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Luspatercept appears safe, effective in β-thalassemia
MADRID—Results of a phase 2 study have shown that luspatercept can produce sustained increases in hemoglobin and reductions in transfusion burden in adults with β-thalassemia.
Some patients are still receiving the drug and experiencing clinical benefits beyond 24 months.
Luspatercept has been well-tolerated in these patients, producing no serious adverse events (AEs).
“Luspatercept has many characteristics that are promising . . .,” said Antonio G. Piga, MD, of Turin University in Turin, Italy.
He presented results of the phase 2 study at the 22nd Congress of the European Hematology Association (EHA) as abstract S129.
The study was sponsored by Celgene in collaboration with Acceleron Pharma.
Dr Piga presented data on 63 patients—32 of whom were transfusion-dependent (TD) and 31 of whom were non-transfusion-dependent (NTD).
For the entire study cohort, the median age was 38 (range, 20-62), 52% of patients were male, and 67% had undergone a splenectomy.
In the NTD patients, the median hemoglobin at baseline was 8.5 g/dL (range, 6.5-9.8).
The TD patients received a median of 8 (range, 4-18) red blood cell (RBC) units every 12 weeks.
For the 3-month base study, patients received luspatercept at 0.2 mg/kg to 1.25 mg/kg every 3 weeks.
In the ongoing extension study, patients can receive luspatercept at 0.8 mg/kg to 1.25 mg/kg every 3 weeks for up to 5 years.
Efficacy in NTD patients
The median duration of treatment for NTD patients (n=31) was 18.6 months (range, 1.3-29.4 months; ongoing).
Over a 12-week period, 71% (22/31) of NTD patients saw at least a 1.0 g/dL increase in mean hemoglobin from baseline. Fifty-two percent (16/31) saw an increase of 1.5 g/dL or greater.
To assess quality of life in NTD patients, the researchers used FACIT-F, a 13-item questionnaire used to assess anemia-related symptoms such as fatigue and weakness.
Fifty-eight percent (7/12) of patients with a baseline FACIT-F deficit (<44 points) had improved by at least 3 points at 48 weeks.
And 86% (6/7) of patients with at least a 3-point increase in FACIT-F score had at least a 1.0 g/dL improvement in mean hemoglobin over a 12-week period.
Efficacy in TD patients
The median duration of treatment for TD patients was 14.2 months (range, 0.7-27.2 months, ongoing).
Seventy-eight percent (25/32) of these patients had at least a 20% reduction in RBC units transfused from 12 weeks pre-treatment to any 12-week interval on treatment. Sixty-nine percent (22/32) had at least a 33% reduction at any 12-week interval.
Fifty percent of patients (12/24) who received an estimated 6 to 20 RBC units every 24 weeks achieved a reduction in transfusion burden from baseline of at least 33% in the fixed 12-week interval from weeks 13 to 24.
Forty-six percent (11/24) achieved a reduction in transfusion burden from baseline of at least 33% in the interval from weeks 37 to 48.
Safety
The most common AEs possibly or probably related to luspatercept were bone pain (38%), headache (28%), myalgia (22%), arthralgia (19%), musculoskeletal pain (17%), asthenia (14%), injection site pain (13%), and back pain (11%).
Most AEs were grade 1 or 2 in severity. Treatment-related grade 3 AEs included bone pain (n=3), asthenia (n=2), and headache (n=1).
Dr Piga said these results support an ongoing phase 3 study of luspatercept in regularly transfused patients with β-thalassemia (BELIEVE, NCT02604433), which recently completed enrollment. 
MADRID—Results of a phase 2 study have shown that luspatercept can produce sustained increases in hemoglobin and reductions in transfusion burden in adults with β-thalassemia.
Some patients are still receiving the drug and experiencing clinical benefits beyond 24 months.
Luspatercept has been well-tolerated in these patients, producing no serious adverse events (AEs).
“Luspatercept has many characteristics that are promising . . .,” said Antonio G. Piga, MD, of Turin University in Turin, Italy.
He presented results of the phase 2 study at the 22nd Congress of the European Hematology Association (EHA) as abstract S129.
The study was sponsored by Celgene in collaboration with Acceleron Pharma.
