 77% and 68%, respectively. In ELIANA, the 6-month probability of B-cell depletion was 83%.
A total of 10 of the 27 patients received further therapy, including 3 who were given maintenance therapy for poor CAR T persistence, 2 who underwent chemotherapy for relapse, and 5 who underwent allogeneic stem cell transplant.
Of six patients who experienced a relapse after having a complete response, two had CD19 relapse.
Low rate of serious CRS
At 30 days post infusion, grade 3 or greater cytokine release syndrome (CRS) had occurred in two patients, severe neurotoxicity occurred in one, and grade 3 or greater prolonged cytopenias occurred in eight patients.
The toxicity profile in this study was generally favorable in comparison with ELIANA, with shorter median duration of CRS, shorter median duration of CRS-related ICU stay, and a lower frequency of tocilizumab use. It should be noted, however, that the I-BFM investigators used American Society for Transplantation and Cellular Therapy CRS consenus criteria, whereas the ELIANA investigators used University of Pennsylvania criteria.
“If the longer-term follow-up data are encouraging, it might suggest that the outcomes from tisagenlecleucel therapy are comparable to that of stem cell transplantation in high-risk relapsed infant ALL, without the associated late effects, and possibly supports CAR T-cell therapy eventually replace stem cell transplantation in this setting,” Dr. Ghorashian said.
Dr. Curran, who leads the CAR T effort at MSK Kids, the children’s division of MSKCC, agreed that the goal is for CAR T to replace stem cell transplants.
“I hope I put my clinical practice out of business with my research practice,” he said, but added that “I think we need to do more research in figuring out how to best use CAR T cells, either earlier, or as some data suggest, by treating patients with lower disease burden we would get better durability.
“Because obviously in kids’ cancer one relapse is too much, and we want to be able to raise that bar and provide hope and a cure for all of our children,” he said.
The study was sponsored by the I-BFM Resistant Disease Committee and member institutions. Dr. Ghorashian disclosed advisory board activity for Novartis, maker of tisagenlecleucel, and patents and royalties from UCL Business. Dr. Curran research funding and consulting fees from Novartis.
FROM EHA 2021