AVAHO

SAN DIEGO – Chimeric antigen receptor T-cell therapy with tisagenlecleucel (Kymriah) is associated with a high rate of durable responses in adults with relapsed or refractory diffuse large B-cell lymphoma, an updated analysis of the JULIET trial showed.

Neil Osterweil/MDedge News

After a median follow-up of 19 months, two-thirds of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who had early responses to chimeric antigen receptor (CAR) T-cell therapy with tisagenlecleucel remained in remission with no evidence of minimal residual disease, reported Richard Thomas Maziarz, MD, from the Oregon Health & Science Knight Cancer Institute in Portland, at the annual meeting of the American Society of Hematology.

“Since the previous report, no new deaths have been reported due to any cause other than patient disease progression. No treatment-related mortality was seen throughout the study, and there were three early deaths, all related to lymphoma that progressed,” he said in a briefing prior to presentation of the data in a scientific poster.

The updated study results were published simultaneously online in the New England Journal of Medicine.

JULIET then

In the phase 2, single-arm trial, investigators enrolled adults with DLBCL that had relapsed or was refractory after two or more prior lines of therapy and who were either ineligible for hematopoietic stem cell transplant or who experienced disease progression after transplant.

Interim results of the study were previously reported at the European Hematology Association Congress in 2017.

At that meeting, Gilles Salles, MD, PhD, from the University of Lyon (France), presented results of an analysis of available efficacy data on 51 patients with at least 3 months of follow-up. In this population, the best overall response rate was 59%. The 3-month overall response rate was 45%, consisting of 37% complete responses and 8% partial responses. Relapse-free survival at 6 months was 79% and all patients who had responses at 3 months continued to have responses at the time of data cutoff.

JULIET now

In the most recent analysis, completed after a median time from infusion to data cutoff of 14 months, the investigators reported on efficacy in 93 patients who received CAR T-cell infusions.

The best overall response rate, the primary endpoint, was 52%, comprising 40% complete responses and 12% partial responses. The response rates were consistent across all prognostic subgroups, including age, sex, previous response status, International Prognostic Index score at enrollment, prior therapy, molecular subtype, and other factors.

Estimated relapse-free survival 12 months after documentation of an initial response was 65%, and was 79% among patients who had complete responses.

The median duration of response had not been reached at the time of data cutoff; the median overall survival had not been reached for patients with a complete remission. Overall survival in this heavily pretreated population as a whole (all patients who received CAR T-cell infusions) was 11.1 months.

Adverse events of special interest included grade 3 or 4 cytokine release syndrome (CRS) in 23% of patients, prolonged cytopenia in 34%, infections in 19%, neurologic events in 11%, febrile neutropenia in 15%, and tumor lysis syndrome in 2%.

There were no deaths attributable to CRS or to cerebral edema, a complication of CAR T-cell therapy that appears to be related to the costimulatory molecule used in various constructs.

“Patients with relapsed or refractory DLBCL who are not eligible for high-dose therapy and hematopoietic cell transplantation or for whom such therapy was not successful have very few treatment options. For these patients, tisagenlecleucel shows promise that will need to be confirmed through larger studies with longer follow-up,” the investigators wrote in the New England Journal of Medicine.

The JULIET Trial is supported by Novartis. Dr. Maziar reported personal fees from Incyte, Kite Therapeutics, and Athersys.

SOURCE: Maziarz RT et al. N Engl J Med. 2018 Dec 1. doi: 10.1056/NEJMoa1804980.
 

SAN DIEGO – Chimeric antigen receptor T-cell therapy with tisagenlecleucel (Kymriah) is associated with a high rate of durable responses in adults with relapsed or refractory diffuse large B-cell lymphoma, an updated analysis of the JULIET trial showed.

Neil Osterweil/MDedge News

After a median follow-up of 19 months, two-thirds of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who had early responses to chimeric antigen receptor (CAR) T-cell therapy with tisagenlecleucel remained in remission with no evidence of minimal residual disease, reported Richard Thomas Maziarz, MD, from the Oregon Health & Science Knight Cancer Institute in Portland, at the annual meeting of the American Society of Hematology.

“Since the previous report, no new deaths have been reported due to any cause other than patient disease progression. No treatment-related mortality was seen throughout the study, and there were three early deaths, all related to lymphoma that progressed,” he said in a briefing prior to presentation of the data in a scientific poster.

The updated study results were published simultaneously online in the New England Journal of Medicine.

JULIET then

In the phase 2, single-arm trial, investigators enrolled adults with DLBCL that had relapsed or was refractory after two or more prior lines of therapy and who were either ineligible for hematopoietic stem cell transplant or who experienced disease progression after transplant.

Interim results of the study were previously reported at the European Hematology Association Congress in 2017.

At that meeting, Gilles Salles, MD, PhD, from the University of Lyon (France), presented results of an analysis of available efficacy data on 51 patients with at least 3 months of follow-up. In this population, the best overall response rate was 59%. The 3-month overall response rate was 45%, consisting of 37% complete responses and 8% partial responses. Relapse-free survival at 6 months was 79% and all patients who had responses at 3 months continued to have responses at the time of data cutoff.

JULIET now

In the most recent analysis, completed after a median time from infusion to data cutoff of 14 months, the investigators reported on efficacy in 93 patients who received CAR T-cell infusions.

The best overall response rate, the primary endpoint, was 52%, comprising 40% complete responses and 12% partial responses. The response rates were consistent across all prognostic subgroups, including age, sex, previous response status, International Prognostic Index score at enrollment, prior therapy, molecular subtype, and other factors.

Estimated relapse-free survival 12 months after documentation of an initial response was 65%, and was 79% among patients who had complete responses.

The median duration of response had not been reached at the time of data cutoff; the median overall survival had not been reached for patients with a complete remission. Overall survival in this heavily pretreated population as a whole (all patients who received CAR T-cell infusions) was 11.1 months.

Adverse events of special interest included grade 3 or 4 cytokine release syndrome (CRS) in 23% of patients, prolonged cytopenia in 34%, infections in 19%, neurologic events in 11%, febrile neutropenia in 15%, and tumor lysis syndrome in 2%.

There were no deaths attributable to CRS or to cerebral edema, a complication of CAR T-cell therapy that appears to be related to the costimulatory molecule used in various constructs.

“Patients with relapsed or refractory DLBCL who are not eligible for high-dose therapy and hematopoietic cell transplantation or for whom such therapy was not successful have very few treatment options. For these patients, tisagenlecleucel shows promise that will need to be confirmed through larger studies with longer follow-up,” the investigators wrote in the New England Journal of Medicine.

The JULIET Trial is supported by Novartis. Dr. Maziar reported personal fees from Incyte, Kite Therapeutics, and Athersys.

SOURCE: Maziarz RT et al. N Engl J Med. 2018 Dec 1. doi: 10.1056/NEJMoa1804980.
 

SAN DIEGO – Chimeric antigen receptor T-cell therapy with tisagenlecleucel (Kymriah) is associated with a high rate of durable responses in adults with relapsed or refractory diffuse large B-cell lymphoma, an updated analysis of the JULIET trial showed.

Neil Osterweil/MDedge News

After a median follow-up of 19 months, two-thirds of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who had early responses to chimeric antigen receptor (CAR) T-cell therapy with tisagenlecleucel remained in remission with no evidence of minimal residual disease, reported Richard Thomas Maziarz, MD, from the Oregon Health & Science Knight Cancer Institute in Portland, at the annual meeting of the American Society of Hematology.

“Since the previous report, no new deaths have been reported due to any cause other than patient disease progression. No treatment-related mortality was seen throughout the study, and there were three early deaths, all related to lymphoma that progressed,” he said in a briefing prior to presentation of the data in a scientific poster.

The updated study results were published simultaneously online in the New England Journal of Medicine.

JULIET then

In the phase 2, single-arm trial, investigators enrolled adults with DLBCL that had relapsed or was refractory after two or more prior lines of therapy and who were either ineligible for hematopoietic stem cell transplant or who experienced disease progression after transplant.

Interim results of the study were previously reported at the European Hematology Association Congress in 2017.

At that meeting, Gilles Salles, MD, PhD, from the University of Lyon (France), presented results of an analysis of available efficacy data on 51 patients with at least 3 months of follow-up. In this population, the best overall response rate was 59%. The 3-month overall response rate was 45%, consisting of 37% complete responses and 8% partial responses. Relapse-free survival at 6 months was 79% and all patients who had responses at 3 months continued to have responses at the time of data cutoff.

JULIET now

In the most recent analysis, completed after a median time from infusion to data cutoff of 14 months, the investigators reported on efficacy in 93 patients who received CAR T-cell infusions.

The best overall response rate, the primary endpoint, was 52%, comprising 40% complete responses and 12% partial responses. The response rates were consistent across all prognostic subgroups, including age, sex, previous response status, International Prognostic Index score at enrollment, prior therapy, molecular subtype, and other factors.