Dr Piga presented data on 63 patients—32 of whom were transfusion-dependent (TD) and 31 of whom were non-transfusion-dependent (NTD).
For the entire study cohort, the median age was 38 (range, 20-62), 52% of patients were male, and 67% had undergone a splenectomy.
In the NTD patients, the median hemoglobin at baseline was 8.5 g/dL (range, 6.5-9.8).
The TD patients received a median of 8 (range, 4-18) red blood cell (RBC) units every 12 weeks.
For the 3-month base study, patients received luspatercept at 0.2 mg/kg to 1.25 mg/kg every 3 weeks.
In the ongoing extension study, patients can receive luspatercept at 0.8 mg/kg to 1.25 mg/kg every 3 weeks for up to 5 years.
Efficacy in NTD patients
The median duration of treatment for NTD patients (n=31) was 18.6 months (range, 1.3-29.4 months; ongoing).
Over a 12-week period, 71% (22/31) of NTD patients saw at least a 1.0 g/dL increase in mean hemoglobin from baseline. Fifty-two percent (16/31) saw an increase of 1.5 g/dL or greater.
To assess quality of life in NTD patients, the researchers used FACIT-F, a 13-item questionnaire used to assess anemia-related symptoms such as fatigue and weakness.
Fifty-eight percent (7/12) of patients with a baseline FACIT-F deficit (<44 points) had improved by at least 3 points at 48 weeks.
And 86% (6/7) of patients with at least a 3-point increase in FACIT-F score had at least a 1.0 g/dL improvement in mean hemoglobin over a 12-week period.
Efficacy in TD patients
The median duration of treatment for TD patients was 14.2 months (range, 0.7-27.2 months, ongoing).
Seventy-eight percent (25/32) of these patients had at least a 20% reduction in RBC units transfused from 12 weeks pre-treatment to any 12-week interval on treatment. Sixty-nine percent (22/32) had at least a 33% reduction at any 12-week interval.
Fifty percent of patients (12/24) who received an estimated 6 to 20 RBC units every 24 weeks achieved a reduction in transfusion burden from baseline of at least 33% in the fixed 12-week interval from weeks 13 to 24.
Forty-six percent (11/24) achieved a reduction in transfusion burden from baseline of at least 33% in the interval from weeks 37 to 48.
Safety
The most common AEs possibly or probably related to luspatercept were bone pain (38%), headache (28%), myalgia (22%), arthralgia (19%), musculoskeletal pain (17%), asthenia (14%), injection site pain (13%), and back pain (11%).
Most AEs were grade 1 or 2 in severity. Treatment-related grade 3 AEs included bone pain (n=3), asthenia (n=2), and headache (n=1).
Dr Piga said these results support an ongoing phase 3 study of luspatercept in regularly transfused patients with β-thalassemia (BELIEVE, NCT02604433), which recently completed enrollment.
MADRID—Results of a phase 2 study have shown that luspatercept can produce sustained increases in hemoglobin and reductions in transfusion burden in adults with β-thalassemia.
Some patients are still receiving the drug and experiencing clinical benefits beyond 24 months.
Luspatercept has been well-tolerated in these patients, producing no serious adverse events (AEs).
“Luspatercept has many characteristics that are promising . . .,” said Antonio G. Piga, MD, of Turin University in Turin, Italy.
He presented results of the phase 2 study at the 22nd Congress of the European Hematology Association (EHA) as abstract S129.
The study was sponsored by Celgene in collaboration with Acceleron Pharma.
Dr Piga presented data on 63 patients—32 of whom were transfusion-dependent (TD) and 31 of whom were non-transfusion-dependent (NTD).
For the entire study cohort, the median age was 38 (range, 20-62), 52% of patients were male, and 67% had undergone a splenectomy.
In the NTD patients, the median hemoglobin at baseline was 8.5 g/dL (range, 6.5-9.8).
The TD patients received a median of 8 (range, 4-18) red blood cell (RBC) units every 12 weeks.
For the 3-month base study, patients received luspatercept at 0.2 mg/kg to 1.25 mg/kg every 3 weeks.
In the ongoing extension study, patients can receive luspatercept at 0.8 mg/kg to 1.25 mg/kg every 3 weeks for up to 5 years.
