TBD Meeting (3270-20)

Patients with hematologic disease who develop COVID-19 may experience substantial morbidity and mortality related to SARS-CoV-2 infection, according to recent registry data reported at the all-virtual annual meeting of the American Society of Hematology.

Overall mortality was 28% for the first 250 patients entered into the ASH Research Collaborative COVID-19 Registry for Hematology, researchers reported in an abstract of their study findings.

However, the burden of death and moderate-to-severe COVID-19 outcomes was highest in patients with poorer prognosis and those with relapsed/refractory hematological disease, they added.

The most commonly represented malignancies were acute leukemia, non-Hodgkin lymphoma, and myeloma or amyloidosis, according to the report.

Taken together, the findings do support an “emerging consensus” that COVID-19 related morbidity and mortality is significant in these patients, authors said – however, the current findings may not be reason enough to support a change in treatment course for the underlying disease.

“We see no reason, based on our data, to withhold intensive therapies from patients with underlying hematologic malignancies and favorable prognoses, if aggressive supportive care is consistent with patient preferences,” wrote the researchers.

ASH President Stephanie Lee, MD, MPH, said these registry findings are important to better understand how SARS-CoV-2 is affecting not only patients with hematologic diseases, but also individuals who experience COVID-19-related hematologic complications.

However, the findings are limited due to the heterogeneity of diseases, symptoms, and treatments represented in the registry, said Dr. Lee, associate director of the clinical research division at Fred Hutchinson Cancer Center in Seattle.

“More data will be coming in, but I think this is an example of trying to harness real-world information to try to learn things until we get more controlled studies,” Dr. Lee said in a media briefing held in advance of the ASH meeting.
 

Comorbidities and more

Patients with blood cancers are often older and may have comorbidities such as diabetes or hypertension that have been linked to poor COVID-19 outcomes, according to the authors of the report, led by William A. Wood, MD, MPH, associate professor of medicine with the UNC Lineberger Comprehensive Cancer Center in Chapel Hill, N.C.

Moreover, these patients may have underlying immune dysfunction and may receive chemotherapy or immunotherapy that is “profoundly immunosuppressive,” Dr. Wood and coauthors said in their report.

To date, however, risks of morbidity and mortality related to SARS-CoV-2 infection have not been well defined in this patient population, authors said.

More data is emerging now from the ASH Research Collaborative COVID-19 Registry for Hematology, which includes data on patients positive for COVID-19 who have a past or present hematologic condition or have experienced a hematologic complication related to COVID-19.

All data from the registry is being made available through a dashboard on the ASH Research Collaborative website, which as of Dec. 1, 2020, included 693 complete cases.

The data cut in the ASH abstract includes the first 250 patients enrolled at 74 sites around the world, the authors said. The most common malignancies included acute leukemia in 33%, non-Hodgkin lymphoma in 27%, and myeloma or amyloidosis in 16%.

The most frequently reported symptoms included fever in 73%, cough in 67%, dyspnea in 50%, and fatigue in 40%, according to that report.

At the time of this data snapshot, treatment with COVID-19-directed therapies including hydroxychloroquine or azithromycin were common, reported in 76 and 59 patients, respectively, in the cohort.

Batch submissions from sites with high incidence of COVID-19 infection are ongoing. The registry has been expanded to include nonmalignant hematologic diseases, and the registry will continue to accumulate data as a resource for the hematology community.

Overall mortality was 28% at the time, according to the abstract, with nearly all of the deaths occurring in patients classified as having COVID-19 that was moderate (i.e., requiring hospitalization) or severe (i.e., requiring ICU admission).

“In some instances, death occurred after a decision was made to forgo ICU admission in favor of a palliative approach,” said Dr. Wood and coauthors in their report.

Dr. Wood reported research funding from Pfizer, consultancy with Teladoc/Best Doctors, and honoraria from the ASH Research Collaborative. Coauthors provided disclosures related to Celgene, Madrigal Pharmaceuticals, Pharmacyclics, and Amgen, among others.

SOURCE: Wood WA et al. ASH 2020, Abstract 215.

Patients with hematologic disease who develop COVID-19 may experience substantial morbidity and mortality related to SARS-CoV-2 infection, according to recent registry data reported at the all-virtual annual meeting of the American Society of Hematology.

Overall mortality was 28% for the first 250 patients entered into the ASH Research Collaborative COVID-19 Registry for Hematology, researchers reported in an abstract of their study findings.

However, the burden of death and moderate-to-severe COVID-19 outcomes was highest in patients with poorer prognosis and those with relapsed/refractory hematological disease, they added.

The most commonly represented malignancies were acute leukemia, non-Hodgkin lymphoma, and myeloma or amyloidosis, according to the report.

Taken together, the findings do support an “emerging consensus” that COVID-19 related morbidity and mortality is significant in these patients, authors said – however, the current findings may not be reason enough to support a change in treatment course for the underlying disease.