Estimated relapse-free survival 12 months after documentation of an initial response was 65%, and was 79% among patients who had complete responses.

The median duration of response had not been reached at the time of data cutoff; the median overall survival had not been reached for patients with a complete remission. Overall survival in this heavily pretreated population as a whole (all patients who received CAR T-cell infusions) was 11.1 months.

Adverse events of special interest included grade 3 or 4 cytokine release syndrome (CRS) in 23% of patients, prolonged cytopenia in 34%, infections in 19%, neurologic events in 11%, febrile neutropenia in 15%, and tumor lysis syndrome in 2%.

There were no deaths attributable to CRS or to cerebral edema, a complication of CAR T-cell therapy that appears to be related to the costimulatory molecule used in various constructs.

“Patients with relapsed or refractory DLBCL who are not eligible for high-dose therapy and hematopoietic cell transplantation or for whom such therapy was not successful have very few treatment options. For these patients, tisagenlecleucel shows promise that will need to be confirmed through larger studies with longer follow-up,” the investigators wrote in the New England Journal of Medicine.

The JULIET Trial is supported by Novartis. Dr. Maziar reported personal fees from Incyte, Kite Therapeutics, and Athersys.

SOURCE: Maziarz RT et al. N Engl J Med. 2018 Dec 1. doi: 10.1056/NEJMoa1804980.
 

SAN DIEGO – A single infusion of tisagenlecleucel (Kymriah) continues to demonstrate high efficacy a year and a half after pediatric and young adult patients with relapsed or refractory acute lymphoblastic leukemia (ALL) were enrolled in the pivotal ELIANA trial, Stephan A. Grupp, MD, PhD, reported at a press conference at the annual meeting of the American Society of Hematology.

Neil Osterweil/MDedge News

Of patients in complete remission after receiving the chimeric antigen receptor (CAR) T-cell therapy, 66% were still in remission at 18 months of follow-up and median survival has yet to be reached.

“We think the efficacy is sustained and excellent,” said Dr. Grupp, of the University of Pennsylvania, Philadelphia. “These are durable complete responses even without further therapy. We haven’t reached median duration of response or overall survival, and we can manage toxicity, so I think this is clearly an opportunity for us to treat our patients both in America and across the world.”

The results of ELIANA were the basis for the approval of tisagenlecleucel (Kymriah) for relapsed/refractory B-cell ALL in the United States, and for subsequent approvals by health authorities in the European Union, Switzerland, and Canada.

The international, single-arm, open-label, phase 2 ELIANA trial 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-cell therapy.

The rate of overall remission, defined as the rate of complete remission or complete remission with incomplete blood count recovery, was 82% (65 patients). Among those patients, 66% were still in remission at 18 months, while overall survival was “excellent” at 70%, Dr. Grupp said, and the median overall survival was not reached.

Adverse events prevalence remained relatively unchanged since the previous analyses, according to Dr. Grupp, who added that appropriately trained personnel were able to effectively manage those adverse events across study sites. Cytokine release syndrome (CRS) occurred in 77% of patients. All cases were reversible; 39% received tocilizumab for treatment of CRS with or without other anticytokine therapies; 48% required ICU-level care for CRS, with a median ICU stay of 7 days.

The other most common grade 3/4 nonhematologic adverse events were neutropenia with a body temperature exceeding 38.3° C (62% within 8 weeks of infusion), hypoxia (20%), and hypotension (20%). Grade 3 neurologic effects occurred in 13% of patients, and none had cerebral edema. Based on laboratory results, 43% had grade 3/4 thrombocytopenia and 54% had neutropenia not resolved by day 28; most of these events resolved to grade 2 or less by 3 months.

There were 25 postinfusion deaths, with 2 occurring within 30 days (1 because of disease progression, 1 because of cerebral hemorrhage). Of the 23 deaths after 30 days (range, 53-859 days), 18 were caused by disease progression. The other deaths were caused by encephalitis, systemic mycosis, vasoocclusive hepatobiliary disorder related to allogeneic SCT, bacterial lung infection, and an unknown reason after study withdrawal.

Follow-up is ongoing in the ELIANA study, which is supported by Novartis, the maker of Kymriah.

Dr. Grupp reported research funding from Novartis, consultancy with Novartis, Jazz Pharmaceuticals, and Adaptimmune Therapeutics, and patents or royalties with the University of Pennsylvania.

SOURCE: Grupp SA et al. ASH 2018, Abstract 895.

SAN DIEGO – A single infusion of tisagenlecleucel (Kymriah) continues to demonstrate high efficacy a year and a half after pediatric and young adult patients with relapsed or refractory acute lymphoblastic leukemia (ALL) were enrolled in the pivotal ELIANA trial, Stephan A. Grupp, MD, PhD, reported at a press conference at the annual meeting of the American Society of Hematology.

Neil Osterweil/MDedge News

Of patients in complete remission after receiving the chimeric antigen receptor (CAR) T-cell therapy, 66% were still in remission at 18 months of follow-up and median survival has yet to be reached.

“We think the efficacy is sustained and excellent,” said Dr. Grupp, of the University of Pennsylvania, Philadelphia. “These are durable complete responses even without further therapy. We haven’t reached median duration of response or overall survival, and we can manage toxicity, so I think this is clearly an opportunity for us to treat our patients both in America and across the world.”

The results of ELIANA were the basis for the approval of tisagenlecleucel (Kymriah) for relapsed/refractory B-cell ALL in the United States, and for subsequent approvals by health authorities in the European Union, Switzerland, and Canada.

The international, single-arm, open-label, phase 2 ELIANA trial 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-cell therapy.

The rate of overall remission, defined as the rate of complete remission or complete remission with incomplete blood count recovery, was 82% (65 patients). Among those patients, 66% were still in remission at 18 months, while overall survival was “excellent” at 70%, Dr. Grupp said, and the median overall survival was not reached.

Adverse events prevalence remained relatively unchanged since the previous analyses, according to Dr. Grupp, who added that appropriately trained personnel were able to effectively manage those adverse events across study sites. Cytokine release syndrome (CRS) occurred in 77% of patients. All cases were reversible; 39% received tocilizumab for treatment of CRS with or without other anticytokine therapies; 48% required ICU-level care for CRS, with a median ICU stay of 7 days.

The other most common grade 3/4 nonhematologic adverse events were neutropenia with a body temperature exceeding 38.3° C (62% within 8 weeks of infusion), hypoxia (20%), and hypotension (20%). Grade 3 neurologic effects occurred in 13% of patients, and none had cerebral edema. Based on laboratory results, 43% had grade 3/4 thrombocytopenia and 54% had neutropenia not resolved by day 28; most of these events resolved to grade 2 or less by 3 months.

There were 25 postinfusion deaths, with 2 occurring within 30 days (1 because of disease progression, 1 because of cerebral hemorrhage). Of the 23 deaths after 30 days (range, 53-859 days), 18 were caused by disease progression. The other deaths were caused by encephalitis, systemic mycosis, vasoocclusive hepatobiliary disorder related to allogeneic SCT, bacterial lung infection, and an unknown reason after study withdrawal.

Follow-up is ongoing in the ELIANA study, which is supported by Novartis, the maker of Kymriah.

Dr. Grupp reported research funding from Novartis, consultancy with Novartis, Jazz Pharmaceuticals, and Adaptimmune Therapeutics, and patents or royalties with the University of Pennsylvania.

SOURCE: Grupp SA et al. ASH 2018, Abstract 895.

SAN DIEGO – A single infusion of tisagenlecleucel (Kymriah) continues to demonstrate high efficacy a year and a half after pediatric and young adult patients with relapsed or refractory acute lymphoblastic leukemia (ALL) were enrolled in the pivotal ELIANA trial, Stephan A. Grupp, MD, PhD, reported at a press conference at the annual meeting of the American Society of Hematology.

Neil Osterweil/MDedge News

Of patients in complete remission after receiving the chimeric antigen receptor (CAR) T-cell therapy, 66% were still in remission at 18 months of follow-up and median survival has yet to be reached.

“We think the efficacy is sustained and excellent,” said Dr. Grupp, of the University of Pennsylvania, Philadelphia. “These are durable complete responses even without further therapy. We haven’t reached median duration of response or overall survival, and we can manage toxicity, so I think this is clearly an opportunity for us to treat our patients both in America and across the world.”

The results of ELIANA were the basis for the approval of tisagenlecleucel (Kymriah) for relapsed/refractory B-cell ALL in the United States, and for subsequent approvals by health authorities in the European Union, Switzerland, and Canada.

The international, single-arm, open-label, phase 2 ELIANA trial 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-cell therapy.

The rate of overall remission, defined as the rate of complete remission or complete remission with incomplete blood count recovery, was 82% (65 patients). Among those patients, 66% were still in remission at 18 months, while overall survival was “excellent” at 70%, Dr. Grupp said, and the median overall survival was not reached.

