ASH 2017

Maria-Victoria Mateos, MD, PhD

ATLANTA—Study results “strongly support” a new standard of care for transplant-ineligible patients with newly diagnosed multiple myeloma (MM), according to a speaker at the 2017 ASH Annual Meeting.

The study, ALCYONE, suggests treatment with bortezomib, melphalan, and prednisone (VMP) can be improved by the addition of daratumumab (D).

D-VMP produced deeper responses and prolonged progression-free survival (PFS) when compared to VMP.

“In this first phase 3, randomized study with a monoclonal antibody in newly diagnosed multiple myeloma, daratumumab reduced the risk of progression or death by 50%,” said Maria-Victoria Mateos, MD, PhD, of University Hospital of Salamanca in Spain.

“No new safety signals were observed [with D-VMP], except for higher infectious events that resolved. I would say the results of this study strongly support daratumumab in combination with VMP as a standard of care in transplant-ineligible, newly diagnosed multiple myeloma.”

Dr Mateos presented results from ALCYONE as a late-breaking abstract (LBA-4) at the ASH Annual Meeting. The study was simultaneously published in NEJM. The research was supported by Janssen Research and Development.

Patients and treatment

ALCYONE enrolled 706 patients with newly diagnosed MM who were not eligible for high-dose chemotherapy with autologous stem cell transplant.

Patients were randomized to receive VMP or D-VMP. They were stratified by International Staging System (I, II, III), region (Europe vs other), and age (<75 vs ≥75 years).

All patients received up to 9 cycles of VMP:

• Bortezomib at 1.3 mg/m² twice weekly on weeks 1, 2, 4, and 5 of cycle 1 and once weekly on weeks 1, 2, 4, and 5 of cycles 2 through 9
• Melphalan at 9 mg/m² once daily on days 1 to 4 of each cycle
• Prednisone at 60 mg/m² once daily on days 1 to 4 of each cycle.

Patients in the daratumumab arm received the drug at 16 mg/kg once-weekly for the first cycle, every 3 weeks for cycles 2 to 9, and every 4 weeks thereafter, until disease progression. These patients also received dexamethasone (to manage infusion reactions) at 20 mg on the same schedule.

Baseline characteristics were similar between the VMP (n=356) and D-VMP (n=350) arms. The median age was 71 in both arms (range, 50-91 in the VMP arm and 40-93 in the D-VMP arm). Males made up 47% of the VMP arm and 46% of the D-VMP arm.

Forty-nine percent of patients in the VMP arm and 52% in the D-VMP arm had an ECOG performance status of 1. Twenty-eight percent and 22%, respectively, had a status of 0.

The median follow-up was 16.5 months (range, 0.1-28.1). At the clinical cutoff date (June 12, 2017), 5% of patients in the VMP arm were still on study treatment, as were 71% of patients in the D-VMP arm.

Response and survival

“I would like to note that the benefit of the addition of daratumumab was observed since the beginning of the treatment,” Dr Mateos said.

The overall response rate was 74% in the VMP arm and 91% in the D-VMP arm (P<0.0001). The median duration of response was 21.3 months in the VMP arm and was not reached in the D-VMP arm.

The rate of complete response was 24% in the VMP arm and 43% in the D-VMP arm (P<0.0001). Six percent of patients in the VMP arm and 22% in the D-VMP arm were negative for minimal residual disease (P<0.0001).

The hazard ratio for disease progression or death in the D-VMP arm versus the VMP arm was 0.50 (P<0.0001).

The median PFS was 18.1 months in the VMP arm and was not reached in the D-VMP arm. The 12-month PFS was 76% and 87%, respectively. And the 18-month PFS was 50% and 72%, respectively.

D-VMP prolonged PFS regardless of patient sex, age, cytogenetic risk, ECOG performance status, baseline renal function, and other factors.

The median overall survival was not reached in either treatment arm. There were 48 deaths in the VMP arm and 45 in the D-VMP arm.

Adverse events

The most common treatment-emergent adverse events (TEAEs; in the D-VMP and VMP arms, respectively) were neutropenia (50% and 53%), thrombocytopenia (49% and 54%), anemia (28% and 38%), peripheral sensory neuropathy (28% and 34%), upper respiratory tract infection (26% and 14%), diarrhea (24% and 25%), pyrexia (23% and 21%), and nausea (21% and 22%).

The most common grade 3/4 TEAEs (in the D-VMP and VMP arms, respectively) were neutropenia (40% and 39%), thrombocytopenia (34% and 38%), and anemia (16% and 20%).

There were 6 deaths due to TEAEs in the D-VMP arm and 5 such deaths in the VMP arm.

The rate of grade 3/4 infections was higher in the D-VMP arm than the VMP arm—23% and 15%, respectively. The most common of these was pneumonia, with rates of 11% and 4%, respectively.

Infections resolved in 88% of cases in the D-VMP arm and 87% of cases in the VMP arm. Rates of treatment discontinuation due to infection were 0.9% and 1.4%, respectively. One patient in each group stopped treatment due to pneumonia.

Twenty-eight percent of patients in the D-VMP arm had infusion-related reactions (15% grade 3 and 2% grade 4). Most of these reactions occurred during the first infusion. Five patients (1.4%) discontinued daratumumab due to infusion-related reactions.

Maria-Victoria Mateos, MD, PhD

ATLANTA—Study results “strongly support” a new standard of care for transplant-ineligible patients with newly diagnosed multiple myeloma (MM), according to a speaker at the 2017 ASH Annual Meeting.

The study, ALCYONE, suggests treatment with bortezomib, melphalan, and prednisone (VMP) can be improved by the addition of daratumumab (D).

D-VMP produced deeper responses and prolonged progression-free survival (PFS) when compared to VMP.

“In this first phase 3, randomized study with a monoclonal antibody in newly diagnosed multiple myeloma, daratumumab reduced the risk of progression or death by 50%,” said Maria-Victoria Mateos, MD, PhD, of University Hospital of Salamanca in Spain.

“No new safety signals were observed [with D-VMP], except for higher infectious events that resolved. I would say the results of this study strongly support daratumumab in combination with VMP as a standard of care in transplant-ineligible, newly diagnosed multiple myeloma.”

Dr Mateos presented results from ALCYONE as a late-breaking abstract (LBA-4) at the ASH Annual Meeting. The study was simultaneously published in NEJM. The research was supported by Janssen Research and Development.

Patients and treatment

ALCYONE enrolled 706 patients with newly diagnosed MM who were not eligible for high-dose chemotherapy with autologous stem cell transplant.

Patients were randomized to receive VMP or D-VMP. They were stratified by International Staging System (I, II, III), region (Europe vs other), and age (<75 vs ≥75 years).

All patients received up to 9 cycles of VMP:

• Bortezomib at 1.3 mg/m² twice weekly on weeks 1, 2, 4, and 5 of cycle 1 and once weekly on weeks 1, 2, 4, and 5 of cycles 2 through 9
• Melphalan at 9 mg/m² once daily on days 1 to 4 of each cycle
• Prednisone at 60 mg/m² once daily on days 1 to 4 of each cycle.

Patients in the daratumumab arm received the drug at 16 mg/kg once-weekly for the first cycle, every 3 weeks for cycles 2 to 9, and every 4 weeks thereafter, until disease progression. These patients also received dexamethasone (to manage infusion reactions) at 20 mg on the same schedule.

Baseline characteristics were similar between the VMP (n=356) and D-VMP (n=350) arms. The median age was 71 in both arms (range, 50-91 in the VMP arm and 40-93 in the D-VMP arm). Males made up 47% of the VMP arm and 46% of the D-VMP arm.

Forty-nine percent of patients in the VMP arm and 52% in the D-VMP arm had an ECOG performance status of 1. Twenty-eight percent and 22%, respectively, had a status of 0.

The median follow-up was 16.5 months (range, 0.1-28.1). At the clinical cutoff date (June 12, 2017), 5% of patients in the VMP arm were still on study treatment, as were 71% of patients in the D-VMP arm.

Response and survival

“I would like to note that the benefit of the addition of daratumumab was observed since the beginning of the treatment,” Dr Mateos said.

The overall response rate was 74% in the VMP arm and 91% in the D-VMP arm (P<0.0001). The median duration of response was 21.3 months in the VMP arm and was not reached in the D-VMP arm.

The rate of complete response was 24% in the VMP arm and 43% in the D-VMP arm (P<0.0001). Six percent of patients in the VMP arm and 22% in the D-VMP arm were negative for minimal residual disease (P<0.0001).

The hazard ratio for disease progression or death in the D-VMP arm versus the VMP arm was 0.50 (P<0.0001).

The median PFS was 18.1 months in the VMP arm and was not reached in the D-VMP arm. The 12-month PFS was 76% and 87%, respectively. And the 18-month PFS was 50% and 72%, respectively.

D-VMP prolonged PFS regardless of patient sex, age, cytogenetic risk, ECOG performance status, baseline renal function, and other factors.

The median overall survival was not reached in either treatment arm. There were 48 deaths in the VMP arm and 45 in the D-VMP arm.