“We see no reason, based on our data, to withhold intensive therapies from patients with underlying hematologic malignancies and favorable prognoses, if aggressive supportive care is consistent with patient preferences,” wrote the researchers.

ASH President Stephanie Lee, MD, MPH, said these registry findings are important to better understand how SARS-CoV-2 is affecting not only patients with hematologic diseases, but also individuals who experience COVID-19-related hematologic complications.

However, the findings are limited due to the heterogeneity of diseases, symptoms, and treatments represented in the registry, said Dr. Lee, associate director of the clinical research division at Fred Hutchinson Cancer Center in Seattle.

“More data will be coming in, but I think this is an example of trying to harness real-world information to try to learn things until we get more controlled studies,” Dr. Lee said in a media briefing held in advance of the ASH meeting.
 

Comorbidities and more

Patients with blood cancers are often older and may have comorbidities such as diabetes or hypertension that have been linked to poor COVID-19 outcomes, according to the authors of the report, led by William A. Wood, MD, MPH, associate professor of medicine with the UNC Lineberger Comprehensive Cancer Center in Chapel Hill, N.C.

Moreover, these patients may have underlying immune dysfunction and may receive chemotherapy or immunotherapy that is “profoundly immunosuppressive,” Dr. Wood and coauthors said in their report.

To date, however, risks of morbidity and mortality related to SARS-CoV-2 infection have not been well defined in this patient population, authors said.

More data is emerging now from the ASH Research Collaborative COVID-19 Registry for Hematology, which includes data on patients positive for COVID-19 who have a past or present hematologic condition or have experienced a hematologic complication related to COVID-19.

All data from the registry is being made available through a dashboard on the ASH Research Collaborative website, which as of Dec. 1, 2020, included 693 complete cases.

The data cut in the ASH abstract includes the first 250 patients enrolled at 74 sites around the world, the authors said. The most common malignancies included acute leukemia in 33%, non-Hodgkin lymphoma in 27%, and myeloma or amyloidosis in 16%.

The most frequently reported symptoms included fever in 73%, cough in 67%, dyspnea in 50%, and fatigue in 40%, according to that report.

At the time of this data snapshot, treatment with COVID-19-directed therapies including hydroxychloroquine or azithromycin were common, reported in 76 and 59 patients, respectively, in the cohort.

Batch submissions from sites with high incidence of COVID-19 infection are ongoing. The registry has been expanded to include nonmalignant hematologic diseases, and the registry will continue to accumulate data as a resource for the hematology community.

Overall mortality was 28% at the time, according to the abstract, with nearly all of the deaths occurring in patients classified as having COVID-19 that was moderate (i.e., requiring hospitalization) or severe (i.e., requiring ICU admission).

“In some instances, death occurred after a decision was made to forgo ICU admission in favor of a palliative approach,” said Dr. Wood and coauthors in their report.

Dr. Wood reported research funding from Pfizer, consultancy with Teladoc/Best Doctors, and honoraria from the ASH Research Collaborative. Coauthors provided disclosures related to Celgene, Madrigal Pharmaceuticals, Pharmacyclics, and Amgen, among others.

SOURCE: Wood WA et al. ASH 2020, Abstract 215.

Patients with hematologic disease who develop COVID-19 may experience substantial morbidity and mortality related to SARS-CoV-2 infection, according to recent registry data reported at the all-virtual annual meeting of the American Society of Hematology.

Overall mortality was 28% for the first 250 patients entered into the ASH Research Collaborative COVID-19 Registry for Hematology, researchers reported in an abstract of their study findings.

However, the burden of death and moderate-to-severe COVID-19 outcomes was highest in patients with poorer prognosis and those with relapsed/refractory hematological disease, they added.

The most commonly represented malignancies were acute leukemia, non-Hodgkin lymphoma, and myeloma or amyloidosis, according to the report.

Taken together, the findings do support an “emerging consensus” that COVID-19 related morbidity and mortality is significant in these patients, authors said – however, the current findings may not be reason enough to support a change in treatment course for the underlying disease.

“We see no reason, based on our data, to withhold intensive therapies from patients with underlying hematologic malignancies and favorable prognoses, if aggressive supportive care is consistent with patient preferences,” wrote the researchers.

ASH President Stephanie Lee, MD, MPH, said these registry findings are important to better understand how SARS-CoV-2 is affecting not only patients with hematologic diseases, but also individuals who experience COVID-19-related hematologic complications.

However, the findings are limited due to the heterogeneity of diseases, symptoms, and treatments represented in the registry, said Dr. Lee, associate director of the clinical research division at Fred Hutchinson Cancer Center in Seattle.

“More data will be coming in, but I think this is an example of trying to harness real-world information to try to learn things until we get more controlled studies,” Dr. Lee said in a media briefing held in advance of the ASH meeting.
 