Efficacy in NTD patients
The median duration of treatment for NTD patients (n=31) was 18.6 months (range, 1.3-29.4 months; ongoing).
Over a 12-week period, 71% (22/31) of NTD patients saw at least a 1.0 g/dL increase in mean hemoglobin from baseline. Fifty-two percent (16/31) saw an increase of 1.5 g/dL or greater.
To assess quality of life in NTD patients, the researchers used FACIT-F, a 13-item questionnaire used to assess anemia-related symptoms such as fatigue and weakness.
Fifty-eight percent (7/12) of patients with a baseline FACIT-F deficit (<44 points) had improved by at least 3 points at 48 weeks.
And 86% (6/7) of patients with at least a 3-point increase in FACIT-F score had at least a 1.0 g/dL improvement in mean hemoglobin over a 12-week period.
Efficacy in TD patients
The median duration of treatment for TD patients was 14.2 months (range, 0.7-27.2 months, ongoing).
Seventy-eight percent (25/32) of these patients had at least a 20% reduction in RBC units transfused from 12 weeks pre-treatment to any 12-week interval on treatment. Sixty-nine percent (22/32) had at least a 33% reduction at any 12-week interval.
Fifty percent of patients (12/24) who received an estimated 6 to 20 RBC units every 24 weeks achieved a reduction in transfusion burden from baseline of at least 33% in the fixed 12-week interval from weeks 13 to 24.
Forty-six percent (11/24) achieved a reduction in transfusion burden from baseline of at least 33% in the interval from weeks 37 to 48.
Safety
The most common AEs possibly or probably related to luspatercept were bone pain (38%), headache (28%), myalgia (22%), arthralgia (19%), musculoskeletal pain (17%), asthenia (14%), injection site pain (13%), and back pain (11%).
Most AEs were grade 1 or 2 in severity. Treatment-related grade 3 AEs included bone pain (n=3), asthenia (n=2), and headache (n=1).
Dr Piga said these results support an ongoing phase 3 study of luspatercept in regularly transfused patients with β-thalassemia (BELIEVE, NCT02604433), which recently completed enrollment.
Nivolumab for long-term treatment of cHL after auto-HSCT
LUGANO, SWITZERLAND—Nivolumab can provide long-term treatment for a broad range of adults who have relapsed or refractory classical Hodgkin lymphoma (cHL) after autologous hematopoietic stem cell transplant (auto-HSCT), according to a presentation at the 14th International Conference on Malignant Lymphoma (ICML).
In the phase 2 CheckMate-205 study, cHL patients achieved durable responses regardless of the depth of response, previous exposure to brentuximab vedotin (BV), and refractoriness to prior therapies.
Researchers observed sustained progression-free survival (PFS) in patients with stable disease (SD) or better, and the safety profile of nivolumab was considered acceptable.
“Nivolumab offers a favorable treatment outcome for patients who have relapsed disease after autologous stem cell transplant,” said Michelle Fanale, MD, of the University of Texas MD Anderson Cancer Center in Houston.
Dr Fanale presented results from CheckMate-205 at 14-ICML. The study was sponsored by Bristol-Myers Squibb Company.
CheckMate-205 enrolled 243 adults with relapsed or refractory cHL who had undergone auto-HSCT. Patients were divided into 3 cohorts:
- Cohort A included patients who were naïve to BV (n=63)
- Cohort B included patients who received BV only after auto-HSCT (n=80)
- Cohort C included patients who received BV before and/or after auto-HSCT (n=100).
All patients received nivolumab at 3 mg/kg once every 2 weeks until disease progression or unacceptable toxicity.
In cohort C, patients who were in complete response (CR) for 1 year were to discontinue nivolumab, but they could resume treatment with the drug if they relapsed within 2 years.
Patient characteristics
The median age was 33 (range, 18-65) in cohort A, 37 (range, 18-72) in cohort B, and 32 (range, 19-69) in cohort C.
ECOG performance status was 0 for 62% of patients in cohort A, 53% in cohort B, and 50% in cohort C. The remaining patients had a performance status of 1.
The percentage of patients with stage IV disease was 38% in cohort A, 68% in cohort B, and 61% in cohort C.
The median number of prior therapies was 2 (range, 2-8) in cohort A, 4 (range, 3-15) in cohort B, and 4 (range, 2-9) in cohort C. Fifty-nine percent, 74%, and 69% of patients, respectively, had received prior radiotherapy.