Adverse events prevalence remained relatively unchanged since the previous analyses, according to Dr. Grupp, who added that appropriately trained personnel were able to effectively manage those adverse events across study sites. Cytokine release syndrome (CRS) occurred in 77% of patients. All cases were reversible; 39% received tocilizumab for treatment of CRS with or without other anticytokine therapies; 48% required ICU-level care for CRS, with a median ICU stay of 7 days.

The other most common grade 3/4 nonhematologic adverse events were neutropenia with a body temperature exceeding 38.3° C (62% within 8 weeks of infusion), hypoxia (20%), and hypotension (20%). Grade 3 neurologic effects occurred in 13% of patients, and none had cerebral edema. Based on laboratory results, 43% had grade 3/4 thrombocytopenia and 54% had neutropenia not resolved by day 28; most of these events resolved to grade 2 or less by 3 months.

There were 25 postinfusion deaths, with 2 occurring within 30 days (1 because of disease progression, 1 because of cerebral hemorrhage). Of the 23 deaths after 30 days (range, 53-859 days), 18 were caused by disease progression. The other deaths were caused by encephalitis, systemic mycosis, vasoocclusive hepatobiliary disorder related to allogeneic SCT, bacterial lung infection, and an unknown reason after study withdrawal.

Follow-up is ongoing in the ELIANA study, which is supported by Novartis, the maker of Kymriah.

Dr. Grupp reported research funding from Novartis, consultancy with Novartis, Jazz Pharmaceuticals, and Adaptimmune Therapeutics, and patents or royalties with the University of Pennsylvania.

SOURCE: Grupp SA et al. ASH 2018, Abstract 895.

SAN DIEGO – Inpatient deaths from opioid overdose in the U.S. population has risen dramatically in recent years, but this is essentially a “never event” among patients with sickle cell disease (SCD).

These findings come from an analysis of hospital discharge data in the National Inpatient Sample from 1998 to 2013. Oladimeji Akinola Akinboro, MBBS, who led the study, said the findings suggest that the current patterns of opioid use in SCD patients are safe and that opioids should not be withheld when they are appropriate.

From 1998 to 2013, the rate of inpatient deaths from opioid overdose in the United States rose 350% overall and approximately 8% annually. In contrast, deaths among SCD patients were flat, with a rate at or near zero throughout the same time period.

Over the 16-year period, there were just nine deaths reported among SCD patients because of opioids in the inpatient setting, Dr. Akinboro of Boston University Medical Center reported at the annual meeting of the American Society of Hematology.

While the reasons behind the difference were not explored in the study, Dr. Akinboro suggested that the sickle cell community has greater experience with opioids and that patients and physicians typically have long-standing clinical relationships that make mitigation of opioid misuse easier to manage.

Opioid-related hospitalizations, however, were comparable among the general U.S. population and SCD patients. And for both groups the rates remained relatively steady throughout the study period, with the exception of a drop among SCD patients in 2002, he noted.

The study also revealed age-related trends in hospitalizations overall. Hospitalizations among sickle cell patients were stable from 1998 to 2013. However, when the researchers broke the data down by age they found that adults aged 18-44 years had an increase in hospitalizations, with the steepest rise in patients aged 65 years and older.

In total, there were more than 1.7 million hospitalizations among SCD patients in the United States from 1998 to 2013. The rate declined by 9.9% each year from 1998 to 2002, then remained flat at around 27 per 100,000 persons from 2002 to 2013.

However, for adults aged 18-44 years, hospitalizations increased from 43 per 100,000 persons in 2002 to 71 per 100,000 persons in 2013 – an annual increase of 3.8%. Patients aged 65 years and older saw their rate of hospitalization increase from 2.7 to 5.4 per 100,000 persons from 1998 to 2013 – a 6.5% increase for each year.

The study did not explore the causes behind the age-related trends but Dr. Akinboro suggested it may be because of fragmentation of adult SCD care and age- and pain-related medical comorbidities.

The researchers reported having no relevant financial disclosures.

mschneider@mdedge.com

SOURCE: Akinboro OA et al. ASH 2018, Abstract 315.

SAN DIEGO – Inpatient deaths from opioid overdose in the U.S. population has risen dramatically in recent years, but this is essentially a “never event” among patients with sickle cell disease (SCD).

These findings come from an analysis of hospital discharge data in the National Inpatient Sample from 1998 to 2013. Oladimeji Akinola Akinboro, MBBS, who led the study, said the findings suggest that the current patterns of opioid use in SCD patients are safe and that opioids should not be withheld when they are appropriate.

From 1998 to 2013, the rate of inpatient deaths from opioid overdose in the United States rose 350% overall and approximately 8% annually. In contrast, deaths among SCD patients were flat, with a rate at or near zero throughout the same time period.

Over the 16-year period, there were just nine deaths reported among SCD patients because of opioids in the inpatient setting, Dr. Akinboro of Boston University Medical Center reported at the annual meeting of the American Society of Hematology.

While the reasons behind the difference were not explored in the study, Dr. Akinboro suggested that the sickle cell community has greater experience with opioids and that patients and physicians typically have long-standing clinical relationships that make mitigation of opioid misuse easier to manage.

Opioid-related hospitalizations, however, were comparable among the general U.S. population and SCD patients. And for both groups the rates remained relatively steady throughout the study period, with the exception of a drop among SCD patients in 2002, he noted.

The study also revealed age-related trends in hospitalizations overall. Hospitalizations among sickle cell patients were stable from 1998 to 2013. However, when the researchers broke the data down by age they found that adults aged 18-44 years had an increase in hospitalizations, with the steepest rise in patients aged 65 years and older.

In total, there were more than 1.7 million hospitalizations among SCD patients in the United States from 1998 to 2013. The rate declined by 9.9% each year from 1998 to 2002, then remained flat at around 27 per 100,000 persons from 2002 to 2013.

However, for adults aged 18-44 years, hospitalizations increased from 43 per 100,000 persons in 2002 to 71 per 100,000 persons in 2013 – an annual increase of 3.8%. Patients aged 65 years and older saw their rate of hospitalization increase from 2.7 to 5.4 per 100,000 persons from 1998 to 2013 – a 6.5% increase for each year.

The study did not explore the causes behind the age-related trends but Dr. Akinboro suggested it may be because of fragmentation of adult SCD care and age- and pain-related medical comorbidities.

The researchers reported having no relevant financial disclosures.

mschneider@mdedge.com

SOURCE: Akinboro OA et al. ASH 2018, Abstract 315.

SAN DIEGO – Inpatient deaths from opioid overdose in the U.S. population has risen dramatically in recent years, but this is essentially a “never event” among patients with sickle cell disease (SCD).

These findings come from an analysis of hospital discharge data in the National Inpatient Sample from 1998 to 2013. Oladimeji Akinola Akinboro, MBBS, who led the study, said the findings suggest that the current patterns of opioid use in SCD patients are safe and that opioids should not be withheld when they are appropriate.

From 1998 to 2013, the rate of inpatient deaths from opioid overdose in the United States rose 350% overall and approximately 8% annually. In contrast, deaths among SCD patients were flat, with a rate at or near zero throughout the same time period.

Over the 16-year period, there were just nine deaths reported among SCD patients because of opioids in the inpatient setting, Dr. Akinboro of Boston University Medical Center reported at the annual meeting of the American Society of Hematology.

While the reasons behind the difference were not explored in the study, Dr. Akinboro suggested that the sickle cell community has greater experience with opioids and that patients and physicians typically have long-standing clinical relationships that make mitigation of opioid misuse easier to manage.

Opioid-related hospitalizations, however, were comparable among the general U.S. population and SCD patients. And for both groups the rates remained relatively steady throughout the study period, with the exception of a drop among SCD patients in 2002, he noted.

The study also revealed age-related trends in hospitalizations overall. Hospitalizations among sickle cell patients were stable from 1998 to 2013. However, when the researchers broke the data down by age they found that adults aged 18-44 years had an increase in hospitalizations, with the steepest rise in patients aged 65 years and older.

In total, there were more than 1.7 million hospitalizations among SCD patients in the United States from 1998 to 2013. The rate declined by 9.9% each year from 1998 to 2002, then remained flat at around 27 per 100,000 persons from 2002 to 2013.

However, for adults aged 18-44 years, hospitalizations increased from 43 per 100,000 persons in 2002 to 71 per 100,000 persons in 2013 – an annual increase of 3.8%. Patients aged 65 years and older saw their rate of hospitalization increase from 2.7 to 5.4 per 100,000 persons from 1998 to 2013 – a 6.5% increase for each year.

The study did not explore the causes behind the age-related trends but Dr. Akinboro suggested it may be because of fragmentation of adult SCD care and age- and pain-related medical comorbidities.

The researchers reported having no relevant financial disclosures.

mschneider@mdedge.com

SOURCE: Akinboro OA et al. ASH 2018, Abstract 315.