Comorbidities and more

Patients with blood cancers are often older and may have comorbidities such as diabetes or hypertension that have been linked to poor COVID-19 outcomes, according to the authors of the report, led by William A. Wood, MD, MPH, associate professor of medicine with the UNC Lineberger Comprehensive Cancer Center in Chapel Hill, N.C.

Moreover, these patients may have underlying immune dysfunction and may receive chemotherapy or immunotherapy that is “profoundly immunosuppressive,” Dr. Wood and coauthors said in their report.

To date, however, risks of morbidity and mortality related to SARS-CoV-2 infection have not been well defined in this patient population, authors said.

More data is emerging now from the ASH Research Collaborative COVID-19 Registry for Hematology, which includes data on patients positive for COVID-19 who have a past or present hematologic condition or have experienced a hematologic complication related to COVID-19.

All data from the registry is being made available through a dashboard on the ASH Research Collaborative website, which as of Dec. 1, 2020, included 693 complete cases.

The data cut in the ASH abstract includes the first 250 patients enrolled at 74 sites around the world, the authors said. The most common malignancies included acute leukemia in 33%, non-Hodgkin lymphoma in 27%, and myeloma or amyloidosis in 16%.

The most frequently reported symptoms included fever in 73%, cough in 67%, dyspnea in 50%, and fatigue in 40%, according to that report.

At the time of this data snapshot, treatment with COVID-19-directed therapies including hydroxychloroquine or azithromycin were common, reported in 76 and 59 patients, respectively, in the cohort.

Batch submissions from sites with high incidence of COVID-19 infection are ongoing. The registry has been expanded to include nonmalignant hematologic diseases, and the registry will continue to accumulate data as a resource for the hematology community.

Overall mortality was 28% at the time, according to the abstract, with nearly all of the deaths occurring in patients classified as having COVID-19 that was moderate (i.e., requiring hospitalization) or severe (i.e., requiring ICU admission).

“In some instances, death occurred after a decision was made to forgo ICU admission in favor of a palliative approach,” said Dr. Wood and coauthors in their report.

Dr. Wood reported research funding from Pfizer, consultancy with Teladoc/Best Doctors, and honoraria from the ASH Research Collaborative. Coauthors provided disclosures related to Celgene, Madrigal Pharmaceuticals, Pharmacyclics, and Amgen, among others.

SOURCE: Wood WA et al. ASH 2020, Abstract 215.

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

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

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

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

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

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

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

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

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

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

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

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

Immediate impact on clinical practice

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

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

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

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

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

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

Reimbursement by CMS for Medicare recipients

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

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

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

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

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

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

BMT CTN 1102 study details

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

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

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

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

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

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

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

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

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

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

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

Role for alternate donors

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Immediate impact on clinical practice

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

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

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

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

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

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

Reimbursement by CMS for Medicare recipients

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

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

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

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

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

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

BMT CTN 1102 study details

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

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

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

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

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

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

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

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

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

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

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

Role for alternate donors

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Immediate impact on clinical practice

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

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

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

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

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

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

Reimbursement by CMS for Medicare recipients

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

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

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

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

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

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

BMT CTN 1102 study details

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

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

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

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

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

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

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

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

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

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

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

Role for alternate donors

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

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

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

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

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

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

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

Instead of flying out to San Diego in California and soaking up a bit of sunshine in between listening to new research presentations, hematologists from around the world will be glued to their computer screens next weekend, tuning into the 62nd American Society of Hematology annual meeting.  

Like many other conferences this year, the ASH meeting will be virtual because of the continuing COVID-19 pandemic, although the dates remain the same: Dec. 5-8.  

This is the premier hematology event of the year, and the largest hematology conference in the world, with around 3,500 abstracts presented this year, commented Aaron T. Gerds, MD, chair of ASH’s Committee on Communications.
 

Ruxolitinib in chronic GvHD

“One of the things that people come to ASH for is to hear about practice-changing clinical trials, and this year is no exception,” said ASH secretary Robert Brodsky, MD.

In a preview webinar, he highlighted four abstracts that offer opportunities to change practice and revamp the current standards of care.

One clinical trial that is “almost certainly a practice changer,” he said, is the REACH 3 study (abstract 77) of the JAK inhibitor ruxolitinib (Jakafi, Incyte) in patients with chronic graft-versus-host disease (GvHD) after a stem cell transplant.

“This has been really hard to treat in patients undergoing allogeneic bone marrow transplants,” said Brodsky. “Steroids are the first-line treatment, but after that, nothing else has shown any improvement, and even steroids don’t work that well.”

There is currently no approved second-line therapy for chronic forms of GvHD, he emphasized. The main endpoint of the trial was overall response rate, which was doubled with ruxolitinib compared to the best available therapy (50% vs 25%).