The median time from diagnosis to the first dose of nivolumab was 3.1 years (range, 1.0-30.6) in cohort A, 6.2 years (range, 1.3-25.1) in cohort B, and 3.5 years (range, 1.0-24.9) in cohort C.
The median time from auto-HSCT to the first dose of nivolumab was 1.0 years (range, 0.3-18.2) in cohort A, 3.4 years (range, 0.2-19.0) in cohort B, and 1.7 years (range, 0.2-17.0) in cohort C.
Safety
The most common drug-related adverse events (AEs) were fatigue (23% any grade, 1% grade 3/4), diarrhea (15% any grade, 1% grade 3/4), infusion-related reactions (14% any grade, <1% grade 3/4), rash (12% any grade, 1% grade 3/4), nausea (10% grade 1/2), and pruritus (10% grade 1/2).
The most common drug-related serious AEs were infusion-related reactions (2% any grade, <1% grade 3/4) and pneumonitis (1% grade 1/2).
Drug-related AEs leading to treatment discontinuation were pneumonitis (2% grade 1/2) and autoimmune hepatitis (1% grade 3/4).
There were no deaths due to drug-related AEs.
Response
The objective response rate was 69% overall, 65% in cohort A, 68% in cohort B, and 73% in cohort C.
CR was the best response for 16% of all patients, 29% of cohort A, 13% of cohort B, and 12% of cohort C.
Partial response (PR) was the best response for 53% of all patients, 37% of patients in cohort A, 55% in cohort B, and 61% in cohort C.
SD was the best response for 19% of all patients, 24% of patients in cohort A, 21% in cohort B, and 15% in cohort C.
In post-hoc analyses, responses were similar irrespective of BV treatment sequence.
The median duration of response was 17 months overall, 20 months for cohort A, 16 months for cohort B, and 15 months for cohort C.
The median duration of response in patients with a CR was 20 months overall and for cohorts A and B, but it was 15 months for cohort C.
The median duration of response in patients with a PR was 13 months overall, 17 months for cohort A, 11 months for cohort B, and 13 months for cohort C.
Survival
The median PFS for all patients was 15 months (range, 11-19). The median PFS was 22 months (range, 19-not reached) for patients who achieved a CR, 15 months (range, 11-19) for those who achieved a PR, and 11 months (range, 6-18) for those who had SD.
The median PFS was 18 months (range, 11-22) for patients in cohort A, 15 months (range, 11-20) for cohort B, and 12 months (range, 11-18) for cohort C.
The median overall survival (OS) has not been reached in any of the cohorts. The 12-months OS is 92% overall, 93% in cohort A, 95% in cohort B, and 90% in cohort C.
Patient status after extended follow-up
Forty percent of all patients were still on treatment after extended follow-up, as were 48% of patients in cohort A, 40% in cohort B, and 35% in cohort C.
The most common reason for stopping treatment was disease progression—25% of cohort A, 28% of cohort B, and 24% of cohort C.
Patients also stopped treatment due to nivolumab-related toxicity—5% in cohort A, 11% in cohort B, and 7% in cohort C. Three percent, 1%, and 1%, respectively, stopped due to AEs unrelated to nivolumab.
Three percent of patients in cohort C stopped because they had attained the maximum clinical benefit, and 8% in cohort C completed treatment. This includes 7 patients who discontinued treatment because they were in CR for 1 year.
None of the patients in cohort A or B discontinued because they attained the maximum clinical benefit or because they completed treatment.
Eight percent of patients in cohort A, 10% in cohort B, and 17% in cohort C discontinued so they could proceed to HSCT.
Outcomes after allo-HSCT
Forty-four patients received allogeneic (allo-) HSCT after nivolumab. The median post-HSCT follow-up was 5.5 months (range, 0-19), and the median time from last dose of nivolumab to allo-HSCT was 1.6 months (range, 0.5-13.5).
At 100 days, the rate of grade 2-4 acute graft-vs-host disease (GVHD) was 27%. The rate of grade 3-4 acute GVHD was 17%, and the rate of chronic GVHD was 10%. At 6 months, the rates were 30%, 20%, and 15%, respectively.