Adverse events

The most common treatment-emergent adverse events (TEAEs; in the D-VMP and VMP arms, respectively) were neutropenia (50% and 53%), thrombocytopenia (49% and 54%), anemia (28% and 38%), peripheral sensory neuropathy (28% and 34%), upper respiratory tract infection (26% and 14%), diarrhea (24% and 25%), pyrexia (23% and 21%), and nausea (21% and 22%).

The most common grade 3/4 TEAEs (in the D-VMP and VMP arms, respectively) were neutropenia (40% and 39%), thrombocytopenia (34% and 38%), and anemia (16% and 20%).

There were 6 deaths due to TEAEs in the D-VMP arm and 5 such deaths in the VMP arm.

The rate of grade 3/4 infections was higher in the D-VMP arm than the VMP arm—23% and 15%, respectively. The most common of these was pneumonia, with rates of 11% and 4%, respectively.

Infections resolved in 88% of cases in the D-VMP arm and 87% of cases in the VMP arm. Rates of treatment discontinuation due to infection were 0.9% and 1.4%, respectively. One patient in each group stopped treatment due to pneumonia.

Twenty-eight percent of patients in the D-VMP arm had infusion-related reactions (15% grade 3 and 2% grade 4). Most of these reactions occurred during the first infusion. Five patients (1.4%) discontinued daratumumab due to infusion-related reactions.

Maria-Victoria Mateos, MD, PhD

ATLANTA—Study results “strongly support” a new standard of care for transplant-ineligible patients with newly diagnosed multiple myeloma (MM), according to a speaker at the 2017 ASH Annual Meeting.

The study, ALCYONE, suggests treatment with bortezomib, melphalan, and prednisone (VMP) can be improved by the addition of daratumumab (D).

D-VMP produced deeper responses and prolonged progression-free survival (PFS) when compared to VMP.

“In this first phase 3, randomized study with a monoclonal antibody in newly diagnosed multiple myeloma, daratumumab reduced the risk of progression or death by 50%,” said Maria-Victoria Mateos, MD, PhD, of University Hospital of Salamanca in Spain.

“No new safety signals were observed [with D-VMP], except for higher infectious events that resolved. I would say the results of this study strongly support daratumumab in combination with VMP as a standard of care in transplant-ineligible, newly diagnosed multiple myeloma.”

Dr Mateos presented results from ALCYONE as a late-breaking abstract (LBA-4) at the ASH Annual Meeting. The study was simultaneously published in NEJM. The research was supported by Janssen Research and Development.

Patients and treatment

ALCYONE enrolled 706 patients with newly diagnosed MM who were not eligible for high-dose chemotherapy with autologous stem cell transplant.

Patients were randomized to receive VMP or D-VMP. They were stratified by International Staging System (I, II, III), region (Europe vs other), and age (<75 vs ≥75 years).

All patients received up to 9 cycles of VMP:

• Bortezomib at 1.3 mg/m² twice weekly on weeks 1, 2, 4, and 5 of cycle 1 and once weekly on weeks 1, 2, 4, and 5 of cycles 2 through 9
• Melphalan at 9 mg/m² once daily on days 1 to 4 of each cycle
• Prednisone at 60 mg/m² once daily on days 1 to 4 of each cycle.

Patients in the daratumumab arm received the drug at 16 mg/kg once-weekly for the first cycle, every 3 weeks for cycles 2 to 9, and every 4 weeks thereafter, until disease progression. These patients also received dexamethasone (to manage infusion reactions) at 20 mg on the same schedule.

Baseline characteristics were similar between the VMP (n=356) and D-VMP (n=350) arms. The median age was 71 in both arms (range, 50-91 in the VMP arm and 40-93 in the D-VMP arm). Males made up 47% of the VMP arm and 46% of the D-VMP arm.

Forty-nine percent of patients in the VMP arm and 52% in the D-VMP arm had an ECOG performance status of 1. Twenty-eight percent and 22%, respectively, had a status of 0.

The median follow-up was 16.5 months (range, 0.1-28.1). At the clinical cutoff date (June 12, 2017), 5% of patients in the VMP arm were still on study treatment, as were 71% of patients in the D-VMP arm.

Response and survival

“I would like to note that the benefit of the addition of daratumumab was observed since the beginning of the treatment,” Dr Mateos said.

The overall response rate was 74% in the VMP arm and 91% in the D-VMP arm (P<0.0001). The median duration of response was 21.3 months in the VMP arm and was not reached in the D-VMP arm.

The rate of complete response was 24% in the VMP arm and 43% in the D-VMP arm (P<0.0001). Six percent of patients in the VMP arm and 22% in the D-VMP arm were negative for minimal residual disease (P<0.0001).

The hazard ratio for disease progression or death in the D-VMP arm versus the VMP arm was 0.50 (P<0.0001).

The median PFS was 18.1 months in the VMP arm and was not reached in the D-VMP arm. The 12-month PFS was 76% and 87%, respectively. And the 18-month PFS was 50% and 72%, respectively.

D-VMP prolonged PFS regardless of patient sex, age, cytogenetic risk, ECOG performance status, baseline renal function, and other factors.

The median overall survival was not reached in either treatment arm. There were 48 deaths in the VMP arm and 45 in the D-VMP arm.

Adverse events

The most common treatment-emergent adverse events (TEAEs; in the D-VMP and VMP arms, respectively) were neutropenia (50% and 53%), thrombocytopenia (49% and 54%), anemia (28% and 38%), peripheral sensory neuropathy (28% and 34%), upper respiratory tract infection (26% and 14%), diarrhea (24% and 25%), pyrexia (23% and 21%), and nausea (21% and 22%).

The most common grade 3/4 TEAEs (in the D-VMP and VMP arms, respectively) were neutropenia (40% and 39%), thrombocytopenia (34% and 38%), and anemia (16% and 20%).

There were 6 deaths due to TEAEs in the D-VMP arm and 5 such deaths in the VMP arm.

The rate of grade 3/4 infections was higher in the D-VMP arm than the VMP arm—23% and 15%, respectively. The most common of these was pneumonia, with rates of 11% and 4%, respectively.

Infections resolved in 88% of cases in the D-VMP arm and 87% of cases in the VMP arm. Rates of treatment discontinuation due to infection were 0.9% and 1.4%, respectively. One patient in each group stopped treatment due to pneumonia.

Twenty-eight percent of patients in the D-VMP arm had infusion-related reactions (15% grade 3 and 2% grade 4). Most of these reactions occurred during the first infusion. Five patients (1.4%) discontinued daratumumab due to infusion-related reactions.

Atlanta – Adding caplacizumab, an anti–Von Willebrand Factor humanized single variable domain immunoglobulin, to standard therapy for acquired thrombotic thrombocytopenic purpura (aTTP) significantly hastened platelet normalization and improved several key clinical endpoints in a pivotal randomized placebo-controlled phase 3 trial of 145 patients (HERCULES).

At any given time, platelet normalization was 55% more likely with caplacizumab (10 mg) versus placebo (platelet normalization rate ratio, 1.55; 95% confidence interval, 1.10-2.20; P less than .01), Marie Scully, MD, reported in late-breaking oral presentation at the annual meeting of the American Society for Hematology.Caplacizumab also significantly reduced the rate of aTTP recurrence, compared with placebo (13% vs. 38%; P less than .001) and cut days of plasma exchange, plasma volume, and ICU and hospital stays by 31% to 65%, compared with placebo, reported Dr. Scully of University College Hospital, London, UK. HERCULES enrolled patients with an acute episode of aTTP and at least one prior plasma exchange (PE). Patients received caplacizumab (10 mg) or placebo plus daily PE plus corticosteroids. The caplacizumab group received a single IV dose before their first on-study PE followed by daily subcutaneous doses during PE therapy and for 30 days afterward.

Phase 2 data on aTTP earned caplacizumab fast track designation from the Food and Drug Administration in July 2017. In this video, Dr. Scully highlights key findings of the phase 3 HERCULES trial and discusses how physicians could integrate caplacizumab into their current aTTP treatment approach.

HERCULES was sponsored by Ablynx. Dr. Scully disclosed honoraria and research funding from Ablynx, Shire, Novartis, and Alexion.

Atlanta – Adding caplacizumab, an anti–Von Willebrand Factor humanized single variable domain immunoglobulin, to standard therapy for acquired thrombotic thrombocytopenic purpura (aTTP) significantly hastened platelet normalization and improved several key clinical endpoints in a pivotal randomized placebo-controlled phase 3 trial of 145 patients (HERCULES).

At any given time, platelet normalization was 55% more likely with caplacizumab (10 mg) versus placebo (platelet normalization rate ratio, 1.55; 95% confidence interval, 1.10-2.20; P less than .01), Marie Scully, MD, reported in late-breaking oral presentation at the annual meeting of the American Society for Hematology.Caplacizumab also significantly reduced the rate of aTTP recurrence, compared with placebo (13% vs. 38%; P less than .001) and cut days of plasma exchange, plasma volume, and ICU and hospital stays by 31% to 65%, compared with placebo, reported Dr. Scully of University College Hospital, London, UK. HERCULES enrolled patients with an acute episode of aTTP and at least one prior plasma exchange (PE). Patients received caplacizumab (10 mg) or placebo plus daily PE plus corticosteroids. The caplacizumab group received a single IV dose before their first on-study PE followed by daily subcutaneous doses during PE therapy and for 30 days afterward.