“This is the first successful phase 3 trial for chronic GvHD,” Brodsky commented.  
 

Transplants for older patients with MDS

Transplant offers the only curative option for myelodysplastic syndromes (MDS), but typically this option is offered to younger patients because benefits for older adults have not been well-defined, Brodsky noted.

New data from a clinical trial conducted in patients with advanced MDS aged 50-75 years (abstract 75) offers the most definitive evidence to date that allogeneic hematopoietic cell transplantation (AHCT) can significantly improve outcomes for older adults.  

It’s clear that transplant is the standard of care in younger patients, Brodsky commented, and although there is a trend of offering it to older patients, some are not getting referred and instead are being offered palliative care. “The thinking is that bone marrow transplant would be too toxic in this age group,” he said. “But what is very clear here is that, in an intent-to-treat analysis, there was a significant survival advantage – 48% versus 27% at 3 years for transplantation – and it was seen across all subgroups.”
 

Subcutaneous daratumumab

New data on a subcutaneous formulation of daratumumab (Darzalex, Janssen), which is usually given by intravenous infusion, will be presented from the APOLLO trial (abstract 412) in patients with relapsed/refractory multiple myeloma.

Patients who received subcutaneous daratumumab combined with pomalidomide and dexamethasone had a 37% reduction in disease progression or death compared to those who received pomalidomide and dexamethasone alone.

“From previous years we’ve learned that daratumumab has had a major impact on outcomes in multiple myeloma,” said Brodsky. “The nice thing about the subcutaneous formulation is that it can be administered quickly and in an outpatient setting, which is especially important in the COVID era.”  
 

Negative data with tranexamic acid

The fourth abstract highlighted by Brodsky is a negative study, but its findings can help guide clinical practice, he said. The a-TREAT study (abstract 2) showed that, despite being routinely used in the clinical setting, tranexamic acid does not prevent bleeding when administered prophylactically to severely thrombocytopenic patients undergoing treatment for hematologic malignancies.

“They found absolutely no difference in bleeding or need for transfusion,” said Brodsky. “What they did find was more catheter-associated blood clots in the tranexamic acid group. This is a practice changer in that it probably should not be given prophylactically to patients with thrombocytopenia.”
 

‘Very exciting’ news about gene therapy

Brodsky also highlighted several late-breaking abstract that will be presented at the meeting.

In particular, the first data on a gene therapy for hemophilia B (abstract LBA-6) are “very, very exciting,” he said. The HOPE-B trial showed a 96% response rate among patients with hemophilia B who were treated with etranacogene dezaparvovec, an investigational gene therapy composed of an adeno-associated virus serotype 5 (AAV5) vector containing a codon-optimized Padua variant human factor IX.

Brodsky pointed out that this was a large trial with 54 patients, but importantly, it included patients with pre-existing anti-AAV5 neutralizing antibodies. “About 40% of patients have naturally occurring antibodies to AAV5, and they have been excluded from previous trials because it was thought they wouldn’t take the vector,” said Brodsky. “But only one patient didn’t get a response.”

Following a single dose of etranacogene dezaparvovec, Factor IX activity increased into the mild to normal range without the need for prophylactic immunosuppression. Treated patients were able to discontinue prophylaxis and bleeding was controlled in most of the cohort.

“This is a big advance and we are getting very close to the point where gene therapy is going to be standard of care for some forms of hemophilia,” said Brodsky. However, he added that “we will still need to see more patients and have longer follow-up.”

He added that, with time, the technology behind gene therapy will probably become less expensive and more accessible to more patients, which will help become a standard of care.

This is also the hope for the technology behind chimeric antigen receptor T-cell (CAR-T) therapy, he added. At present, this cellular therapy is manufactured individually for each patient and is very expensive, but work on “off-the-shelf” products is underway. This topic will be explored during the presidential symposium, entitled, “Universal Donor Solutions in Hematology.”

New data on one of the currently available CAR-T cell products will be presented at the meeting. The phase 2 ZUMA-5 trial showed that axicabtagene ciloleucel (Axi-Cel) may be a viable option for some patients with high-risk non-Hodgkin lymphoma who have not responded to standard treatments (abstract 700).

At a median follow-up of almost 18 months, 92% of participants achieved an objective response, and 78% achieved a complete response to the treatment. By 12 months, 72% were still in response, and at 17.5 months, 64% were still in response.

“We were very impressed with the magnitude of the responses, and also the durability,” said senior study author Caron Jacobson, MD, of the Dana-Farber Cancer Institute, Boston, in a press release. “I was also struck early on by how favorable the safety profile was compared to what we’ve been seeing in the fast-growing lymphomas, such as large B cell lymphoma.”
 