The incidence of transplant-related mortality was 13% at 100 days and at 6 months.
“While there are risks, potentially, for acute GVHD and transplant-related mortality, these aren’t necessarily significantly different from what we’ve seen from other historical publications,” Dr Fanale said.
She cited data showing that the 100-day incidence of acute GVHD in cHL patients who underwent allo-HSCT ranges from 26% to 60%, and the incidence of transplant-related mortality in these patients ranges from 6% to 28%.
LUGANO, SWITZERLAND—Nivolumab can provide long-term treatment for a broad range of adults who have relapsed or refractory classical Hodgkin lymphoma (cHL) after autologous hematopoietic stem cell transplant (auto-HSCT), according to a presentation at the 14th International Conference on Malignant Lymphoma (ICML).
In the phase 2 CheckMate-205 study, cHL patients achieved durable responses regardless of the depth of response, previous exposure to brentuximab vedotin (BV), and refractoriness to prior therapies.
Researchers observed sustained progression-free survival (PFS) in patients with stable disease (SD) or better, and the safety profile of nivolumab was considered acceptable.
“Nivolumab offers a favorable treatment outcome for patients who have relapsed disease after autologous stem cell transplant,” said Michelle Fanale, MD, of the University of Texas MD Anderson Cancer Center in Houston.
Dr Fanale presented results from CheckMate-205 at 14-ICML. The study was sponsored by Bristol-Myers Squibb Company.
CheckMate-205 enrolled 243 adults with relapsed or refractory cHL who had undergone auto-HSCT. Patients were divided into 3 cohorts:
- Cohort A included patients who were naïve to BV (n=63)
- Cohort B included patients who received BV only after auto-HSCT (n=80)
- Cohort C included patients who received BV before and/or after auto-HSCT (n=100).
All patients received nivolumab at 3 mg/kg once every 2 weeks until disease progression or unacceptable toxicity.
In cohort C, patients who were in complete response (CR) for 1 year were to discontinue nivolumab, but they could resume treatment with the drug if they relapsed within 2 years.
Patient characteristics
The median age was 33 (range, 18-65) in cohort A, 37 (range, 18-72) in cohort B, and 32 (range, 19-69) in cohort C.
ECOG performance status was 0 for 62% of patients in cohort A, 53% in cohort B, and 50% in cohort C. The remaining patients had a performance status of 1.
The percentage of patients with stage IV disease was 38% in cohort A, 68% in cohort B, and 61% in cohort C.
The median number of prior therapies was 2 (range, 2-8) in cohort A, 4 (range, 3-15) in cohort B, and 4 (range, 2-9) in cohort C. Fifty-nine percent, 74%, and 69% of patients, respectively, had received prior radiotherapy.
The median time from diagnosis to the first dose of nivolumab was 3.1 years (range, 1.0-30.6) in cohort A, 6.2 years (range, 1.3-25.1) in cohort B, and 3.5 years (range, 1.0-24.9) in cohort C.
The median time from auto-HSCT to the first dose of nivolumab was 1.0 years (range, 0.3-18.2) in cohort A, 3.4 years (range, 0.2-19.0) in cohort B, and 1.7 years (range, 0.2-17.0) in cohort C.
Safety
The most common drug-related adverse events (AEs) were fatigue (23% any grade, 1% grade 3/4), diarrhea (15% any grade, 1% grade 3/4), infusion-related reactions (14% any grade, <1% grade 3/4), rash (12% any grade, 1% grade 3/4), nausea (10% grade 1/2), and pruritus (10% grade 1/2).
The most common drug-related serious AEs were infusion-related reactions (2% any grade, <1% grade 3/4) and pneumonitis (1% grade 1/2).
Drug-related AEs leading to treatment discontinuation were pneumonitis (2% grade 1/2) and autoimmune hepatitis (1% grade 3/4).
There were no deaths due to drug-related AEs.
Response
The objective response rate was 69% overall, 65% in cohort A, 68% in cohort B, and 73% in cohort C.
CR was the best response for 16% of all patients, 29% of cohort A, 13% of cohort B, and 12% of cohort C.
Partial response (PR) was the best response for 53% of all patients, 37% of patients in cohort A, 55% in cohort B, and 61% in cohort C.