SAN DIEGO – A novel erythroid maturation agent significantly reduced transfusion burden versus placebo in patients with anemia caused by myelodysplastic syndromes (MDS) and ringed sideroblasts, results of a randomized, phase 3 trial demonstrate.

Luspatercept was “very well tolerated” and responses were durable, with approximately 40% of patients remaining transfusion free after 1 year of therapy, said Alan F. List, MD, of Moffitt Cancer Center, Tampa.

“Luspatercept is a potential new therapy that we think could be very effective in patients with lower-risk MDS with ringed sideroblasts who are red blood cell transfusion–dependent,” said Dr. List, senior author of the MEDALIST trial, said in a press conference at the annual meeting of the American Society of Hematology.

The first-in-class erythroid maturation agent is being developed as a treatment for anemia related to MDS and beta-thalassemia, Dr. List said.

In a separate randomized, placebo-controlled, phase 3 study presented at ASH 2018, Maria Domenica Cappellini, MD, of the University of Milan, reported that, in beta-thalassemia patients who were transfusion dependent, luspatercept treatment resulted in a statistically significant reductions in transfusion burden versus placebo, and was generally well tolerated.

Luspatercept is a soluble receptor chimera that binds to an array of ligands in the transforming growth factor–beta superfamily, which is known to be important in suppressing erythropoiesis in patients with MDS, Dr. List said.

The MDS study included patients with very low–, low-, or intermediate-risk disease and ringed sideroblasts who were RBC transfusion–dependent and were refractory to, unresponsive to, or ineligible for first-line treatment with an erythropoiesis-stimulating agent (ESA).

A total of 153 patients were randomly allocated to luspatercept 1.0 mg/kg, administered subcutaneously every 21 days for at least 24 weeks, while 76 were randomized to placebo every 21 days. The primary end point was the proportion of patients achieving RBC transfusion independence for at least 8 weeks during the first 24 weeks of treatment.

A total of 37.9% of luspatercept-treated patients achieved that primary endpoint, compared with 13.2% of placebo-treated patient (P less than .0001), Dr. List reported. The luspatercept-treated patients also had a 52.9% rate of erythroid response, compared with 11.8% in the placebo group (P less than .0001).

There were no differences in treatment-emergent adverse events, severe adverse events, or frequency of progression of acute myeloid leukemia. “This was a very clean drug and a very safe drug,” he said.

The decision to study luspatercept in patients with ringed sideroblasts was based on results of a large, phase 2 European study showing a higher response rate in that subset of MDS patients, according to Dr. List.

That study also included a small number of patients who had not previously received an ESA. Currently underway is a phase 3 trial looking at luspatercept in ESA-naive, lower-risk MDS patients with anemia who require RBC transfusions.

Luspatercept would be a useful therapy to have in clinic for patients with ring sideroblasts, who represent about 25% of patients overall, according to MDS expert David Steensma, MD, of Dana-Farber Cancer Institute and Harvard Medical School, Boston.

“It’s been 12 years since we had an FDA [Food and Drug Administration]-approved drug in MDS, and there have been seven in acute myeloid leukemia in the last year and a half, so it’s our turn, I think,” said Dr. Steensma, who moderated the press conference.

Dr. List reported research funding from Celgene.

SOURCE: List AF et al. ASH 2018, Abstract 1.

SAN DIEGO – A novel erythroid maturation agent significantly reduced transfusion burden versus placebo in patients with anemia caused by myelodysplastic syndromes (MDS) and ringed sideroblasts, results of a randomized, phase 3 trial demonstrate.

Luspatercept was “very well tolerated” and responses were durable, with approximately 40% of patients remaining transfusion free after 1 year of therapy, said Alan F. List, MD, of Moffitt Cancer Center, Tampa.

“Luspatercept is a potential new therapy that we think could be very effective in patients with lower-risk MDS with ringed sideroblasts who are red blood cell transfusion–dependent,” said Dr. List, senior author of the MEDALIST trial, said in a press conference at the annual meeting of the American Society of Hematology.

The first-in-class erythroid maturation agent is being developed as a treatment for anemia related to MDS and beta-thalassemia, Dr. List said.

In a separate randomized, placebo-controlled, phase 3 study presented at ASH 2018, Maria Domenica Cappellini, MD, of the University of Milan, reported that, in beta-thalassemia patients who were transfusion dependent, luspatercept treatment resulted in a statistically significant reductions in transfusion burden versus placebo, and was generally well tolerated.

Luspatercept is a soluble receptor chimera that binds to an array of ligands in the transforming growth factor–beta superfamily, which is known to be important in suppressing erythropoiesis in patients with MDS, Dr. List said.

The MDS study included patients with very low–, low-, or intermediate-risk disease and ringed sideroblasts who were RBC transfusion–dependent and were refractory to, unresponsive to, or ineligible for first-line treatment with an erythropoiesis-stimulating agent (ESA).

A total of 153 patients were randomly allocated to luspatercept 1.0 mg/kg, administered subcutaneously every 21 days for at least 24 weeks, while 76 were randomized to placebo every 21 days. The primary end point was the proportion of patients achieving RBC transfusion independence for at least 8 weeks during the first 24 weeks of treatment.

A total of 37.9% of luspatercept-treated patients achieved that primary endpoint, compared with 13.2% of placebo-treated patient (P less than .0001), Dr. List reported. The luspatercept-treated patients also had a 52.9% rate of erythroid response, compared with 11.8% in the placebo group (P less than .0001).

There were no differences in treatment-emergent adverse events, severe adverse events, or frequency of progression of acute myeloid leukemia. “This was a very clean drug and a very safe drug,” he said.

The decision to study luspatercept in patients with ringed sideroblasts was based on results of a large, phase 2 European study showing a higher response rate in that subset of MDS patients, according to Dr. List.

That study also included a small number of patients who had not previously received an ESA. Currently underway is a phase 3 trial looking at luspatercept in ESA-naive, lower-risk MDS patients with anemia who require RBC transfusions.

Luspatercept would be a useful therapy to have in clinic for patients with ring sideroblasts, who represent about 25% of patients overall, according to MDS expert David Steensma, MD, of Dana-Farber Cancer Institute and Harvard Medical School, Boston.

“It’s been 12 years since we had an FDA [Food and Drug Administration]-approved drug in MDS, and there have been seven in acute myeloid leukemia in the last year and a half, so it’s our turn, I think,” said Dr. Steensma, who moderated the press conference.

Dr. List reported research funding from Celgene.

SOURCE: List AF et al. ASH 2018, Abstract 1.

SAN DIEGO – A novel erythroid maturation agent significantly reduced transfusion burden versus placebo in patients with anemia caused by myelodysplastic syndromes (MDS) and ringed sideroblasts, results of a randomized, phase 3 trial demonstrate.

Luspatercept was “very well tolerated” and responses were durable, with approximately 40% of patients remaining transfusion free after 1 year of therapy, said Alan F. List, MD, of Moffitt Cancer Center, Tampa.

“Luspatercept is a potential new therapy that we think could be very effective in patients with lower-risk MDS with ringed sideroblasts who are red blood cell transfusion–dependent,” said Dr. List, senior author of the MEDALIST trial, said in a press conference at the annual meeting of the American Society of Hematology.

The first-in-class erythroid maturation agent is being developed as a treatment for anemia related to MDS and beta-thalassemia, Dr. List said.

In a separate randomized, placebo-controlled, phase 3 study presented at ASH 2018, Maria Domenica Cappellini, MD, of the University of Milan, reported that, in beta-thalassemia patients who were transfusion dependent, luspatercept treatment resulted in a statistically significant reductions in transfusion burden versus placebo, and was generally well tolerated.

Luspatercept is a soluble receptor chimera that binds to an array of ligands in the transforming growth factor–beta superfamily, which is known to be important in suppressing erythropoiesis in patients with MDS, Dr. List said.

The MDS study included patients with very low–, low-, or intermediate-risk disease and ringed sideroblasts who were RBC transfusion–dependent and were refractory to, unresponsive to, or ineligible for first-line treatment with an erythropoiesis-stimulating agent (ESA).

A total of 153 patients were randomly allocated to luspatercept 1.0 mg/kg, administered subcutaneously every 21 days for at least 24 weeks, while 76 were randomized to placebo every 21 days. The primary end point was the proportion of patients achieving RBC transfusion independence for at least 8 weeks during the first 24 weeks of treatment.

A total of 37.9% of luspatercept-treated patients achieved that primary endpoint, compared with 13.2% of placebo-treated patient (P less than .0001), Dr. List reported. The luspatercept-treated patients also had a 52.9% rate of erythroid response, compared with 11.8% in the placebo group (P less than .0001).

There were no differences in treatment-emergent adverse events, severe adverse events, or frequency of progression of acute myeloid leukemia. “This was a very clean drug and a very safe drug,” he said.

The decision to study luspatercept in patients with ringed sideroblasts was based on results of a large, phase 2 European study showing a higher response rate in that subset of MDS patients, according to Dr. List.