Race and bloods cancers

ASH president Stephanie Lee, MD, MPH, highlighted several abstracts on disparities that will be presented at the meeting. One of these, which is to be presented during the plenary session, is an analysis of patient survival in acute myeloid leukemia (AML) (abstract 6).

It found that “self-reported race was the best indicator of survival,” noted Lee.

Overall survival at 3 years was 41% in White patients versus 32% in Black patients, a difference that was highly significant, she noted.

Part of the study also evaluated patients who were all on the same chemotherapy protocol, “so there was no effect of different treatment since they were on therapy determined by the trial,” said Lee.

Black patients were less likely to have normal cytogenetics compared with White patients (38% vs 51%; P = .01) and had a lower frequency of prognostically favorable NPM1 mutations (25% vs 38%; P = .04), but higher frequencies of spliceosome gene mutations (24% vs 12%; P = .009). Therefore, the results showed race was an independent prognosticator of poor survival in AML, aside from established molecular markers.

A special scientific session on race will be held on Dec. 5, Lee noted. While other abstracts consider race from the patient side, this session will focus on the scientist’s side, she explained, and address questions such as: “What are the implications of diversity and racism? And how does that impact scientists who are from underrepresented minorities?” 
 

COVID-19 and blood disorders

Lee also highlighted a study (abstract 215) that analyzed emerging data from the ASH Research Collaborative COVID-19 Registry for Hematology, which was developed to look at outcomes of COVID-19 infection in patients with underlying blood disorders.

An analysis of data from 250 patients at 74 sites around the world found that overall mortality was 28%. “This supports the emerging consensus that patients with hematologic malignancies experience significant morbidity and mortality from COVID-19 infection,” say the authors.

“We do need real-world data to see how SARS-CoV-2 is affecting our patients with hematologic diseases or those who don’t have a hematologic disease but who are then infected with the coronavirus and develop a hematologic problem like blood clots,” said Lee.

“More data will be coming in, but this is a good example of trying to harness real-world information to learn things until we have more controlled trials.”
 

‘Fireside chat’ with Fauci

COVID-19 will be on the agenda for a special session billed as a “fireside chat” with Anthony Fauci, MD, of the National Institute of Allergy and Infectious Diseases, National Institutes of Health.

“This will be kicking off our meeting on Saturday morning,” said Lee.

This article first appeared on Medscape.com.

Instead of flying out to San Diego in California and soaking up a bit of sunshine in between listening to new research presentations, hematologists from around the world will be glued to their computer screens next weekend, tuning into the 62nd American Society of Hematology annual meeting.  

Like many other conferences this year, the ASH meeting will be virtual because of the continuing COVID-19 pandemic, although the dates remain the same: Dec. 5-8.  

This is the premier hematology event of the year, and the largest hematology conference in the world, with around 3,500 abstracts presented this year, commented Aaron T. Gerds, MD, chair of ASH’s Committee on Communications.
 

Ruxolitinib in chronic GvHD

“One of the things that people come to ASH for is to hear about practice-changing clinical trials, and this year is no exception,” said ASH secretary Robert Brodsky, MD.

In a preview webinar, he highlighted four abstracts that offer opportunities to change practice and revamp the current standards of care.

One clinical trial that is “almost certainly a practice changer,” he said, is the REACH 3 study (abstract 77) of the JAK inhibitor ruxolitinib (Jakafi, Incyte) in patients with chronic graft-versus-host disease (GvHD) after a stem cell transplant.

“This has been really hard to treat in patients undergoing allogeneic bone marrow transplants,” said Brodsky. “Steroids are the first-line treatment, but after that, nothing else has shown any improvement, and even steroids don’t work that well.”

There is currently no approved second-line therapy for chronic forms of GvHD, he emphasized. The main endpoint of the trial was overall response rate, which was doubled with ruxolitinib compared to the best available therapy (50% vs 25%).

“This is the first successful phase 3 trial for chronic GvHD,” Brodsky commented.  
 

Transplants for older patients with MDS

Transplant offers the only curative option for myelodysplastic syndromes (MDS), but typically this option is offered to younger patients because benefits for older adults have not been well-defined, Brodsky noted.

New data from a clinical trial conducted in patients with advanced MDS aged 50-75 years (abstract 75) offers the most definitive evidence to date that allogeneic hematopoietic cell transplantation (AHCT) can significantly improve outcomes for older adults.  

It’s clear that transplant is the standard of care in younger patients, Brodsky commented, and although there is a trend of offering it to older patients, some are not getting referred and instead are being offered palliative care. “The thinking is that bone marrow transplant would be too toxic in this age group,” he said. “But what is very clear here is that, in an intent-to-treat analysis, there was a significant survival advantage – 48% versus 27% at 3 years for transplantation – and it was seen across all subgroups.”
 

Subcutaneous daratumumab

New data on a subcutaneous formulation of daratumumab (Darzalex, Janssen), which is usually given by intravenous infusion, will be presented from the APOLLO trial (abstract 412) in patients with relapsed/refractory multiple myeloma.