SD was the best response for 19% of all patients, 24% of patients in cohort A, 21% in cohort B, and 15% in cohort C.
In post-hoc analyses, responses were similar irrespective of BV treatment sequence.
The median duration of response was 17 months overall, 20 months for cohort A, 16 months for cohort B, and 15 months for cohort C.
The median duration of response in patients with a CR was 20 months overall and for cohorts A and B, but it was 15 months for cohort C.
The median duration of response in patients with a PR was 13 months overall, 17 months for cohort A, 11 months for cohort B, and 13 months for cohort C.
Survival
The median PFS for all patients was 15 months (range, 11-19). The median PFS was 22 months (range, 19-not reached) for patients who achieved a CR, 15 months (range, 11-19) for those who achieved a PR, and 11 months (range, 6-18) for those who had SD.
The median PFS was 18 months (range, 11-22) for patients in cohort A, 15 months (range, 11-20) for cohort B, and 12 months (range, 11-18) for cohort C.
The median overall survival (OS) has not been reached in any of the cohorts. The 12-months OS is 92% overall, 93% in cohort A, 95% in cohort B, and 90% in cohort C.
Patient status after extended follow-up
Forty percent of all patients were still on treatment after extended follow-up, as were 48% of patients in cohort A, 40% in cohort B, and 35% in cohort C.
The most common reason for stopping treatment was disease progression—25% of cohort A, 28% of cohort B, and 24% of cohort C.
Patients also stopped treatment due to nivolumab-related toxicity—5% in cohort A, 11% in cohort B, and 7% in cohort C. Three percent, 1%, and 1%, respectively, stopped due to AEs unrelated to nivolumab.
Three percent of patients in cohort C stopped because they had attained the maximum clinical benefit, and 8% in cohort C completed treatment. This includes 7 patients who discontinued treatment because they were in CR for 1 year.
None of the patients in cohort A or B discontinued because they attained the maximum clinical benefit or because they completed treatment.
Eight percent of patients in cohort A, 10% in cohort B, and 17% in cohort C discontinued so they could proceed to HSCT.
Outcomes after allo-HSCT
Forty-four patients received allogeneic (allo-) HSCT after nivolumab. The median post-HSCT follow-up was 5.5 months (range, 0-19), and the median time from last dose of nivolumab to allo-HSCT was 1.6 months (range, 0.5-13.5).
At 100 days, the rate of grade 2-4 acute graft-vs-host disease (GVHD) was 27%. The rate of grade 3-4 acute GVHD was 17%, and the rate of chronic GVHD was 10%. At 6 months, the rates were 30%, 20%, and 15%, respectively.
The incidence of transplant-related mortality was 13% at 100 days and at 6 months.
“While there are risks, potentially, for acute GVHD and transplant-related mortality, these aren’t necessarily significantly different from what we’ve seen from other historical publications,” Dr Fanale said.
She cited data showing that the 100-day incidence of acute GVHD in cHL patients who underwent allo-HSCT ranges from 26% to 60%, and the incidence of transplant-related mortality in these patients ranges from 6% to 28%.
LUGANO, SWITZERLAND—Nivolumab can provide long-term treatment for a broad range of adults who have relapsed or refractory classical Hodgkin lymphoma (cHL) after autologous hematopoietic stem cell transplant (auto-HSCT), according to a presentation at the 14th International Conference on Malignant Lymphoma (ICML).
In the phase 2 CheckMate-205 study, cHL patients achieved durable responses regardless of the depth of response, previous exposure to brentuximab vedotin (BV), and refractoriness to prior therapies.
Researchers observed sustained progression-free survival (PFS) in patients with stable disease (SD) or better, and the safety profile of nivolumab was considered acceptable.
“Nivolumab offers a favorable treatment outcome for patients who have relapsed disease after autologous stem cell transplant,” said Michelle Fanale, MD, of the University of Texas MD Anderson Cancer Center in Houston.
Dr Fanale presented results from CheckMate-205 at 14-ICML. The study was sponsored by Bristol-Myers Squibb Company.
CheckMate-205 enrolled 243 adults with relapsed or refractory cHL who had undergone auto-HSCT. Patients were divided into 3 cohorts:
- Cohort A included patients who were naïve to BV (n=63)
- Cohort B included patients who received BV only after auto-HSCT (n=80)
- Cohort C included patients who received BV before and/or after auto-HSCT (n=100).