Phase 2 data on aTTP earned caplacizumab fast track designation from the Food and Drug Administration in July 2017. In this video, Dr. Scully highlights key findings of the phase 3 HERCULES trial and discusses how physicians could integrate caplacizumab into their current aTTP treatment approach.

HERCULES was sponsored by Ablynx. Dr. Scully disclosed honoraria and research funding from Ablynx, Shire, Novartis, and Alexion.

Atlanta – Adding caplacizumab, an anti–Von Willebrand Factor humanized single variable domain immunoglobulin, to standard therapy for acquired thrombotic thrombocytopenic purpura (aTTP) significantly hastened platelet normalization and improved several key clinical endpoints in a pivotal randomized placebo-controlled phase 3 trial of 145 patients (HERCULES).

At any given time, platelet normalization was 55% more likely with caplacizumab (10 mg) versus placebo (platelet normalization rate ratio, 1.55; 95% confidence interval, 1.10-2.20; P less than .01), Marie Scully, MD, reported in late-breaking oral presentation at the annual meeting of the American Society for Hematology.Caplacizumab also significantly reduced the rate of aTTP recurrence, compared with placebo (13% vs. 38%; P less than .001) and cut days of plasma exchange, plasma volume, and ICU and hospital stays by 31% to 65%, compared with placebo, reported Dr. Scully of University College Hospital, London, UK. HERCULES enrolled patients with an acute episode of aTTP and at least one prior plasma exchange (PE). Patients received caplacizumab (10 mg) or placebo plus daily PE plus corticosteroids. The caplacizumab group received a single IV dose before their first on-study PE followed by daily subcutaneous doses during PE therapy and for 30 days afterward.

Phase 2 data on aTTP earned caplacizumab fast track designation from the Food and Drug Administration in July 2017. In this video, Dr. Scully highlights key findings of the phase 3 HERCULES trial and discusses how physicians could integrate caplacizumab into their current aTTP treatment approach.

HERCULES was sponsored by Ablynx. Dr. Scully disclosed honoraria and research funding from Ablynx, Shire, Novartis, and Alexion.

ATLANTA – The rate of venous thromboembolism (VTE) in patients with non-Hodgkin lymphoma (NHL) treated with lenalidomide is similar to that seen in multiple myeloma, according to results of recent systematic review and meta-analysis of trials representing more than 10,000 treatment cycles.

Although rates of VTE for NHL and myeloma could not be directly compared statistically, the finding may have clinical implications for NHL patients, said lead study author Samuel Yamshon, MD, an internal medicine resident at Cornell University, New York.

“Although outpatient VTE prophylaxis is not currently recommended, it should be carefully considered in patients with lymphoma being treated with lenalidomide, especially those receiving lenalidomide as a single agent,” Dr. Yamshon said in a presentation of the results at the annual meeting of the American Society of Hematology.

The rate of thrombosis in patients with B cell NHL who received lenalidomide treatment was 0.75 events per 100 patient-cycles, according to results of the meta-analysis, which was based on 28 articles including 10,332 cycles of lenalidomide received by patients with B-cell NHL.

Reported rates of thrombosis in previously untreated myeloma patients treated with lenalidomide are between 0.7 and 0.8 per 100 patient-cycles, Dr. Yamshon said in his presentation.

Notably, single-agent lenalidomide was linked with a significantly increased risk of thrombosis compared with lenalidomide treatment in combinations. The relative risk of VTE for lenalidomide as a single agent versus lenalidomide in combination was 2.01 (95% confidence interval, 1.28-3.16; P = .002), according to the presented data.

The investigators were unsure why single-agent lenalidomide appeared to have caused increased rates of thrombosis compared to lenalidomide in combinations. “Perhaps patients treated with additional agents have a lower tumor burden, leading to less venous obstruction causing clots, or perhaps there’s a direct interaction between lenalidomide and tumor leading to effects on the vasculature and mediators of coagulation,” Dr. Yamshon said.

Chemotherapy and biologic combinations had somewhat different VTE rates when compared to single-agent lenalidomide. The rate in patients receiving lenalidomide alone was 1.06 events per 100 patient-cycles, compared with 0.73 and 0.41 events per 100 patient-cycles, respectively, for lenalidomide plus chemotherapy and lenalidomide plus biologics.

However, the lower event rate with lenalidomide and biologics compared with lenalidomide and chemotherapy was a “nonsignificant trend” that was likely caused by differences in patient characteristics between the two cohorts, according to Dr. Yamshon.

None of the studies included in the meta-analysis were prospectively designed to measure VTE as a primary or secondary outcome, Dr. Yamshon noted in a discussion of the study’s limitations.

Further studies are warranted to determine lenalidomide’s effect on the vasculature and how it effects mediators of coagulation, he added.

Based on the current results, Dr. Yamshon said it may be reasonable to consider VTE prophylaxis in NHL patients receiving lenalidomide.

“If we’re going to be recommending outpatient VTE prophylaxis in everyone on lenalidomide in multiple myeloma, and the rates (of VTE) are the same, I think it certainly makes sense based on the data to recommend it,” he said in a question-and-answer session.

Dr. Yamshon reported no conflicts related to the study. Coauthors reported disclosures related to Roche, Celgene, Seattle Genetics, Pharmacyclics, Cell Medica, Janssen, and AstraZeneca.

SOURCE: Yamshon S et al. Abstract 677.

ATLANTA – The rate of venous thromboembolism (VTE) in patients with non-Hodgkin lymphoma (NHL) treated with lenalidomide is similar to that seen in multiple myeloma, according to results of recent systematic review and meta-analysis of trials representing more than 10,000 treatment cycles.

Although rates of VTE for NHL and myeloma could not be directly compared statistically, the finding may have clinical implications for NHL patients, said lead study author Samuel Yamshon, MD, an internal medicine resident at Cornell University, New York.

“Although outpatient VTE prophylaxis is not currently recommended, it should be carefully considered in patients with lymphoma being treated with lenalidomide, especially those receiving lenalidomide as a single agent,” Dr. Yamshon said in a presentation of the results at the annual meeting of the American Society of Hematology.

The rate of thrombosis in patients with B cell NHL who received lenalidomide treatment was 0.75 events per 100 patient-cycles, according to results of the meta-analysis, which was based on 28 articles including 10,332 cycles of lenalidomide received by patients with B-cell NHL.

Reported rates of thrombosis in previously untreated myeloma patients treated with lenalidomide are between 0.7 and 0.8 per 100 patient-cycles, Dr. Yamshon said in his presentation.

Notably, single-agent lenalidomide was linked with a significantly increased risk of thrombosis compared with lenalidomide treatment in combinations. The relative risk of VTE for lenalidomide as a single agent versus lenalidomide in combination was 2.01 (95% confidence interval, 1.28-3.16; P = .002), according to the presented data.

The investigators were unsure why single-agent lenalidomide appeared to have caused increased rates of thrombosis compared to lenalidomide in combinations. “Perhaps patients treated with additional agents have a lower tumor burden, leading to less venous obstruction causing clots, or perhaps there’s a direct interaction between lenalidomide and tumor leading to effects on the vasculature and mediators of coagulation,” Dr. Yamshon said.

Chemotherapy and biologic combinations had somewhat different VTE rates when compared to single-agent lenalidomide. The rate in patients receiving lenalidomide alone was 1.06 events per 100 patient-cycles, compared with 0.73 and 0.41 events per 100 patient-cycles, respectively, for lenalidomide plus chemotherapy and lenalidomide plus biologics.

However, the lower event rate with lenalidomide and biologics compared with lenalidomide and chemotherapy was a “nonsignificant trend” that was likely caused by differences in patient characteristics between the two cohorts, according to Dr. Yamshon.

None of the studies included in the meta-analysis were prospectively designed to measure VTE as a primary or secondary outcome, Dr. Yamshon noted in a discussion of the study’s limitations.

Further studies are warranted to determine lenalidomide’s effect on the vasculature and how it effects mediators of coagulation, he added.

Based on the current results, Dr. Yamshon said it may be reasonable to consider VTE prophylaxis in NHL patients receiving lenalidomide.

“If we’re going to be recommending outpatient VTE prophylaxis in everyone on lenalidomide in multiple myeloma, and the rates (of VTE) are the same, I think it certainly makes sense based on the data to recommend it,” he said in a question-and-answer session.

Dr. Yamshon reported no conflicts related to the study. Coauthors reported disclosures related to Roche, Celgene, Seattle Genetics, Pharmacyclics, Cell Medica, Janssen, and AstraZeneca.

SOURCE: Yamshon S et al. Abstract 677.