Patients who received subcutaneous daratumumab combined with pomalidomide and dexamethasone had a 37% reduction in disease progression or death compared to those who received pomalidomide and dexamethasone alone.

“From previous years we’ve learned that daratumumab has had a major impact on outcomes in multiple myeloma,” said Brodsky. “The nice thing about the subcutaneous formulation is that it can be administered quickly and in an outpatient setting, which is especially important in the COVID era.”  
 

Negative data with tranexamic acid

The fourth abstract highlighted by Brodsky is a negative study, but its findings can help guide clinical practice, he said. The a-TREAT study (abstract 2) showed that, despite being routinely used in the clinical setting, tranexamic acid does not prevent bleeding when administered prophylactically to severely thrombocytopenic patients undergoing treatment for hematologic malignancies.

“They found absolutely no difference in bleeding or need for transfusion,” said Brodsky. “What they did find was more catheter-associated blood clots in the tranexamic acid group. This is a practice changer in that it probably should not be given prophylactically to patients with thrombocytopenia.”
 

‘Very exciting’ news about gene therapy

Brodsky also highlighted several late-breaking abstract that will be presented at the meeting.

In particular, the first data on a gene therapy for hemophilia B (abstract LBA-6) are “very, very exciting,” he said. The HOPE-B trial showed a 96% response rate among patients with hemophilia B who were treated with etranacogene dezaparvovec, an investigational gene therapy composed of an adeno-associated virus serotype 5 (AAV5) vector containing a codon-optimized Padua variant human factor IX.

Brodsky pointed out that this was a large trial with 54 patients, but importantly, it included patients with pre-existing anti-AAV5 neutralizing antibodies. “About 40% of patients have naturally occurring antibodies to AAV5, and they have been excluded from previous trials because it was thought they wouldn’t take the vector,” said Brodsky. “But only one patient didn’t get a response.”

Following a single dose of etranacogene dezaparvovec, Factor IX activity increased into the mild to normal range without the need for prophylactic immunosuppression. Treated patients were able to discontinue prophylaxis and bleeding was controlled in most of the cohort.

“This is a big advance and we are getting very close to the point where gene therapy is going to be standard of care for some forms of hemophilia,” said Brodsky. However, he added that “we will still need to see more patients and have longer follow-up.”

He added that, with time, the technology behind gene therapy will probably become less expensive and more accessible to more patients, which will help become a standard of care.

This is also the hope for the technology behind chimeric antigen receptor T-cell (CAR-T) therapy, he added. At present, this cellular therapy is manufactured individually for each patient and is very expensive, but work on “off-the-shelf” products is underway. This topic will be explored during the presidential symposium, entitled, “Universal Donor Solutions in Hematology.”

New data on one of the currently available CAR-T cell products will be presented at the meeting. The phase 2 ZUMA-5 trial showed that axicabtagene ciloleucel (Axi-Cel) may be a viable option for some patients with high-risk non-Hodgkin lymphoma who have not responded to standard treatments (abstract 700).

At a median follow-up of almost 18 months, 92% of participants achieved an objective response, and 78% achieved a complete response to the treatment. By 12 months, 72% were still in response, and at 17.5 months, 64% were still in response.

“We were very impressed with the magnitude of the responses, and also the durability,” said senior study author Caron Jacobson, MD, of the Dana-Farber Cancer Institute, Boston, in a press release. “I was also struck early on by how favorable the safety profile was compared to what we’ve been seeing in the fast-growing lymphomas, such as large B cell lymphoma.”
 

Race and bloods cancers

ASH president Stephanie Lee, MD, MPH, highlighted several abstracts on disparities that will be presented at the meeting. One of these, which is to be presented during the plenary session, is an analysis of patient survival in acute myeloid leukemia (AML) (abstract 6).

It found that “self-reported race was the best indicator of survival,” noted Lee.

Overall survival at 3 years was 41% in White patients versus 32% in Black patients, a difference that was highly significant, she noted.

Part of the study also evaluated patients who were all on the same chemotherapy protocol, “so there was no effect of different treatment since they were on therapy determined by the trial,” said Lee.

Black patients were less likely to have normal cytogenetics compared with White patients (38% vs 51%; P = .01) and had a lower frequency of prognostically favorable NPM1 mutations (25% vs 38%; P = .04), but higher frequencies of spliceosome gene mutations (24% vs 12%; P = .009). Therefore, the results showed race was an independent prognosticator of poor survival in AML, aside from established molecular markers.

A special scientific session on race will be held on Dec. 5, Lee noted. While other abstracts consider race from the patient side, this session will focus on the scientist’s side, she explained, and address questions such as: “What are the implications of diversity and racism? And how does that impact scientists who are from underrepresented minorities?” 
 