All patients received nivolumab at 3 mg/kg once every 2 weeks until disease progression or unacceptable toxicity.
In cohort C, patients who were in complete response (CR) for 1 year were to discontinue nivolumab, but they could resume treatment with the drug if they relapsed within 2 years.
Patient characteristics
The median age was 33 (range, 18-65) in cohort A, 37 (range, 18-72) in cohort B, and 32 (range, 19-69) in cohort C.
ECOG performance status was 0 for 62% of patients in cohort A, 53% in cohort B, and 50% in cohort C. The remaining patients had a performance status of 1.
The percentage of patients with stage IV disease was 38% in cohort A, 68% in cohort B, and 61% in cohort C.
The median number of prior therapies was 2 (range, 2-8) in cohort A, 4 (range, 3-15) in cohort B, and 4 (range, 2-9) in cohort C. Fifty-nine percent, 74%, and 69% of patients, respectively, had received prior radiotherapy.
The median time from diagnosis to the first dose of nivolumab was 3.1 years (range, 1.0-30.6) in cohort A, 6.2 years (range, 1.3-25.1) in cohort B, and 3.5 years (range, 1.0-24.9) in cohort C.
The median time from auto-HSCT to the first dose of nivolumab was 1.0 years (range, 0.3-18.2) in cohort A, 3.4 years (range, 0.2-19.0) in cohort B, and 1.7 years (range, 0.2-17.0) in cohort C.
Safety
The most common drug-related adverse events (AEs) were fatigue (23% any grade, 1% grade 3/4), diarrhea (15% any grade, 1% grade 3/4), infusion-related reactions (14% any grade, <1% grade 3/4), rash (12% any grade, 1% grade 3/4), nausea (10% grade 1/2), and pruritus (10% grade 1/2).
The most common drug-related serious AEs were infusion-related reactions (2% any grade, <1% grade 3/4) and pneumonitis (1% grade 1/2).
Drug-related AEs leading to treatment discontinuation were pneumonitis (2% grade 1/2) and autoimmune hepatitis (1% grade 3/4).
There were no deaths due to drug-related AEs.
Response
The objective response rate was 69% overall, 65% in cohort A, 68% in cohort B, and 73% in cohort C.
CR was the best response for 16% of all patients, 29% of cohort A, 13% of cohort B, and 12% of cohort C.
Partial response (PR) was the best response for 53% of all patients, 37% of patients in cohort A, 55% in cohort B, and 61% in cohort C.
SD was the best response for 19% of all patients, 24% of patients in cohort A, 21% in cohort B, and 15% in cohort C.
In post-hoc analyses, responses were similar irrespective of BV treatment sequence.
The median duration of response was 17 months overall, 20 months for cohort A, 16 months for cohort B, and 15 months for cohort C.
The median duration of response in patients with a CR was 20 months overall and for cohorts A and B, but it was 15 months for cohort C.
The median duration of response in patients with a PR was 13 months overall, 17 months for cohort A, 11 months for cohort B, and 13 months for cohort C.
Survival
The median PFS for all patients was 15 months (range, 11-19). The median PFS was 22 months (range, 19-not reached) for patients who achieved a CR, 15 months (range, 11-19) for those who achieved a PR, and 11 months (range, 6-18) for those who had SD.
The median PFS was 18 months (range, 11-22) for patients in cohort A, 15 months (range, 11-20) for cohort B, and 12 months (range, 11-18) for cohort C.
The median overall survival (OS) has not been reached in any of the cohorts. The 12-months OS is 92% overall, 93% in cohort A, 95% in cohort B, and 90% in cohort C.
Patient status after extended follow-up
Forty percent of all patients were still on treatment after extended follow-up, as were 48% of patients in cohort A, 40% in cohort B, and 35% in cohort C.
The most common reason for stopping treatment was disease progression—25% of cohort A, 28% of cohort B, and 24% of cohort C.
Patients also stopped treatment due to nivolumab-related toxicity—5% in cohort A, 11% in cohort B, and 7% in cohort C. Three percent, 1%, and 1%, respectively, stopped due to AEs unrelated to nivolumab.