ATLANTA – The rate of venous thromboembolism (VTE) in patients with non-Hodgkin lymphoma (NHL) treated with lenalidomide is similar to that seen in multiple myeloma, according to results of recent systematic review and meta-analysis of trials representing more than 10,000 treatment cycles.

Although rates of VTE for NHL and myeloma could not be directly compared statistically, the finding may have clinical implications for NHL patients, said lead study author Samuel Yamshon, MD, an internal medicine resident at Cornell University, New York.

“Although outpatient VTE prophylaxis is not currently recommended, it should be carefully considered in patients with lymphoma being treated with lenalidomide, especially those receiving lenalidomide as a single agent,” Dr. Yamshon said in a presentation of the results at the annual meeting of the American Society of Hematology.

The rate of thrombosis in patients with B cell NHL who received lenalidomide treatment was 0.75 events per 100 patient-cycles, according to results of the meta-analysis, which was based on 28 articles including 10,332 cycles of lenalidomide received by patients with B-cell NHL.

Reported rates of thrombosis in previously untreated myeloma patients treated with lenalidomide are between 0.7 and 0.8 per 100 patient-cycles, Dr. Yamshon said in his presentation.

Notably, single-agent lenalidomide was linked with a significantly increased risk of thrombosis compared with lenalidomide treatment in combinations. The relative risk of VTE for lenalidomide as a single agent versus lenalidomide in combination was 2.01 (95% confidence interval, 1.28-3.16; P = .002), according to the presented data.

The investigators were unsure why single-agent lenalidomide appeared to have caused increased rates of thrombosis compared to lenalidomide in combinations. “Perhaps patients treated with additional agents have a lower tumor burden, leading to less venous obstruction causing clots, or perhaps there’s a direct interaction between lenalidomide and tumor leading to effects on the vasculature and mediators of coagulation,” Dr. Yamshon said.

Chemotherapy and biologic combinations had somewhat different VTE rates when compared to single-agent lenalidomide. The rate in patients receiving lenalidomide alone was 1.06 events per 100 patient-cycles, compared with 0.73 and 0.41 events per 100 patient-cycles, respectively, for lenalidomide plus chemotherapy and lenalidomide plus biologics.

However, the lower event rate with lenalidomide and biologics compared with lenalidomide and chemotherapy was a “nonsignificant trend” that was likely caused by differences in patient characteristics between the two cohorts, according to Dr. Yamshon.

None of the studies included in the meta-analysis were prospectively designed to measure VTE as a primary or secondary outcome, Dr. Yamshon noted in a discussion of the study’s limitations.

Further studies are warranted to determine lenalidomide’s effect on the vasculature and how it effects mediators of coagulation, he added.

Based on the current results, Dr. Yamshon said it may be reasonable to consider VTE prophylaxis in NHL patients receiving lenalidomide.

“If we’re going to be recommending outpatient VTE prophylaxis in everyone on lenalidomide in multiple myeloma, and the rates (of VTE) are the same, I think it certainly makes sense based on the data to recommend it,” he said in a question-and-answer session.

Dr. Yamshon reported no conflicts related to the study. Coauthors reported disclosures related to Roche, Celgene, Seattle Genetics, Pharmacyclics, Cell Medica, Janssen, and AstraZeneca.

SOURCE: Yamshon S et al. Abstract 677.

ATLANTA – Twelve months of daily treatment with the novel oral factor Xa inhibitor edoxaban was noninferior to standard subcutaneous therapy with dalteparin for treatment of venous thromboembolism in patients with cancer, according to late-breaking results from a randomized, open-label, blinded-outcomes trial.

Throughout follow-up, trial arms had nearly identical rates of survival free from recurrent VTE or major bleeding, Gary E. Raskob, PhD, reported during a late-breaking oral presentation at the annual meeting of the American Society of Hematology. “Edoxaban was associated with a lower rate of recurrent VTE, which was offset by a similar increase in risk of major bleeding,” he said. “Therefore, oral edoxaban was noninferior to subcutaneous dalteparin for the [combined] primary outcome.”

Venous thromboembolism affects about one in five patients with active cancer and is difficult to treat because patients face increased risks of recurrence and bleeding. The struggle to balance these risks fuels morbidity and mortality and can hamper cancer treatment, said Dr. Raskob of the University of Oklahoma, Oklahoma City.

Pharmacy and medical oncology societies recommend long-term low-molecular-weight heparin for cancer patients with VTE, but the daily burden of subcutaneous injections leads many to stop after about 2-4 months of treatment, Dr. Raskob said. “Direct oral anticoagulants may be an attractive alternative.”

For the trial, 1,446 adults with cancer and lower limb VTE from 114 clinics in North America, Europe, Australia, and New Zealand received either edoxaban (60 mg daily) or dalteparin (200 IU/kg for 30 days, followed by 150 IU/kg) for up to 12 months. Nearly all patients had active cancer. Tumor types reflected what’s most common in practice, such as malignancies of the lung, colon, and breast. About 50 patients had primary or metastatic brain cancers. Approximately two-thirds had pulmonary embolism with or without deep-vein thrombosis, while the rest had isolated deep-vein thrombosis.

After 12 months of follow-up, 12.8% of edoxaban patients had at least one recurrence of VTE or a major bleed, compared with 13.5% of dalteparin patients (hazard ratio, 0.97; 95% confidence interval, 0.70-1.36; P = .006 for noninferiority). Edoxaban also was noninferior to dalteparin after the first 6 months of treatment and in the per-protocol analysis (HRs, 1.0; P = .02 for noninferiority in each analysis). Thus, differences in efficacy did not only reflect better compliance to oral therapy, Dr. Raskob said.

He also reported on individual outcomes. In all, 10.3% of dalteparin recipients had a VTE recurrence, as did 6.5% of edoxaban recipients, for a risk difference of 3.8% (95% CI, 7.1%-0.4%). More than half of recurrences in each group were symptomatic, and none were fatal. Bleeding caused no deaths in either study arm, and each therapy conferred an identical chance of a grade 3-4 major bleed (2.3%).

Edoxaban was associated, however, with a greater frequency of major bleeds (33 events; 6.3%) than was dalteparin (17 events; 3.2%; risk difference, 3.1%; 95% CI, 0.5%-5.7%). In particular, patients who received edoxaban had a slightly higher rate of upper gastrointestinal bleeds. Most had gastric cancer.

Future studies should evaluate whether these patients should receive a lower dose of edoxaban, said Dr. Raskob. “We don’t yet fully know the minimum effective dose [of edoxaban] in cancer patients.”

He also addressed the idea that heparin has antineoplastic activity, calling it “one we should probably abandon. The concept originates from older trials in which researchers probably did not recognize that heparin was preventing fatal pulmonary embolism, he said.

The investigators soon will begin deeper analyses that should inform patient selection, he said. For now, he recommends discussing these findings with patients to help them make an informed choice between oral anticoagulation, with its ease of use but slightly higher rate of major bleeds, and subcutaneous heparin, with its lower bleeding rate and treatment burden.

Daiichi Sankyo provided funding. Dr. Raskob disclosed consulting relationships and honoraria from Daiichi Sankyo, Eli Lilly, Janssen, and several other pharmaceutical companies.

SOURCE: Raskob G et al. ASH Abstract LBA-6.

ATLANTA – Twelve months of daily treatment with the novel oral factor Xa inhibitor edoxaban was noninferior to standard subcutaneous therapy with dalteparin for treatment of venous thromboembolism in patients with cancer, according to late-breaking results from a randomized, open-label, blinded-outcomes trial.

Throughout follow-up, trial arms had nearly identical rates of survival free from recurrent VTE or major bleeding, Gary E. Raskob, PhD, reported during a late-breaking oral presentation at the annual meeting of the American Society of Hematology. “Edoxaban was associated with a lower rate of recurrent VTE, which was offset by a similar increase in risk of major bleeding,” he said. “Therefore, oral edoxaban was noninferior to subcutaneous dalteparin for the [combined] primary outcome.”

Venous thromboembolism affects about one in five patients with active cancer and is difficult to treat because patients face increased risks of recurrence and bleeding. The struggle to balance these risks fuels morbidity and mortality and can hamper cancer treatment, said Dr. Raskob of the University of Oklahoma, Oklahoma City.

Pharmacy and medical oncology societies recommend long-term low-molecular-weight heparin for cancer patients with VTE, but the daily burden of subcutaneous injections leads many to stop after about 2-4 months of treatment, Dr. Raskob said. “Direct oral anticoagulants may be an attractive alternative.”

For the trial, 1,446 adults with cancer and lower limb VTE from 114 clinics in North America, Europe, Australia, and New Zealand received either edoxaban (60 mg daily) or dalteparin (200 IU/kg for 30 days, followed by 150 IU/kg) for up to 12 months. Nearly all patients had active cancer. Tumor types reflected what’s most common in practice, such as malignancies of the lung, colon, and breast. About 50 patients had primary or metastatic brain cancers. Approximately two-thirds had pulmonary embolism with or without deep-vein thrombosis, while the rest had isolated deep-vein thrombosis.