COVID-19 and blood disorders

Lee also highlighted a study (abstract 215) that analyzed emerging data from the ASH Research Collaborative COVID-19 Registry for Hematology, which was developed to look at outcomes of COVID-19 infection in patients with underlying blood disorders.

An analysis of data from 250 patients at 74 sites around the world found that overall mortality was 28%. “This supports the emerging consensus that patients with hematologic malignancies experience significant morbidity and mortality from COVID-19 infection,” say the authors.

“We do need real-world data to see how SARS-CoV-2 is affecting our patients with hematologic diseases or those who don’t have a hematologic disease but who are then infected with the coronavirus and develop a hematologic problem like blood clots,” said Lee.

“More data will be coming in, but this is a good example of trying to harness real-world information to learn things until we have more controlled trials.”
 

‘Fireside chat’ with Fauci

COVID-19 will be on the agenda for a special session billed as a “fireside chat” with Anthony Fauci, MD, of the National Institute of Allergy and Infectious Diseases, National Institutes of Health.

“This will be kicking off our meeting on Saturday morning,” said Lee.

This article first appeared on Medscape.com.

Instead of flying out to San Diego in California and soaking up a bit of sunshine in between listening to new research presentations, hematologists from around the world will be glued to their computer screens next weekend, tuning into the 62nd American Society of Hematology annual meeting.  

Like many other conferences this year, the ASH meeting will be virtual because of the continuing COVID-19 pandemic, although the dates remain the same: Dec. 5-8.  

This is the premier hematology event of the year, and the largest hematology conference in the world, with around 3,500 abstracts presented this year, commented Aaron T. Gerds, MD, chair of ASH’s Committee on Communications.
 

Ruxolitinib in chronic GvHD

“One of the things that people come to ASH for is to hear about practice-changing clinical trials, and this year is no exception,” said ASH secretary Robert Brodsky, MD.

In a preview webinar, he highlighted four abstracts that offer opportunities to change practice and revamp the current standards of care.

One clinical trial that is “almost certainly a practice changer,” he said, is the REACH 3 study (abstract 77) of the JAK inhibitor ruxolitinib (Jakafi, Incyte) in patients with chronic graft-versus-host disease (GvHD) after a stem cell transplant.

“This has been really hard to treat in patients undergoing allogeneic bone marrow transplants,” said Brodsky. “Steroids are the first-line treatment, but after that, nothing else has shown any improvement, and even steroids don’t work that well.”

There is currently no approved second-line therapy for chronic forms of GvHD, he emphasized. The main endpoint of the trial was overall response rate, which was doubled with ruxolitinib compared to the best available therapy (50% vs 25%).

“This is the first successful phase 3 trial for chronic GvHD,” Brodsky commented.  
 

Transplants for older patients with MDS

Transplant offers the only curative option for myelodysplastic syndromes (MDS), but typically this option is offered to younger patients because benefits for older adults have not been well-defined, Brodsky noted.

New data from a clinical trial conducted in patients with advanced MDS aged 50-75 years (abstract 75) offers the most definitive evidence to date that allogeneic hematopoietic cell transplantation (AHCT) can significantly improve outcomes for older adults.  

It’s clear that transplant is the standard of care in younger patients, Brodsky commented, and although there is a trend of offering it to older patients, some are not getting referred and instead are being offered palliative care. “The thinking is that bone marrow transplant would be too toxic in this age group,” he said. “But what is very clear here is that, in an intent-to-treat analysis, there was a significant survival advantage – 48% versus 27% at 3 years for transplantation – and it was seen across all subgroups.”
 

Subcutaneous daratumumab

New data on a subcutaneous formulation of daratumumab (Darzalex, Janssen), which is usually given by intravenous infusion, will be presented from the APOLLO trial (abstract 412) in patients with relapsed/refractory multiple myeloma.

Patients who received subcutaneous daratumumab combined with pomalidomide and dexamethasone had a 37% reduction in disease progression or death compared to those who received pomalidomide and dexamethasone alone.

“From previous years we’ve learned that daratumumab has had a major impact on outcomes in multiple myeloma,” said Brodsky. “The nice thing about the subcutaneous formulation is that it can be administered quickly and in an outpatient setting, which is especially important in the COVID era.”  
 

Negative data with tranexamic acid

The fourth abstract highlighted by Brodsky is a negative study, but its findings can help guide clinical practice, he said. The a-TREAT study (abstract 2) showed that, despite being routinely used in the clinical setting, tranexamic acid does not prevent bleeding when administered prophylactically to severely thrombocytopenic patients undergoing treatment for hematologic malignancies.

“They found absolutely no difference in bleeding or need for transfusion,” said Brodsky. “What they did find was more catheter-associated blood clots in the tranexamic acid group. This is a practice changer in that it probably should not be given prophylactically to patients with thrombocytopenia.”
 