That study also included a small number of patients who had not previously received an ESA. Currently underway is a phase 3 trial looking at luspatercept in ESA-naive, lower-risk MDS patients with anemia who require RBC transfusions.

Luspatercept would be a useful therapy to have in clinic for patients with ring sideroblasts, who represent about 25% of patients overall, according to MDS expert David Steensma, MD, of Dana-Farber Cancer Institute and Harvard Medical School, Boston.

“It’s been 12 years since we had an FDA [Food and Drug Administration]-approved drug in MDS, and there have been seven in acute myeloid leukemia in the last year and a half, so it’s our turn, I think,” said Dr. Steensma, who moderated the press conference.

Dr. List reported research funding from Celgene.

SOURCE: List AF et al. ASH 2018, Abstract 1.

SAN DIEGO – A shortened regimen of four cycles of rituximab plus CHOP chemotherapy was noninferior in efficacy to the standard six cycles of R-CHOP in patients aged under age 60 years with favorable-risk diffuse large B-cell lymphoma (DLBCL), and the truncated regimen was associated with about a one-third reduction in nonhematologic adverse events, investigators in the FLYER trial reported.

Neil Osterweil/MDedge News

Among 588 evaluable patients aged younger than 60 years with favorable-prognosis diffuse DLBCL, there were no significant differences in either progression-free survival (PFS), event-free survival, or overall survival (OS) between patients who were randomly assigned to therapy with four cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), compared with patients assigned to six cycles, reported Viola Poeschel, MD, of Saarland University in Homburg, Germany.

“Six cycles of R-CHOP led to a higher toxicity with respect to leukocytopenia and anemia, both of any grades and also of grades 3 to 4, compared to four cycles of R-CHOP,” she said in a briefing at the annual meeting of the American Society of Hematology.

For younger patients with favorable-prognosis DLBCL – defined as an age-adjusted International Prognostic Index score of 0 and low tumor burden (less than 7.5 cm) – four cycles of R-CHOP can be a new standard of care, Dr. Poeschel said.

The investigators were prompted to look at the question of a shorter R-CHOP regimen by the results of the MInT trial, in which a subpopulation of favorable-prognosis DLBCL had a 3-year PFS rate of 89% (Lancet Oncol. 2006 May;7[5]379-91). The FLYER trial was designed as a noninferiority study to see whether in a similar group of patients reducing the number of R-CHOP cycles could maintain efficacy while reducing toxicity.

At a median follow-up of 66 months, the PFS rate, the primary endpoint, was 94% in the R-CHOP 6 group, compared with 96% for R-CHOP 4.

“As the lower limit of the 95% confidence interval of our experimental arm was 94%, it is shown that it is definitely noninferior to the standard arm, six cycles of R-CHOP,” Dr. Poeschel said.

Similarly, the rate of 3-year OS was 98% in the six-cycle group, compared with 99% in the four-cycle group, and the survival curves were virtually superimposable out to more than 10 years of follow-up.

R-CHOP 6 was associated with more frequent hematologic adverse events, compared with R-CHOP 4, with leukopenia of any grade occurring in 237 versus 171 patients, respectively, and grade 3 or 4 events occurring in 110 versus 80 patients, respectively.

Any grade anemia occurred in 172 patients assigned to six cycles versus 107 assigned to four cycles. Rates of grade 3-4 anemia and thrombocytopenia of any grade or of grade 3-4 were similar between the groups.

Nonhematologic adverse events of any grade or of grade 3 or 4 that were more frequent with R-CHOP 6 versus R-CHOP 4 included all events considered together, paresthesias, nausea, infection, vomiting, and mucositis.

As noted before, the total number of nonhematologic adverse events was reduced by about one-third.

Neil Osterweil/MDedge News

“We are certainly always looking for ways to make treatments easier for our patients to reduce adverse effects, and certainly for this subgroup of patients it appears that we can make their treatment shorter and have less burden but equivalent efficacy,” commented David Steensma, MD, from the Dana-Farber Cancer Institute/Harvard Cancer Center in Boston, who moderated the briefing.

Dr. Steensma and Dr. Poeschel both cautioned that the results of the study pertain only to those patients with DLBCL who are younger and have favorable-prognosis disease.

“We can’t extend it to other subtypes of large cell lymphoma, but that’s always a laudable goal, so I think this will immediately influence clinical practice,” Dr. Steensma said.

The study was sponsored by the German High-Grade Non-Hodgkin’s Lymphoma Study Group. Dr. Poeschel reporteed travel grants from Roche and Amgen. Dr. Steensma reported no disclosures relevant to the study.

SOURCE: Poeschel V et al. ASH 2018, Abstract 781.

SAN DIEGO – A shortened regimen of four cycles of rituximab plus CHOP chemotherapy was noninferior in efficacy to the standard six cycles of R-CHOP in patients aged under age 60 years with favorable-risk diffuse large B-cell lymphoma (DLBCL), and the truncated regimen was associated with about a one-third reduction in nonhematologic adverse events, investigators in the FLYER trial reported.

Neil Osterweil/MDedge News

Among 588 evaluable patients aged younger than 60 years with favorable-prognosis diffuse DLBCL, there were no significant differences in either progression-free survival (PFS), event-free survival, or overall survival (OS) between patients who were randomly assigned to therapy with four cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), compared with patients assigned to six cycles, reported Viola Poeschel, MD, of Saarland University in Homburg, Germany.

“Six cycles of R-CHOP led to a higher toxicity with respect to leukocytopenia and anemia, both of any grades and also of grades 3 to 4, compared to four cycles of R-CHOP,” she said in a briefing at the annual meeting of the American Society of Hematology.

For younger patients with favorable-prognosis DLBCL – defined as an age-adjusted International Prognostic Index score of 0 and low tumor burden (less than 7.5 cm) – four cycles of R-CHOP can be a new standard of care, Dr. Poeschel said.

The investigators were prompted to look at the question of a shorter R-CHOP regimen by the results of the MInT trial, in which a subpopulation of favorable-prognosis DLBCL had a 3-year PFS rate of 89% (Lancet Oncol. 2006 May;7[5]379-91). The FLYER trial was designed as a noninferiority study to see whether in a similar group of patients reducing the number of R-CHOP cycles could maintain efficacy while reducing toxicity.

At a median follow-up of 66 months, the PFS rate, the primary endpoint, was 94% in the R-CHOP 6 group, compared with 96% for R-CHOP 4.

“As the lower limit of the 95% confidence interval of our experimental arm was 94%, it is shown that it is definitely noninferior to the standard arm, six cycles of R-CHOP,” Dr. Poeschel said.

Similarly, the rate of 3-year OS was 98% in the six-cycle group, compared with 99% in the four-cycle group, and the survival curves were virtually superimposable out to more than 10 years of follow-up.

R-CHOP 6 was associated with more frequent hematologic adverse events, compared with R-CHOP 4, with leukopenia of any grade occurring in 237 versus 171 patients, respectively, and grade 3 or 4 events occurring in 110 versus 80 patients, respectively.

Any grade anemia occurred in 172 patients assigned to six cycles versus 107 assigned to four cycles. Rates of grade 3-4 anemia and thrombocytopenia of any grade or of grade 3-4 were similar between the groups.

Nonhematologic adverse events of any grade or of grade 3 or 4 that were more frequent with R-CHOP 6 versus R-CHOP 4 included all events considered together, paresthesias, nausea, infection, vomiting, and mucositis.

As noted before, the total number of nonhematologic adverse events was reduced by about one-third.

Neil Osterweil/MDedge News

“We are certainly always looking for ways to make treatments easier for our patients to reduce adverse effects, and certainly for this subgroup of patients it appears that we can make their treatment shorter and have less burden but equivalent efficacy,” commented David Steensma, MD, from the Dana-Farber Cancer Institute/Harvard Cancer Center in Boston, who moderated the briefing.

Dr. Steensma and Dr. Poeschel both cautioned that the results of the study pertain only to those patients with DLBCL who are younger and have favorable-prognosis disease.

“We can’t extend it to other subtypes of large cell lymphoma, but that’s always a laudable goal, so I think this will immediately influence clinical practice,” Dr. Steensma said.

The study was sponsored by the German High-Grade Non-Hodgkin’s Lymphoma Study Group. Dr. Poeschel reporteed travel grants from Roche and Amgen. Dr. Steensma reported no disclosures relevant to the study.

SOURCE: Poeschel V et al. ASH 2018, Abstract 781.

SAN DIEGO – A shortened regimen of four cycles of rituximab plus CHOP chemotherapy was noninferior in efficacy to the standard six cycles of R-CHOP in patients aged under age 60 years with favorable-risk diffuse large B-cell lymphoma (DLBCL), and the truncated regimen was associated with about a one-third reduction in nonhematologic adverse events, investigators in the FLYER trial reported.