After 12 months of follow-up, 12.8% of edoxaban patients had at least one recurrence of VTE or a major bleed, compared with 13.5% of dalteparin patients (hazard ratio, 0.97; 95% confidence interval, 0.70-1.36; P = .006 for noninferiority). Edoxaban also was noninferior to dalteparin after the first 6 months of treatment and in the per-protocol analysis (HRs, 1.0; P = .02 for noninferiority in each analysis). Thus, differences in efficacy did not only reflect better compliance to oral therapy, Dr. Raskob said.

He also reported on individual outcomes. In all, 10.3% of dalteparin recipients had a VTE recurrence, as did 6.5% of edoxaban recipients, for a risk difference of 3.8% (95% CI, 7.1%-0.4%). More than half of recurrences in each group were symptomatic, and none were fatal. Bleeding caused no deaths in either study arm, and each therapy conferred an identical chance of a grade 3-4 major bleed (2.3%).

Edoxaban was associated, however, with a greater frequency of major bleeds (33 events; 6.3%) than was dalteparin (17 events; 3.2%; risk difference, 3.1%; 95% CI, 0.5%-5.7%). In particular, patients who received edoxaban had a slightly higher rate of upper gastrointestinal bleeds. Most had gastric cancer.

Future studies should evaluate whether these patients should receive a lower dose of edoxaban, said Dr. Raskob. “We don’t yet fully know the minimum effective dose [of edoxaban] in cancer patients.”

He also addressed the idea that heparin has antineoplastic activity, calling it “one we should probably abandon. The concept originates from older trials in which researchers probably did not recognize that heparin was preventing fatal pulmonary embolism, he said.

The investigators soon will begin deeper analyses that should inform patient selection, he said. For now, he recommends discussing these findings with patients to help them make an informed choice between oral anticoagulation, with its ease of use but slightly higher rate of major bleeds, and subcutaneous heparin, with its lower bleeding rate and treatment burden.

Daiichi Sankyo provided funding. Dr. Raskob disclosed consulting relationships and honoraria from Daiichi Sankyo, Eli Lilly, Janssen, and several other pharmaceutical companies.

SOURCE: Raskob G et al. ASH Abstract LBA-6.

ATLANTA – Twelve months of daily treatment with the novel oral factor Xa inhibitor edoxaban was noninferior to standard subcutaneous therapy with dalteparin for treatment of venous thromboembolism in patients with cancer, according to late-breaking results from a randomized, open-label, blinded-outcomes trial.

Throughout follow-up, trial arms had nearly identical rates of survival free from recurrent VTE or major bleeding, Gary E. Raskob, PhD, reported during a late-breaking oral presentation at the annual meeting of the American Society of Hematology. “Edoxaban was associated with a lower rate of recurrent VTE, which was offset by a similar increase in risk of major bleeding,” he said. “Therefore, oral edoxaban was noninferior to subcutaneous dalteparin for the [combined] primary outcome.”

Venous thromboembolism affects about one in five patients with active cancer and is difficult to treat because patients face increased risks of recurrence and bleeding. The struggle to balance these risks fuels morbidity and mortality and can hamper cancer treatment, said Dr. Raskob of the University of Oklahoma, Oklahoma City.

Pharmacy and medical oncology societies recommend long-term low-molecular-weight heparin for cancer patients with VTE, but the daily burden of subcutaneous injections leads many to stop after about 2-4 months of treatment, Dr. Raskob said. “Direct oral anticoagulants may be an attractive alternative.”

For the trial, 1,446 adults with cancer and lower limb VTE from 114 clinics in North America, Europe, Australia, and New Zealand received either edoxaban (60 mg daily) or dalteparin (200 IU/kg for 30 days, followed by 150 IU/kg) for up to 12 months. Nearly all patients had active cancer. Tumor types reflected what’s most common in practice, such as malignancies of the lung, colon, and breast. About 50 patients had primary or metastatic brain cancers. Approximately two-thirds had pulmonary embolism with or without deep-vein thrombosis, while the rest had isolated deep-vein thrombosis.

After 12 months of follow-up, 12.8% of edoxaban patients had at least one recurrence of VTE or a major bleed, compared with 13.5% of dalteparin patients (hazard ratio, 0.97; 95% confidence interval, 0.70-1.36; P = .006 for noninferiority). Edoxaban also was noninferior to dalteparin after the first 6 months of treatment and in the per-protocol analysis (HRs, 1.0; P = .02 for noninferiority in each analysis). Thus, differences in efficacy did not only reflect better compliance to oral therapy, Dr. Raskob said.

He also reported on individual outcomes. In all, 10.3% of dalteparin recipients had a VTE recurrence, as did 6.5% of edoxaban recipients, for a risk difference of 3.8% (95% CI, 7.1%-0.4%). More than half of recurrences in each group were symptomatic, and none were fatal. Bleeding caused no deaths in either study arm, and each therapy conferred an identical chance of a grade 3-4 major bleed (2.3%).

Edoxaban was associated, however, with a greater frequency of major bleeds (33 events; 6.3%) than was dalteparin (17 events; 3.2%; risk difference, 3.1%; 95% CI, 0.5%-5.7%). In particular, patients who received edoxaban had a slightly higher rate of upper gastrointestinal bleeds. Most had gastric cancer.

Future studies should evaluate whether these patients should receive a lower dose of edoxaban, said Dr. Raskob. “We don’t yet fully know the minimum effective dose [of edoxaban] in cancer patients.”

He also addressed the idea that heparin has antineoplastic activity, calling it “one we should probably abandon. The concept originates from older trials in which researchers probably did not recognize that heparin was preventing fatal pulmonary embolism, he said.

The investigators soon will begin deeper analyses that should inform patient selection, he said. For now, he recommends discussing these findings with patients to help them make an informed choice between oral anticoagulation, with its ease of use but slightly higher rate of major bleeds, and subcutaneous heparin, with its lower bleeding rate and treatment burden.

Daiichi Sankyo provided funding. Dr. Raskob disclosed consulting relationships and honoraria from Daiichi Sankyo, Eli Lilly, Janssen, and several other pharmaceutical companies.

SOURCE: Raskob G et al. ASH Abstract LBA-6.

ATLANTA – Relapsed or refractory chronic lymphocytic leukemia (CLL) often has a suboptimal response to conventional chemotherapy, because of adverse biological features that can accumulate in cells.

The combination of bendamustine (Treanda) and rituximab has been associated with about 60% overall responses rates, median progression-free survival of approximately 15 months, and overall survival of nearly 3 years in patients with CLL, and there is now evidence that substituting venetoclax (Venclexta) for bendamustine could improve outcomes even further.

In a video interview at the annual meeting of the American Society of Hematology, John F. Seymour, MBBS, PhD, discussed results from a planned interim analysis of the phase 3 MURANO study comparing bendamustine plus rituximab with venetoclax plus rituximab in patients with relapsed/refractory CLL.

Venetoclax/rituximab was superior to bendamustine/rituximab for prolonging progression-free survival, with effects consistent across subgroups, regardless of mutation status, and for having a clinically meaningful improvement in overall survival.

The MURANO trial was funded by AbbVie. Dr. Seymour reported honoraria, research funding, and advisory committee and speakers bureau participation for AbbVie and other companies.

ATLANTA – Relapsed or refractory chronic lymphocytic leukemia (CLL) often has a suboptimal response to conventional chemotherapy, because of adverse biological features that can accumulate in cells.

The combination of bendamustine (Treanda) and rituximab has been associated with about 60% overall responses rates, median progression-free survival of approximately 15 months, and overall survival of nearly 3 years in patients with CLL, and there is now evidence that substituting venetoclax (Venclexta) for bendamustine could improve outcomes even further.

In a video interview at the annual meeting of the American Society of Hematology, John F. Seymour, MBBS, PhD, discussed results from a planned interim analysis of the phase 3 MURANO study comparing bendamustine plus rituximab with venetoclax plus rituximab in patients with relapsed/refractory CLL.

Venetoclax/rituximab was superior to bendamustine/rituximab for prolonging progression-free survival, with effects consistent across subgroups, regardless of mutation status, and for having a clinically meaningful improvement in overall survival.

The MURANO trial was funded by AbbVie. Dr. Seymour reported honoraria, research funding, and advisory committee and speakers bureau participation for AbbVie and other companies.

ATLANTA – Relapsed or refractory chronic lymphocytic leukemia (CLL) often has a suboptimal response to conventional chemotherapy, because of adverse biological features that can accumulate in cells.

The combination of bendamustine (Treanda) and rituximab has been associated with about 60% overall responses rates, median progression-free survival of approximately 15 months, and overall survival of nearly 3 years in patients with CLL, and there is now evidence that substituting venetoclax (Venclexta) for bendamustine could improve outcomes even further.

In a video interview at the annual meeting of the American Society of Hematology, John F. Seymour, MBBS, PhD, discussed results from a planned interim analysis of the phase 3 MURANO study comparing bendamustine plus rituximab with venetoclax plus rituximab in patients with relapsed/refractory CLL.