‘Very exciting’ news about gene therapy

Brodsky also highlighted several late-breaking abstract that will be presented at the meeting.

In particular, the first data on a gene therapy for hemophilia B (abstract LBA-6) are “very, very exciting,” he said. The HOPE-B trial showed a 96% response rate among patients with hemophilia B who were treated with etranacogene dezaparvovec, an investigational gene therapy composed of an adeno-associated virus serotype 5 (AAV5) vector containing a codon-optimized Padua variant human factor IX.

Brodsky pointed out that this was a large trial with 54 patients, but importantly, it included patients with pre-existing anti-AAV5 neutralizing antibodies. “About 40% of patients have naturally occurring antibodies to AAV5, and they have been excluded from previous trials because it was thought they wouldn’t take the vector,” said Brodsky. “But only one patient didn’t get a response.”

Following a single dose of etranacogene dezaparvovec, Factor IX activity increased into the mild to normal range without the need for prophylactic immunosuppression. Treated patients were able to discontinue prophylaxis and bleeding was controlled in most of the cohort.

“This is a big advance and we are getting very close to the point where gene therapy is going to be standard of care for some forms of hemophilia,” said Brodsky. However, he added that “we will still need to see more patients and have longer follow-up.”

He added that, with time, the technology behind gene therapy will probably become less expensive and more accessible to more patients, which will help become a standard of care.

This is also the hope for the technology behind chimeric antigen receptor T-cell (CAR-T) therapy, he added. At present, this cellular therapy is manufactured individually for each patient and is very expensive, but work on “off-the-shelf” products is underway. This topic will be explored during the presidential symposium, entitled, “Universal Donor Solutions in Hematology.”

New data on one of the currently available CAR-T cell products will be presented at the meeting. The phase 2 ZUMA-5 trial showed that axicabtagene ciloleucel (Axi-Cel) may be a viable option for some patients with high-risk non-Hodgkin lymphoma who have not responded to standard treatments (abstract 700).

At a median follow-up of almost 18 months, 92% of participants achieved an objective response, and 78% achieved a complete response to the treatment. By 12 months, 72% were still in response, and at 17.5 months, 64% were still in response.

“We were very impressed with the magnitude of the responses, and also the durability,” said senior study author Caron Jacobson, MD, of the Dana-Farber Cancer Institute, Boston, in a press release. “I was also struck early on by how favorable the safety profile was compared to what we’ve been seeing in the fast-growing lymphomas, such as large B cell lymphoma.”
 

Race and bloods cancers

ASH president Stephanie Lee, MD, MPH, highlighted several abstracts on disparities that will be presented at the meeting. One of these, which is to be presented during the plenary session, is an analysis of patient survival in acute myeloid leukemia (AML) (abstract 6).

It found that “self-reported race was the best indicator of survival,” noted Lee.

Overall survival at 3 years was 41% in White patients versus 32% in Black patients, a difference that was highly significant, she noted.

Part of the study also evaluated patients who were all on the same chemotherapy protocol, “so there was no effect of different treatment since they were on therapy determined by the trial,” said Lee.

Black patients were less likely to have normal cytogenetics compared with White patients (38% vs 51%; P = .01) and had a lower frequency of prognostically favorable NPM1 mutations (25% vs 38%; P = .04), but higher frequencies of spliceosome gene mutations (24% vs 12%; P = .009). Therefore, the results showed race was an independent prognosticator of poor survival in AML, aside from established molecular markers.

A special scientific session on race will be held on Dec. 5, Lee noted. While other abstracts consider race from the patient side, this session will focus on the scientist’s side, she explained, and address questions such as: “What are the implications of diversity and racism? And how does that impact scientists who are from underrepresented minorities?” 
 

COVID-19 and blood disorders

Lee also highlighted a study (abstract 215) that analyzed emerging data from the ASH Research Collaborative COVID-19 Registry for Hematology, which was developed to look at outcomes of COVID-19 infection in patients with underlying blood disorders.

An analysis of data from 250 patients at 74 sites around the world found that overall mortality was 28%. “This supports the emerging consensus that patients with hematologic malignancies experience significant morbidity and mortality from COVID-19 infection,” say the authors.

“We do need real-world data to see how SARS-CoV-2 is affecting our patients with hematologic diseases or those who don’t have a hematologic disease but who are then infected with the coronavirus and develop a hematologic problem like blood clots,” said Lee.

“More data will be coming in, but this is a good example of trying to harness real-world information to learn things until we have more controlled trials.”
 

‘Fireside chat’ with Fauci

COVID-19 will be on the agenda for a special session billed as a “fireside chat” with Anthony Fauci, MD, of the National Institute of Allergy and Infectious Diseases, National Institutes of Health.

“This will be kicking off our meeting on Saturday morning,” said Lee.

This article first appeared on Medscape.com.