Neil Osterweil/MDedge News

Among 588 evaluable patients aged younger than 60 years with favorable-prognosis diffuse DLBCL, there were no significant differences in either progression-free survival (PFS), event-free survival, or overall survival (OS) between patients who were randomly assigned to therapy with four cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), compared with patients assigned to six cycles, reported Viola Poeschel, MD, of Saarland University in Homburg, Germany.

“Six cycles of R-CHOP led to a higher toxicity with respect to leukocytopenia and anemia, both of any grades and also of grades 3 to 4, compared to four cycles of R-CHOP,” she said in a briefing at the annual meeting of the American Society of Hematology.

For younger patients with favorable-prognosis DLBCL – defined as an age-adjusted International Prognostic Index score of 0 and low tumor burden (less than 7.5 cm) – four cycles of R-CHOP can be a new standard of care, Dr. Poeschel said.

The investigators were prompted to look at the question of a shorter R-CHOP regimen by the results of the MInT trial, in which a subpopulation of favorable-prognosis DLBCL had a 3-year PFS rate of 89% (Lancet Oncol. 2006 May;7[5]379-91). The FLYER trial was designed as a noninferiority study to see whether in a similar group of patients reducing the number of R-CHOP cycles could maintain efficacy while reducing toxicity.

At a median follow-up of 66 months, the PFS rate, the primary endpoint, was 94% in the R-CHOP 6 group, compared with 96% for R-CHOP 4.

“As the lower limit of the 95% confidence interval of our experimental arm was 94%, it is shown that it is definitely noninferior to the standard arm, six cycles of R-CHOP,” Dr. Poeschel said.

Similarly, the rate of 3-year OS was 98% in the six-cycle group, compared with 99% in the four-cycle group, and the survival curves were virtually superimposable out to more than 10 years of follow-up.

R-CHOP 6 was associated with more frequent hematologic adverse events, compared with R-CHOP 4, with leukopenia of any grade occurring in 237 versus 171 patients, respectively, and grade 3 or 4 events occurring in 110 versus 80 patients, respectively.

Any grade anemia occurred in 172 patients assigned to six cycles versus 107 assigned to four cycles. Rates of grade 3-4 anemia and thrombocytopenia of any grade or of grade 3-4 were similar between the groups.

Nonhematologic adverse events of any grade or of grade 3 or 4 that were more frequent with R-CHOP 6 versus R-CHOP 4 included all events considered together, paresthesias, nausea, infection, vomiting, and mucositis.

As noted before, the total number of nonhematologic adverse events was reduced by about one-third.

Neil Osterweil/MDedge News

“We are certainly always looking for ways to make treatments easier for our patients to reduce adverse effects, and certainly for this subgroup of patients it appears that we can make their treatment shorter and have less burden but equivalent efficacy,” commented David Steensma, MD, from the Dana-Farber Cancer Institute/Harvard Cancer Center in Boston, who moderated the briefing.

Dr. Steensma and Dr. Poeschel both cautioned that the results of the study pertain only to those patients with DLBCL who are younger and have favorable-prognosis disease.

“We can’t extend it to other subtypes of large cell lymphoma, but that’s always a laudable goal, so I think this will immediately influence clinical practice,” Dr. Steensma said.

The study was sponsored by the German High-Grade Non-Hodgkin’s Lymphoma Study Group. Dr. Poeschel reporteed travel grants from Roche and Amgen. Dr. Steensma reported no disclosures relevant to the study.

SOURCE: Poeschel V et al. ASH 2018, Abstract 781.

SAN DIEGO – A hematopoietic cell transplant following chimeric antigen receptor (CAR) T-cell therapy for B-cell acute lymphocytic leukemia (B-ALL) may reduce late relapse risk in certain patients, a retrospective analysis suggests.

Corinne Summers, MD, of Seattle Children’s Hospital, and her colleagues evaluated the potential benefits of allogeneic hematopoietic cell transplant (HCT) in 50 pediatric and young adult B-ALL patients who had sustained leukemic remission after receiving SCRI-CAR19v1, a CD19-specific CAR T-cell product.

Leukemia-free survival was significantly improved for patients with no history of HCT who received CD19 CAR T-cell therapy followed by consolidative HCT, Dr. Summers reported at the annual meeting of the American Society of Hematology.

However, the benefits of consolidative HCT are unclear for patients with a history of HCT, Dr. Summers said at the meeting, noting that larger studies are needed.

In her video interview at ASH 2018, Dr. Summers talked more about the challenges of late leukemic relapse and the potential role of HCT after CAR T-cell therapy.

Dr. Summers reported no disclosures related to her presentation.

SAN DIEGO – A hematopoietic cell transplant following chimeric antigen receptor (CAR) T-cell therapy for B-cell acute lymphocytic leukemia (B-ALL) may reduce late relapse risk in certain patients, a retrospective analysis suggests.

Corinne Summers, MD, of Seattle Children’s Hospital, and her colleagues evaluated the potential benefits of allogeneic hematopoietic cell transplant (HCT) in 50 pediatric and young adult B-ALL patients who had sustained leukemic remission after receiving SCRI-CAR19v1, a CD19-specific CAR T-cell product.

Leukemia-free survival was significantly improved for patients with no history of HCT who received CD19 CAR T-cell therapy followed by consolidative HCT, Dr. Summers reported at the annual meeting of the American Society of Hematology.

However, the benefits of consolidative HCT are unclear for patients with a history of HCT, Dr. Summers said at the meeting, noting that larger studies are needed.

In her video interview at ASH 2018, Dr. Summers talked more about the challenges of late leukemic relapse and the potential role of HCT after CAR T-cell therapy.

Dr. Summers reported no disclosures related to her presentation.

SAN DIEGO – A hematopoietic cell transplant following chimeric antigen receptor (CAR) T-cell therapy for B-cell acute lymphocytic leukemia (B-ALL) may reduce late relapse risk in certain patients, a retrospective analysis suggests.

Corinne Summers, MD, of Seattle Children’s Hospital, and her colleagues evaluated the potential benefits of allogeneic hematopoietic cell transplant (HCT) in 50 pediatric and young adult B-ALL patients who had sustained leukemic remission after receiving SCRI-CAR19v1, a CD19-specific CAR T-cell product.

Leukemia-free survival was significantly improved for patients with no history of HCT who received CD19 CAR T-cell therapy followed by consolidative HCT, Dr. Summers reported at the annual meeting of the American Society of Hematology.

However, the benefits of consolidative HCT are unclear for patients with a history of HCT, Dr. Summers said at the meeting, noting that larger studies are needed.

In her video interview at ASH 2018, Dr. Summers talked more about the challenges of late leukemic relapse and the potential role of HCT after CAR T-cell therapy.

Dr. Summers reported no disclosures related to her presentation.

SAN DIEGO – A novel myeloablative regimen along with familial haploidentical stem cell transplantation was well tolerated and cured 90% of 19 young patients with high-risk sickle cell disease who underwent the procedure, according to Mitchell S. Cairo, MD.

The approach involved parental donors who were partial matches (as opposed to human leukocyte antigen [HLA]–matched sibling donors), CD34 enrichment, and mononuclear cell add-back (2 x 10⁵ CD3/kg). The treatment resulted in a low cumulative incidence of acute and chronic graft-versus-host disease (6.2% and 6.7%, respectively) and stable to improved pulmonary and cardiac function. Patients also experienced significantly improved neurocognition and health-related quality of life at 2-year follow-up, Dr. Cairo of New York Medical College, Valhalla, reported at the annual meeting of the American Society of Hematology.

In a video interview, Dr. Cairo described the study, the potential benefits of familial haploidentical transplantation, and future directions.

“We have a 1-year 90% survival rate, and ... with a median follow-up now of 3 years with this approach, no patient has signs or symptoms of sickle cell disease,” he said. While the standard of care is “still to use an HLA-matched sibling donor that doesn’t have sickle cell disease,” this novel approach could benefit the five of six patients who don’t have such a donor.

The risks appear similar with the two approaches, but “more numbers will be needed to confirm this preliminary finding,” he said.

A second Food and Drug Administration–supported study with patients aged up to age 35 years (vs. 21 years in the current study) and with lower doses of the conditioning regimen to potentially reduce the risk of late adverse effects is underway, he said.

This study was supported by an FDA grant. Dr. Cairo reported receiving research funding from Janssen.

sworcester@mdedge.com

SAN DIEGO – A novel myeloablative regimen along with familial haploidentical stem cell transplantation was well tolerated and cured 90% of 19 young patients with high-risk sickle cell disease who underwent the procedure, according to Mitchell S. Cairo, MD.

The approach involved parental donors who were partial matches (as opposed to human leukocyte antigen [HLA]–matched sibling donors), CD34 enrichment, and mononuclear cell add-back (2 x 10⁵ CD3/kg). The treatment resulted in a low cumulative incidence of acute and chronic graft-versus-host disease (6.2% and 6.7%, respectively) and stable to improved pulmonary and cardiac function. Patients also experienced significantly improved neurocognition and health-related quality of life at 2-year follow-up, Dr. Cairo of New York Medical College, Valhalla, reported at the annual meeting of the American Society of Hematology.