Venetoclax/rituximab was superior to bendamustine/rituximab for prolonging progression-free survival, with effects consistent across subgroups, regardless of mutation status, and for having a clinically meaningful improvement in overall survival.

The MURANO trial was funded by AbbVie. Dr. Seymour reported honoraria, research funding, and advisory committee and speakers bureau participation for AbbVie and other companies.

ATLANTA – The VMP regimen, consisting of bortezomib, melphalan, and prednisone, is a standard of care in Europe for frontline therapy for patients with multiple myeloma who, for reasons of age or infirmity, are not good candidates for autologous stem cell transplant.

In this video interview at the annual meeting of the American Society of Hematology, Jesus San-Miguel, MD, of the Clinical University of Navarra in Pamplona, Spain, discusses the results of the phase 3 international ALCYONE trial, comparing VMP with the same regimen plus the addition of the anti-CD38 monoclonal antibody daratumumab (Darzalex).

Adding daratumumab to VMP regimen as first-line therapy for 706 patients with multiple myeloma cut in half the risk of disease progression or death and substantially improved the rate of minimal residual disease negativity, Dr. San-Miguel reported. There were no new safety signals from adding the monoclonal antibody to VMP.

The ALCYONE study was supported by Janssen Research & Development. Dr. San-Miguel reported serving as an adviser to the company and several others.

ATLANTA – The VMP regimen, consisting of bortezomib, melphalan, and prednisone, is a standard of care in Europe for frontline therapy for patients with multiple myeloma who, for reasons of age or infirmity, are not good candidates for autologous stem cell transplant.

In this video interview at the annual meeting of the American Society of Hematology, Jesus San-Miguel, MD, of the Clinical University of Navarra in Pamplona, Spain, discusses the results of the phase 3 international ALCYONE trial, comparing VMP with the same regimen plus the addition of the anti-CD38 monoclonal antibody daratumumab (Darzalex).

Adding daratumumab to VMP regimen as first-line therapy for 706 patients with multiple myeloma cut in half the risk of disease progression or death and substantially improved the rate of minimal residual disease negativity, Dr. San-Miguel reported. There were no new safety signals from adding the monoclonal antibody to VMP.

The ALCYONE study was supported by Janssen Research & Development. Dr. San-Miguel reported serving as an adviser to the company and several others.

ATLANTA – The VMP regimen, consisting of bortezomib, melphalan, and prednisone, is a standard of care in Europe for frontline therapy for patients with multiple myeloma who, for reasons of age or infirmity, are not good candidates for autologous stem cell transplant.

In this video interview at the annual meeting of the American Society of Hematology, Jesus San-Miguel, MD, of the Clinical University of Navarra in Pamplona, Spain, discusses the results of the phase 3 international ALCYONE trial, comparing VMP with the same regimen plus the addition of the anti-CD38 monoclonal antibody daratumumab (Darzalex).

Adding daratumumab to VMP regimen as first-line therapy for 706 patients with multiple myeloma cut in half the risk of disease progression or death and substantially improved the rate of minimal residual disease negativity, Dr. San-Miguel reported. There were no new safety signals from adding the monoclonal antibody to VMP.

The ALCYONE study was supported by Janssen Research & Development. Dr. San-Miguel reported serving as an adviser to the company and several others.

ATLANTA – Adding the anti-CD38 monoclonal antibody daratumumab (Darzalex) to the standard VMP regimen as first-line therapy for patients with multiple myeloma cut in half the risk of disease progression or death and substantially improved the rate of minimal residual disease (MRD) negativity, investigators in the ALCYONE trial reported.

Neil Osterweil/ Frontline Medical News

SOURCE: Mateos MV et al. ASH Abstract LBA-4.

ATLANTA – Adding the anti-CD38 monoclonal antibody daratumumab (Darzalex) to the standard VMP regimen as first-line therapy for patients with multiple myeloma cut in half the risk of disease progression or death and substantially improved the rate of minimal residual disease (MRD) negativity, investigators in the ALCYONE trial reported.

Neil Osterweil/ Frontline Medical News

SOURCE: Mateos MV et al. ASH Abstract LBA-4.

ATLANTA – Adding the anti-CD38 monoclonal antibody daratumumab (Darzalex) to the standard VMP regimen as first-line therapy for patients with multiple myeloma cut in half the risk of disease progression or death and substantially improved the rate of minimal residual disease (MRD) negativity, investigators in the ALCYONE trial reported.

Neil Osterweil/ Frontline Medical News

SOURCE: Mateos MV et al. ASH Abstract LBA-4.

Photo courtesy of ASH

ATLANTA—Updated results from the HAVEN 2 trial have shown that emicizumab prophylaxis can reduce bleeds in children with hemophilia A and factor VIII inhibitors.

Sixty-five percent of all patients enrolled in HAVEN 2 had no bleeds while on emicizumab, and 95% had no treated bleeds.

Among patients who had been on emicizumab for at least 12 weeks, 35% had no bleeds, and 87% had no treated bleeds.

The most common adverse events (AEs) in this trial were viral upper respiratory tract infections and injection site reactions.

Guy Young, MD, of Children’s Hospital Los Angeles in California, presented these results at the 2017 ASH Annual Meeting (abstract 85). The trial was sponsored by Hoffmann-La Roche.

HAVEN 2 enrolled 60 patients, ages 1 to 17, who had hemophilia A and inhibitors. Most patients (95%) had severe hemophilia, 3.3% (n=2) had mild disease, and 1.7% (n=1) had moderate disease.

Nearly a quarter of patients (73.3%) had previously received prophylaxis, and 26.7% had previously received episodic treatment.

The median number of bleeds in the previous 24 weeks was 6.0 (range, 0-155), and 38.3% of patients had target joints.

Patients received emicizumab prophylaxis at 3 mg/kg/week for 4 weeks and 1.5 mg/kg/week thereafter. The median observation time was 9 weeks (range, 1.6 to 41.6 weeks).

Efficacy

The efficacy analysis included 57 patients who were younger than 12. The 3 older patients were only included in the safety analysis.

Of the 57 patients, 64.9% had 0 bleeds, 94.7% had 0 treated bleeds, and 98.2% had 0 treated spontaneous bleeds and 0 treated joint bleeds. None of the patients had treated target joint bleeds.

There were a total of 65 bleeds in 20 patients. Eight were joint bleeds, 2 were muscle bleeds, and the rest were classified as “other.” Of the 55 “other’’ bleeds, 26 (40.0%) were spontaneous, 36 (55.4%) were traumatic, and 3 (4.6%) were due to a procedure/surgery.

A subset of 23 patients received emicizumab for at least 12 weeks. They had a median treatment duration of 38.1 weeks (range, 12.7 to 41.6 weeks).

Of these patients, 34.8% had 0 bleeds, 87.0% had 0 treated bleeds, and 95.7% had 0 treated spontaneous bleeds and 0 treated joint bleeds. There were a total of 41 bleeds in 15 of these patients. Three bleeds (joint, muscle, and hip) were treated.

The median annualized bleeding rate (ABR) for the 23 patients was 1.5 for all bleeds and 0.0 for all types of treated bleeds.

There were 13 patients who had participated in a non-interventional study prior to enrolling in HAVEN 2, so these patients could serve as their own controls. The patients had an overall reduction in ABR of 99% with emicizumab.

Safety

All 60 patients were evaluated for safety. Forty patients had a total of 201 AEs. The most common AEs were viral upper respiratory tract infection (16.7%) and injection site reactions (16.7%)

There were 7 serious AEs in 6 patients—muscle hemorrhage (n=2), eye pain, catheter site injection, device-related infection, mouth hemorrhage, and appendicitis. None of these events were considered treatment-related.

There were no thromboembolic or thrombotic microangiopathy events, and none of the patients tested positive for anti-drug antibodies.

“The safety profile of emicizumab was favorable and well-tolerated,” Dr Young said. “And these updated results from the HAVEN 2 study confirm our prior efficacy results, presented at ISTH, that emicizumab successfully prevents or reduces bleeds.”

Photo courtesy of ASH

ATLANTA—Updated results from the HAVEN 2 trial have shown that emicizumab prophylaxis can reduce bleeds in children with hemophilia A and factor VIII inhibitors.

Sixty-five percent of all patients enrolled in HAVEN 2 had no bleeds while on emicizumab, and 95% had no treated bleeds.

Among patients who had been on emicizumab for at least 12 weeks, 35% had no bleeds, and 87% had no treated bleeds.

The most common adverse events (AEs) in this trial were viral upper respiratory tract infections and injection site reactions.

Guy Young, MD, of Children’s Hospital Los Angeles in California, presented these results at the 2017 ASH Annual Meeting (abstract 85). The trial was sponsored by Hoffmann-La Roche.

HAVEN 2 enrolled 60 patients, ages 1 to 17, who had hemophilia A and inhibitors. Most patients (95%) had severe hemophilia, 3.3% (n=2) had mild disease, and 1.7% (n=1) had moderate disease.

Nearly a quarter of patients (73.3%) had previously received prophylaxis, and 26.7% had previously received episodic treatment.

The median number of bleeds in the previous 24 weeks was 6.0 (range, 0-155), and 38.3% of patients had target joints.

Patients received emicizumab prophylaxis at 3 mg/kg/week for 4 weeks and 1.5 mg/kg/week thereafter. The median observation time was 9 weeks (range, 1.6 to 41.6 weeks).

Efficacy

The efficacy analysis included 57 patients who were younger than 12. The 3 older patients were only included in the safety analysis.

Of the 57 patients, 64.9% had 0 bleeds, 94.7% had 0 treated bleeds, and 98.2% had 0 treated spontaneous bleeds and 0 treated joint bleeds. None of the patients had treated target joint bleeds.

There were a total of 65 bleeds in 20 patients. Eight were joint bleeds, 2 were muscle bleeds, and the rest were classified as “other.” Of the 55 “other’’ bleeds, 26 (40.0%) were spontaneous, 36 (55.4%) were traumatic, and 3 (4.6%) were due to a procedure/surgery.

A subset of 23 patients received emicizumab for at least 12 weeks. They had a median treatment duration of 38.1 weeks (range, 12.7 to 41.6 weeks).

Of these patients, 34.8% had 0 bleeds, 87.0% had 0 treated bleeds, and 95.7% had 0 treated spontaneous bleeds and 0 treated joint bleeds. There were a total of 41 bleeds in 15 of these patients. Three bleeds (joint, muscle, and hip) were treated.

The median annualized bleeding rate (ABR) for the 23 patients was 1.5 for all bleeds and 0.0 for all types of treated bleeds.

There were 13 patients who had participated in a non-interventional study prior to enrolling in HAVEN 2, so these patients could serve as their own controls. The patients had an overall reduction in ABR of 99% with emicizumab.

Safety

All 60 patients were evaluated for safety. Forty patients had a total of 201 AEs. The most common AEs were viral upper respiratory tract infection (16.7%) and injection site reactions (16.7%)

There were 7 serious AEs in 6 patients—muscle hemorrhage (n=2), eye pain, catheter site injection, device-related infection, mouth hemorrhage, and appendicitis. None of these events were considered treatment-related.

There were no thromboembolic or thrombotic microangiopathy events, and none of the patients tested positive for anti-drug antibodies.

“The safety profile of emicizumab was favorable and well-tolerated,” Dr Young said. “And these updated results from the HAVEN 2 study confirm our prior efficacy results, presented at ISTH, that emicizumab successfully prevents or reduces bleeds.”

Photo courtesy of ASH

ATLANTA—Updated results from the HAVEN 2 trial have shown that emicizumab prophylaxis can reduce bleeds in children with hemophilia A and factor VIII inhibitors.

Sixty-five percent of all patients enrolled in HAVEN 2 had no bleeds while on emicizumab, and 95% had no treated bleeds.

Among patients who had been on emicizumab for at least 12 weeks, 35% had no bleeds, and 87% had no treated bleeds.

The most common adverse events (AEs) in this trial were viral upper respiratory tract infections and injection site reactions.

Guy Young, MD, of Children’s Hospital Los Angeles in California, presented these results at the 2017 ASH Annual Meeting (abstract 85). The trial was sponsored by Hoffmann-La Roche.

HAVEN 2 enrolled 60 patients, ages 1 to 17, who had hemophilia A and inhibitors. Most patients (95%) had severe hemophilia, 3.3% (n=2) had mild disease, and 1.7% (n=1) had moderate disease.

Nearly a quarter of patients (73.3%) had previously received prophylaxis, and 26.7% had previously received episodic treatment.

The median number of bleeds in the previous 24 weeks was 6.0 (range, 0-155), and 38.3% of patients had target joints.

Patients received emicizumab prophylaxis at 3 mg/kg/week for 4 weeks and 1.5 mg/kg/week thereafter. The median observation time was 9 weeks (range, 1.6 to 41.6 weeks).

Efficacy

The efficacy analysis included 57 patients who were younger than 12. The 3 older patients were only included in the safety analysis.

Of the 57 patients, 64.9% had 0 bleeds, 94.7% had 0 treated bleeds, and 98.2% had 0 treated spontaneous bleeds and 0 treated joint bleeds. None of the patients had treated target joint bleeds.

There were a total of 65 bleeds in 20 patients. Eight were joint bleeds, 2 were muscle bleeds, and the rest were classified as “other.” Of the 55 “other’’ bleeds, 26 (40.0%) were spontaneous, 36 (55.4%) were traumatic, and 3 (4.6%) were due to a procedure/surgery.

A subset of 23 patients received emicizumab for at least 12 weeks. They had a median treatment duration of 38.1 weeks (range, 12.7 to 41.6 weeks).

Of these patients, 34.8% had 0 bleeds, 87.0% had 0 treated bleeds, and 95.7% had 0 treated spontaneous bleeds and 0 treated joint bleeds. There were a total of 41 bleeds in 15 of these patients. Three bleeds (joint, muscle, and hip) were treated.

The median annualized bleeding rate (ABR) for the 23 patients was 1.5 for all bleeds and 0.0 for all types of treated bleeds.

There were 13 patients who had participated in a non-interventional study prior to enrolling in HAVEN 2, so these patients could serve as their own controls. The patients had an overall reduction in ABR of 99% with emicizumab.

Safety

All 60 patients were evaluated for safety. Forty patients had a total of 201 AEs. The most common AEs were viral upper respiratory tract infection (16.7%) and injection site reactions (16.7%)

There were 7 serious AEs in 6 patients—muscle hemorrhage (n=2), eye pain, catheter site injection, device-related infection, mouth hemorrhage, and appendicitis. None of these events were considered treatment-related.

There were no thromboembolic or thrombotic microangiopathy events, and none of the patients tested positive for anti-drug antibodies.

“The safety profile of emicizumab was favorable and well-tolerated,” Dr Young said. “And these updated results from the HAVEN 2 study confirm our prior efficacy results, presented at ISTH, that emicizumab successfully prevents or reduces bleeds.”

ATLANTA – In older patients with acute myeloid leukemia (AML) in complete remission after intensive chemotherapy, the addition of maintenance therapy with azacitidine significantly improved disease-free survival (DFS), according to results of a randomized, placebo-controlled phase 3 study.

Compared with observation, DFS was significantly improved in the maintenance azacitidine arm, according to results from the 116-patient HOVON97 trial presented at the annual meeting of the American Society of Hematology.

Overall survival was not significantly different between arms, possibly because of an excess of allogeneic transplant in the observation arm, according to Geert Huls, MD, PhD, of the department of hematology, University Medical Center Groningen, the Netherlands.

“When censored for allogeneic transplant, maintenance with azacitidine improves overall survival,” Dr. Huls said during an oral presentation on the findings.

The randomized maintenance therapy trial was designed to include 126 patients aged 60 years or older who had a confirmed diagnosis of AML and refractory anemia with excess of blasts (RAEB, RAEB-t) and who were in complete remission or in complete remission with incomplete blood count recovery after two cycles of therapy.

Investigators randomly assigned 116 patients to maintenance versus observation. Researchers intended to assign a total of 126 patients, but the trial was stopped early because of slow accrual, Dr. Huls said.

Maintenance treatment with azacitidine was given until relapse for no more than 12 cycles, according to the study protocol. Disease-free survival, the primary endpoint, was measured from the date of randomization to relapse or death from any cause.

Azacitidine maintenance therapy significantly improved DFS (P = .03), Dr. Huls said. After researchers adjusted for poor risk cytogenetic abnormalities at diagnosis and platelet count at study entry, the DFS difference remained significant (hazard ratio, 0.61; 95% confidence interval, 0.4-0.92; P = .019).

Overall survival, a secondary endpoint of the trial, was not significantly different between arms, even after adjustment for cytogenetic abnormalities and platelet counts, Dr. Huls said.

However, investigators found an excess of allogeneic transplant in the observation arm (11 patients, vs. 3 in the azacitidine arm). After they censored those 14 patients, they saw a difference in overall survival favoring azacitidine maintenance that approached significance (P = .07).

Dr. Huls speculated that the excess of transplant may have been related to “the psychology of the doctors.” In the maintenance arm, the physician’s thought process may have been that “ ‘this patient has now had two lines of treatment and has a relapse, and we are done,’ and in the [observation] arm he says, ‘well, the patient has had one arm of treatment, let’s go for another,’ ” Dr. Huls said.

Tolerability data showed that 14 adverse events were reported in the azacitidine maintenance arm, versus 4 for observation. One serious adverse event of grade 3 was reported in the azacitidine arm. The proportion of patients without platelet transfusions during the study was 86% for azacitidine and 93% for observation, and the proportion of patients without red blood cell transfusions was similarly 86% and 92% for the azacitidine and observation arms, respectively.

Dr. Huls reported financial relationships with Janssen and Celgene.

SOURCE: Huls G et al. ASH 2017 Abstract 463.