In a video interview, Dr. Cairo described the study, the potential benefits of familial haploidentical transplantation, and future directions.

“We have a 1-year 90% survival rate, and ... with a median follow-up now of 3 years with this approach, no patient has signs or symptoms of sickle cell disease,” he said. While the standard of care is “still to use an HLA-matched sibling donor that doesn’t have sickle cell disease,” this novel approach could benefit the five of six patients who don’t have such a donor.

The risks appear similar with the two approaches, but “more numbers will be needed to confirm this preliminary finding,” he said.

A second Food and Drug Administration–supported study with patients aged up to age 35 years (vs. 21 years in the current study) and with lower doses of the conditioning regimen to potentially reduce the risk of late adverse effects is underway, he said.

This study was supported by an FDA grant. Dr. Cairo reported receiving research funding from Janssen.

sworcester@mdedge.com

SAN DIEGO – A novel myeloablative regimen along with familial haploidentical stem cell transplantation was well tolerated and cured 90% of 19 young patients with high-risk sickle cell disease who underwent the procedure, according to Mitchell S. Cairo, MD.

The approach involved parental donors who were partial matches (as opposed to human leukocyte antigen [HLA]–matched sibling donors), CD34 enrichment, and mononuclear cell add-back (2 x 10⁵ CD3/kg). The treatment resulted in a low cumulative incidence of acute and chronic graft-versus-host disease (6.2% and 6.7%, respectively) and stable to improved pulmonary and cardiac function. Patients also experienced significantly improved neurocognition and health-related quality of life at 2-year follow-up, Dr. Cairo of New York Medical College, Valhalla, reported at the annual meeting of the American Society of Hematology.

In a video interview, Dr. Cairo described the study, the potential benefits of familial haploidentical transplantation, and future directions.

“We have a 1-year 90% survival rate, and ... with a median follow-up now of 3 years with this approach, no patient has signs or symptoms of sickle cell disease,” he said. While the standard of care is “still to use an HLA-matched sibling donor that doesn’t have sickle cell disease,” this novel approach could benefit the five of six patients who don’t have such a donor.

The risks appear similar with the two approaches, but “more numbers will be needed to confirm this preliminary finding,” he said.

A second Food and Drug Administration–supported study with patients aged up to age 35 years (vs. 21 years in the current study) and with lower doses of the conditioning regimen to potentially reduce the risk of late adverse effects is underway, he said.

This study was supported by an FDA grant. Dr. Cairo reported receiving research funding from Janssen.

sworcester@mdedge.com

SAN DIEGO – Sickle cell research is booming after decades of stagnation, and talk of a cure is real, according to sickle cell disease expert Ifeyinwa (Ify) Osunkwo, MD.

“There is an opportunity to cure your disease no matter what age you are,” Dr. Osunkwo, medical director of the sickle cell program at Levine Cancer Institute at Atrium Health in Charlotte, N.C., said in a video interview at the annual meeting of the American Society of Hematology. “Sickle cell disease is now a disease of all ages and the treatments have to be treatments for everybody of all ages, not just for children.”

Dr. Osunkwo was the moderator of a press conference highlighting top research in sickle cell disease at ASH 2018. She pointed to findings from first-in-human trials of gene therapy using a lentiviral vector targeting BCL11A to reverse the sickle cell phenotype, as well as a study examining familial haploidentical stem cell transplantation with CD34 enrichment and mononuclear add-back in high-risk patients.

These two studies show parallel progress in curative therapies and are complementary, Dr. Osunkwo said. Improvements in transplants, and specifically in how patients are prepared and managed for them, will have a benefit in gene therapy.

But there are many other sickle cell disease studies being presented at ASH this year, she noted.

“There’s a recognition that sickle cell has been an understudied, underresourced, underexposed population,” she said. “And the suffering and the magnitude of medical problems is huge and it finally has bubbled up to the surface.”

Dr. Osunkwo reported being on advisory committees for Novartis and Pfizer and on the speaker’s bureau for Novartis. She has received honoraria from Terumo BCT and funding from the Health Resources and Services Administration and the Patient-Centered Outcomes Research Institute.

mschneider@mdedge.com

SAN DIEGO – Sickle cell research is booming after decades of stagnation, and talk of a cure is real, according to sickle cell disease expert Ifeyinwa (Ify) Osunkwo, MD.

“There is an opportunity to cure your disease no matter what age you are,” Dr. Osunkwo, medical director of the sickle cell program at Levine Cancer Institute at Atrium Health in Charlotte, N.C., said in a video interview at the annual meeting of the American Society of Hematology. “Sickle cell disease is now a disease of all ages and the treatments have to be treatments for everybody of all ages, not just for children.”

Dr. Osunkwo was the moderator of a press conference highlighting top research in sickle cell disease at ASH 2018. She pointed to findings from first-in-human trials of gene therapy using a lentiviral vector targeting BCL11A to reverse the sickle cell phenotype, as well as a study examining familial haploidentical stem cell transplantation with CD34 enrichment and mononuclear add-back in high-risk patients.

These two studies show parallel progress in curative therapies and are complementary, Dr. Osunkwo said. Improvements in transplants, and specifically in how patients are prepared and managed for them, will have a benefit in gene therapy.

But there are many other sickle cell disease studies being presented at ASH this year, she noted.

“There’s a recognition that sickle cell has been an understudied, underresourced, underexposed population,” she said. “And the suffering and the magnitude of medical problems is huge and it finally has bubbled up to the surface.”

Dr. Osunkwo reported being on advisory committees for Novartis and Pfizer and on the speaker’s bureau for Novartis. She has received honoraria from Terumo BCT and funding from the Health Resources and Services Administration and the Patient-Centered Outcomes Research Institute.

mschneider@mdedge.com

SAN DIEGO – Sickle cell research is booming after decades of stagnation, and talk of a cure is real, according to sickle cell disease expert Ifeyinwa (Ify) Osunkwo, MD.

“There is an opportunity to cure your disease no matter what age you are,” Dr. Osunkwo, medical director of the sickle cell program at Levine Cancer Institute at Atrium Health in Charlotte, N.C., said in a video interview at the annual meeting of the American Society of Hematology. “Sickle cell disease is now a disease of all ages and the treatments have to be treatments for everybody of all ages, not just for children.”

Dr. Osunkwo was the moderator of a press conference highlighting top research in sickle cell disease at ASH 2018. She pointed to findings from first-in-human trials of gene therapy using a lentiviral vector targeting BCL11A to reverse the sickle cell phenotype, as well as a study examining familial haploidentical stem cell transplantation with CD34 enrichment and mononuclear add-back in high-risk patients.

These two studies show parallel progress in curative therapies and are complementary, Dr. Osunkwo said. Improvements in transplants, and specifically in how patients are prepared and managed for them, will have a benefit in gene therapy.

But there are many other sickle cell disease studies being presented at ASH this year, she noted.

“There’s a recognition that sickle cell has been an understudied, underresourced, underexposed population,” she said. “And the suffering and the magnitude of medical problems is huge and it finally has bubbled up to the surface.”

Dr. Osunkwo reported being on advisory committees for Novartis and Pfizer and on the speaker’s bureau for Novartis. She has received honoraria from Terumo BCT and funding from the Health Resources and Services Administration and the Patient-Centered Outcomes Research Institute.

mschneider@mdedge.com

SAN DIEGO – Patients aged younger than 60 years with favorable-prognosis diffuse large B-cell lymphoma who were randomly assigned to therapy with four cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) had progression-free, event-free, and overall survival rates comparable with those of patients assigned to six cycles, investigators in the FLYER trial reported.

The four-cycle regimen was associated with a marked reduction in adverse events, with an overall drop in nonhematologic malignancies of approximately one-third compared with the six-cycle regimen.

For younger patients with favorable-prognosis DLBCL – defined as an age-adjusted International Prognostic Index score of 0 and low tumor burden (less than 7.5 cm) – four cycles of R-CHOP can be a new standard of care.

In this video interview at the annual meeting of the American Society of Hematology, Viola Poeschel, MD, of Saarland University in Homburg, Germany, describes the patient population who may benefit from shorter duration therapy.

SAN DIEGO – Patients aged younger than 60 years with favorable-prognosis diffuse large B-cell lymphoma who were randomly assigned to therapy with four cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) had progression-free, event-free, and overall survival rates comparable with those of patients assigned to six cycles, investigators in the FLYER trial reported.

The four-cycle regimen was associated with a marked reduction in adverse events, with an overall drop in nonhematologic malignancies of approximately one-third compared with the six-cycle regimen.

For younger patients with favorable-prognosis DLBCL – defined as an age-adjusted International Prognostic Index score of 0 and low tumor burden (less than 7.5 cm) – four cycles of R-CHOP can be a new standard of care.

In this video interview at the annual meeting of the American Society of Hematology, Viola Poeschel, MD, of Saarland University in Homburg, Germany, describes the patient population who may benefit from shorter duration therapy.

SAN DIEGO – Patients aged younger than 60 years with favorable-prognosis diffuse large B-cell lymphoma who were randomly assigned to therapy with four cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) had progression-free, event-free, and overall survival rates comparable with those of patients assigned to six cycles, investigators in the FLYER trial reported.

The four-cycle regimen was associated with a marked reduction in adverse events, with an overall drop in nonhematologic malignancies of approximately one-third compared with the six-cycle regimen.

For younger patients with favorable-prognosis DLBCL – defined as an age-adjusted International Prognostic Index score of 0 and low tumor burden (less than 7.5 cm) – four cycles of R-CHOP can be a new standard of care.

In this video interview at the annual meeting of the American Society of Hematology, Viola Poeschel, MD, of Saarland University in Homburg, Germany, describes the patient population who may benefit from shorter duration therapy.

SAN DIEGO – An adult with sickle cell disease has had significant remissions in symptoms and a near elimination of transfusion requirements after receiving an infusion of autologous stem cells genetically modified to simultaneously induce the fetal form of hemoglobin and decrease sickle hemoglobin.

In a first-in-human, proof-of-concept study, transduction of hematopoietic stem cells with a lentiviral vector targeted against the gamma globin repressor BCL11A in erythroid cells led to rapid induction of fetal hemoglobin and a reversal of the sickle cell disease (SCD) phenotype in the early phase of stem cell reconstitution, reported Erica B. Esrick, MD, from the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center in Boston.

“The potential advantage of this approach over the gene-addition strategy of gene therapy is that we can harness the physiologic switch machinery that exists in the cell to simultaneously increase fetal hemoglobin and decrease sickle hemoglobin,” she said at a briefing prior to her presentation at the annual meeting of the American Society of Hematology.

Several research groups are developing autologous gene therapy for beta-hemoglobinopathies, including the use of CRISPR-Cas9 technology to mimic a rare, naturally occurring mutation that causes the fetal type of hemoglobin to persist into adulthood in some patients with SCD and beta-thalassemia.

Dr. Esrick and her colleagues are trying a different approach: Using gene therapy to knock down BCL11A expression to induce gamma globin expression.

For the treatment, autologous hematopoietic stem cells are collected from patients following mobilization with plerixafor. The cells are then transduced with a lentiviral vector consisting of a novel short hairpin RNA embedded in an endogenous micro-RNA. The investigators refer to the construct as a shmiR (“schmeer”). The construct is designed to be erythroid specific, with BCL11A knocked down only in the red cell lineage, to avoid potential off-target effects of the therapy.

Following stem cell collection and transduction, patients undergo conditioning with busulfan prior to infusion of the modified stem cells.

In three patients treated thus far, the process has been shown to be highly efficient, with approximately 96% of treated cells transduced.

In the patient mentioned before, neutrophil engraftment was confirmed on day 22 after transfusion of the modified cells. He experienced adverse events that were consistent with myeloablative conditioning, but no adverse events associated with the modified cells.

During 6 months of follow-up the patient did not experience SCD-related pain, respiratory events, or neurologic events, and did not have anemia, with a total hemoglobin of 11 g/dL at 6 months. He has not required any transfusions since engraftment.

Patients in the trial will be followed for 2 years, and then will be enrolled in a 15-year follow-up study designed to evaluate the safety and the durability of therapy.

Dr. Esrick reported receiving honoraria from Bluebird Bio, maker of the short hairpin RNA construct used in the trial.

SOURCE: Esrick EB et al. ASH 2018, Abstract 1023.

SAN DIEGO – An adult with sickle cell disease has had significant remissions in symptoms and a near elimination of transfusion requirements after receiving an infusion of autologous stem cells genetically modified to simultaneously induce the fetal form of hemoglobin and decrease sickle hemoglobin.

In a first-in-human, proof-of-concept study, transduction of hematopoietic stem cells with a lentiviral vector targeted against the gamma globin repressor BCL11A in erythroid cells led to rapid induction of fetal hemoglobin and a reversal of the sickle cell disease (SCD) phenotype in the early phase of stem cell reconstitution, reported Erica B. Esrick, MD, from the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center in Boston.

“The potential advantage of this approach over the gene-addition strategy of gene therapy is that we can harness the physiologic switch machinery that exists in the cell to simultaneously increase fetal hemoglobin and decrease sickle hemoglobin,” she said at a briefing prior to her presentation at the annual meeting of the American Society of Hematology.

Several research groups are developing autologous gene therapy for beta-hemoglobinopathies, including the use of CRISPR-Cas9 technology to mimic a rare, naturally occurring mutation that causes the fetal type of hemoglobin to persist into adulthood in some patients with SCD and beta-thalassemia.

Dr. Esrick and her colleagues are trying a different approach: Using gene therapy to knock down BCL11A expression to induce gamma globin expression.

For the treatment, autologous hematopoietic stem cells are collected from patients following mobilization with plerixafor. The cells are then transduced with a lentiviral vector consisting of a novel short hairpin RNA embedded in an endogenous micro-RNA. The investigators refer to the construct as a shmiR (“schmeer”). The construct is designed to be erythroid specific, with BCL11A knocked down only in the red cell lineage, to avoid potential off-target effects of the therapy.

Following stem cell collection and transduction, patients undergo conditioning with busulfan prior to infusion of the modified stem cells.

In three patients treated thus far, the process has been shown to be highly efficient, with approximately 96% of treated cells transduced.

In the patient mentioned before, neutrophil engraftment was confirmed on day 22 after transfusion of the modified cells. He experienced adverse events that were consistent with myeloablative conditioning, but no adverse events associated with the modified cells.

During 6 months of follow-up the patient did not experience SCD-related pain, respiratory events, or neurologic events, and did not have anemia, with a total hemoglobin of 11 g/dL at 6 months. He has not required any transfusions since engraftment.

Patients in the trial will be followed for 2 years, and then will be enrolled in a 15-year follow-up study designed to evaluate the safety and the durability of therapy.

Dr. Esrick reported receiving honoraria from Bluebird Bio, maker of the short hairpin RNA construct used in the trial.

SOURCE: Esrick EB et al. ASH 2018, Abstract 1023.

SAN DIEGO – An adult with sickle cell disease has had significant remissions in symptoms and a near elimination of transfusion requirements after receiving an infusion of autologous stem cells genetically modified to simultaneously induce the fetal form of hemoglobin and decrease sickle hemoglobin.

In a first-in-human, proof-of-concept study, transduction of hematopoietic stem cells with a lentiviral vector targeted against the gamma globin repressor BCL11A in erythroid cells led to rapid induction of fetal hemoglobin and a reversal of the sickle cell disease (SCD) phenotype in the early phase of stem cell reconstitution, reported Erica B. Esrick, MD, from the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center in Boston.

“The potential advantage of this approach over the gene-addition strategy of gene therapy is that we can harness the physiologic switch machinery that exists in the cell to simultaneously increase fetal hemoglobin and decrease sickle hemoglobin,” she said at a briefing prior to her presentation at the annual meeting of the American Society of Hematology.

Several research groups are developing autologous gene therapy for beta-hemoglobinopathies, including the use of CRISPR-Cas9 technology to mimic a rare, naturally occurring mutation that causes the fetal type of hemoglobin to persist into adulthood in some patients with SCD and beta-thalassemia.

Dr. Esrick and her colleagues are trying a different approach: Using gene therapy to knock down BCL11A expression to induce gamma globin expression.

For the treatment, autologous hematopoietic stem cells are collected from patients following mobilization with plerixafor. The cells are then transduced with a lentiviral vector consisting of a novel short hairpin RNA embedded in an endogenous micro-RNA. The investigators refer to the construct as a shmiR (“schmeer”). The construct is designed to be erythroid specific, with BCL11A knocked down only in the red cell lineage, to avoid potential off-target effects of the therapy.

Following stem cell collection and transduction, patients undergo conditioning with busulfan prior to infusion of the modified stem cells.

In three patients treated thus far, the process has been shown to be highly efficient, with approximately 96% of treated cells transduced.

In the patient mentioned before, neutrophil engraftment was confirmed on day 22 after transfusion of the modified cells. He experienced adverse events that were consistent with myeloablative conditioning, but no adverse events associated with the modified cells.

During 6 months of follow-up the patient did not experience SCD-related pain, respiratory events, or neurologic events, and did not have anemia, with a total hemoglobin of 11 g/dL at 6 months. He has not required any transfusions since engraftment.

Patients in the trial will be followed for 2 years, and then will be enrolled in a 15-year follow-up study designed to evaluate the safety and the durability of therapy.

Dr. Esrick reported receiving honoraria from Bluebird Bio, maker of the short hairpin RNA construct used in the trial.

SOURCE: Esrick EB et al. ASH 2018, Abstract 1023.