ATLANTA – In older patients with acute myeloid leukemia (AML) in complete remission after intensive chemotherapy, the addition of maintenance therapy with azacitidine significantly improved disease-free survival (DFS), according to results of a randomized, placebo-controlled phase 3 study.

Compared with observation, DFS was significantly improved in the maintenance azacitidine arm, according to results from the 116-patient HOVON97 trial presented at the annual meeting of the American Society of Hematology.

Overall survival was not significantly different between arms, possibly because of an excess of allogeneic transplant in the observation arm, according to Geert Huls, MD, PhD, of the department of hematology, University Medical Center Groningen, the Netherlands.

“When censored for allogeneic transplant, maintenance with azacitidine improves overall survival,” Dr. Huls said during an oral presentation on the findings.

The randomized maintenance therapy trial was designed to include 126 patients aged 60 years or older who had a confirmed diagnosis of AML and refractory anemia with excess of blasts (RAEB, RAEB-t) and who were in complete remission or in complete remission with incomplete blood count recovery after two cycles of therapy.

Investigators randomly assigned 116 patients to maintenance versus observation. Researchers intended to assign a total of 126 patients, but the trial was stopped early because of slow accrual, Dr. Huls said.

Maintenance treatment with azacitidine was given until relapse for no more than 12 cycles, according to the study protocol. Disease-free survival, the primary endpoint, was measured from the date of randomization to relapse or death from any cause.

Azacitidine maintenance therapy significantly improved DFS (P = .03), Dr. Huls said. After researchers adjusted for poor risk cytogenetic abnormalities at diagnosis and platelet count at study entry, the DFS difference remained significant (hazard ratio, 0.61; 95% confidence interval, 0.4-0.92; P = .019).

Overall survival, a secondary endpoint of the trial, was not significantly different between arms, even after adjustment for cytogenetic abnormalities and platelet counts, Dr. Huls said.

However, investigators found an excess of allogeneic transplant in the observation arm (11 patients, vs. 3 in the azacitidine arm). After they censored those 14 patients, they saw a difference in overall survival favoring azacitidine maintenance that approached significance (P = .07).

Dr. Huls speculated that the excess of transplant may have been related to “the psychology of the doctors.” In the maintenance arm, the physician’s thought process may have been that “ ‘this patient has now had two lines of treatment and has a relapse, and we are done,’ and in the [observation] arm he says, ‘well, the patient has had one arm of treatment, let’s go for another,’ ” Dr. Huls said.

Tolerability data showed that 14 adverse events were reported in the azacitidine maintenance arm, versus 4 for observation. One serious adverse event of grade 3 was reported in the azacitidine arm. The proportion of patients without platelet transfusions during the study was 86% for azacitidine and 93% for observation, and the proportion of patients without red blood cell transfusions was similarly 86% and 92% for the azacitidine and observation arms, respectively.

Dr. Huls reported financial relationships with Janssen and Celgene.

SOURCE: Huls G et al. ASH 2017 Abstract 463.

ATLANTA – In older patients with acute myeloid leukemia (AML) in complete remission after intensive chemotherapy, the addition of maintenance therapy with azacitidine significantly improved disease-free survival (DFS), according to results of a randomized, placebo-controlled phase 3 study.

Compared with observation, DFS was significantly improved in the maintenance azacitidine arm, according to results from the 116-patient HOVON97 trial presented at the annual meeting of the American Society of Hematology.

Overall survival was not significantly different between arms, possibly because of an excess of allogeneic transplant in the observation arm, according to Geert Huls, MD, PhD, of the department of hematology, University Medical Center Groningen, the Netherlands.

“When censored for allogeneic transplant, maintenance with azacitidine improves overall survival,” Dr. Huls said during an oral presentation on the findings.

The randomized maintenance therapy trial was designed to include 126 patients aged 60 years or older who had a confirmed diagnosis of AML and refractory anemia with excess of blasts (RAEB, RAEB-t) and who were in complete remission or in complete remission with incomplete blood count recovery after two cycles of therapy.

Investigators randomly assigned 116 patients to maintenance versus observation. Researchers intended to assign a total of 126 patients, but the trial was stopped early because of slow accrual, Dr. Huls said.

Maintenance treatment with azacitidine was given until relapse for no more than 12 cycles, according to the study protocol. Disease-free survival, the primary endpoint, was measured from the date of randomization to relapse or death from any cause.

Azacitidine maintenance therapy significantly improved DFS (P = .03), Dr. Huls said. After researchers adjusted for poor risk cytogenetic abnormalities at diagnosis and platelet count at study entry, the DFS difference remained significant (hazard ratio, 0.61; 95% confidence interval, 0.4-0.92; P = .019).

Overall survival, a secondary endpoint of the trial, was not significantly different between arms, even after adjustment for cytogenetic abnormalities and platelet counts, Dr. Huls said.

However, investigators found an excess of allogeneic transplant in the observation arm (11 patients, vs. 3 in the azacitidine arm). After they censored those 14 patients, they saw a difference in overall survival favoring azacitidine maintenance that approached significance (P = .07).

Dr. Huls speculated that the excess of transplant may have been related to “the psychology of the doctors.” In the maintenance arm, the physician’s thought process may have been that “ ‘this patient has now had two lines of treatment and has a relapse, and we are done,’ and in the [observation] arm he says, ‘well, the patient has had one arm of treatment, let’s go for another,’ ” Dr. Huls said.

Tolerability data showed that 14 adverse events were reported in the azacitidine maintenance arm, versus 4 for observation. One serious adverse event of grade 3 was reported in the azacitidine arm. The proportion of patients without platelet transfusions during the study was 86% for azacitidine and 93% for observation, and the proportion of patients without red blood cell transfusions was similarly 86% and 92% for the azacitidine and observation arms, respectively.

Dr. Huls reported financial relationships with Janssen and Celgene.

SOURCE: Huls G et al. ASH 2017 Abstract 463.

ATLANTA – In the ZUMA-1 trial, more than one-third of patients with refractory large B-cell lymphomas treated with the chimeric antigen receptor (CAR) T-cell product axicabtagene ciloleucel (Yescarta; axi-cel) had durable responses, with some patients having complete responses lasting more than 1 year after a single infusion.

Updated combined phase 1 and 2 results in 108 patients with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, or transformed follicular lymphoma showed an objective response rate of 82% of patients – including 58% showing complete responses – after a median follow-up of 15.4 months.

In a video interview at the annual meeting of the American Society of Hematology, Sattva S. Neelapu, MD, from the University of Texas MD Anderson Cancer Center in Houston discusses the use of CAR T cells directed against the CD19 antigen in patients with relapsed/refractory B-cell lymphomas and describes efforts to improve responses while managing adverse events common to CAR T-cell therapies, notably cytokine release syndrome.

ZUMA-1 is supported by Kite Pharma, which developed axicabtagene ciloleucel, and the Leukemia & Lymphoma Society’s Therapy Acceleration Program. Dr. Neelapu reported receiving advisory board fees from the company.

ATLANTA – In the ZUMA-1 trial, more than one-third of patients with refractory large B-cell lymphomas treated with the chimeric antigen receptor (CAR) T-cell product axicabtagene ciloleucel (Yescarta; axi-cel) had durable responses, with some patients having complete responses lasting more than 1 year after a single infusion.

Updated combined phase 1 and 2 results in 108 patients with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, or transformed follicular lymphoma showed an objective response rate of 82% of patients – including 58% showing complete responses – after a median follow-up of 15.4 months.

In a video interview at the annual meeting of the American Society of Hematology, Sattva S. Neelapu, MD, from the University of Texas MD Anderson Cancer Center in Houston discusses the use of CAR T cells directed against the CD19 antigen in patients with relapsed/refractory B-cell lymphomas and describes efforts to improve responses while managing adverse events common to CAR T-cell therapies, notably cytokine release syndrome.

ZUMA-1 is supported by Kite Pharma, which developed axicabtagene ciloleucel, and the Leukemia & Lymphoma Society’s Therapy Acceleration Program. Dr. Neelapu reported receiving advisory board fees from the company.

ATLANTA – In the ZUMA-1 trial, more than one-third of patients with refractory large B-cell lymphomas treated with the chimeric antigen receptor (CAR) T-cell product axicabtagene ciloleucel (Yescarta; axi-cel) had durable responses, with some patients having complete responses lasting more than 1 year after a single infusion.

Updated combined phase 1 and 2 results in 108 patients with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, or transformed follicular lymphoma showed an objective response rate of 82% of patients – including 58% showing complete responses – after a median follow-up of 15.4 months.

In a video interview at the annual meeting of the American Society of Hematology, Sattva S. Neelapu, MD, from the University of Texas MD Anderson Cancer Center in Houston discusses the use of CAR T cells directed against the CD19 antigen in patients with relapsed/refractory B-cell lymphomas and describes efforts to improve responses while managing adverse events common to CAR T-cell therapies, notably cytokine release syndrome.

ZUMA-1 is supported by Kite Pharma, which developed axicabtagene ciloleucel, and the Leukemia & Lymphoma Society’s Therapy Acceleration Program. Dr. Neelapu reported receiving advisory board fees from the company.