Three percent of patients in cohort C stopped because they had attained the maximum clinical benefit, and 8% in cohort C completed treatment. This includes 7 patients who discontinued treatment because they were in CR for 1 year.
None of the patients in cohort A or B discontinued because they attained the maximum clinical benefit or because they completed treatment.
Eight percent of patients in cohort A, 10% in cohort B, and 17% in cohort C discontinued so they could proceed to HSCT.
Outcomes after allo-HSCT
Forty-four patients received allogeneic (allo-) HSCT after nivolumab. The median post-HSCT follow-up was 5.5 months (range, 0-19), and the median time from last dose of nivolumab to allo-HSCT was 1.6 months (range, 0.5-13.5).
At 100 days, the rate of grade 2-4 acute graft-vs-host disease (GVHD) was 27%. The rate of grade 3-4 acute GVHD was 17%, and the rate of chronic GVHD was 10%. At 6 months, the rates were 30%, 20%, and 15%, respectively.
The incidence of transplant-related mortality was 13% at 100 days and at 6 months.
“While there are risks, potentially, for acute GVHD and transplant-related mortality, these aren’t necessarily significantly different from what we’ve seen from other historical publications,” Dr Fanale said.
She cited data showing that the 100-day incidence of acute GVHD in cHL patients who underwent allo-HSCT ranges from 26% to 60%, and the incidence of transplant-related mortality in these patients ranges from 6% to 28%.
Countries with high malaria burden don’t receive research funding
A new study has revealed inequalities in malaria research funding in sub-Saharan Africa.
The study showed that some countries with a high malaria burden—such as Sierra Leone, Congo, Central African Republic, and Guinea—received little to no funding for malaria research in recent years.
However, other countries—such as Tanzania, Uganda, and Kenya—received close to $100 million in funding for malaria research.
Michael Head, PhD, of the University of Southampton in the UK, and his colleagues reported these findings in The Lancet Global Health.
“We have been able to provide a comprehensive overview of the landscape of funding for malaria in sub-Saharan Africa, a massive area where around 90% of worldwide malaria cases occur,” Dr Head said.
“We’ve shown that there are countries that are being neglected, and the global health community should reconsider strategies around resource allocation to reduce inequities and improve equality.”
For this study, Dr Head and his colleagues analyzed funding data spanning the period from 1997 to 2013. The data were sourced from 13 major public and philanthropic global health funders, as well as from funding databases.
The researchers ranked 45 countries according to the level of malaria research funding they received.
All of the countries studied received funding for malaria control, which includes investment for bed nets, public health schemes, and antimalarial drugs.
However, 8 of the 45 countries did not receive any funding related to malaria research. This included Central African Republic, Sierra Leone, and Congo—countries with a “reasonably high” malaria burden/mortality rate, according to Dr Head and his colleagues.
In all, there were 333 research awards, totaling $814.4 million. The countries that received the most research funding were Tanzania ($107.8 million), Uganda ($97.9 million), and Kenya ($92.9 million).
The 8 countries that received no research funding were Cape Verde, Botswana, Djibouti, Central African Republic, Mauritania, Congo, Chad, and Sierra Leone.
Dr Head and his colleagues suggested that the reason for the disparity in funding allocation could be, in part, due to the presence of established high-quality research infrastructure in countries such as Tanzania and Kenya, and political instability and poor healthcare infrastructures in lower-ranked nations such as Central African Republic or Sierra Leone.
“[N]ew investment in malaria research and development in these areas can encourage the development of improved health systems,” Dr Head said. “Many countries in sub-Saharan Africa simply do not have an established research infrastructure, and it is difficult for research funders to make investments in these settings.”
“Ultimately, however, there are neglected populations in these countries who suffer greatly from malaria and other diseases. Investments in health improve the wealth of a nation, and we need to be smarter with allocating limited resources to best help to reduce clear health inequalities.”
A new study has revealed inequalities in malaria research funding in sub-Saharan Africa.
The study showed that some countries with a high malaria burden—such as Sierra Leone, Congo, Central African Republic, and Guinea—received little to no funding for malaria research in recent years.
However, other countries—such as Tanzania, Uganda, and Kenya—received close to $100 million in funding for malaria research.
Michael Head, PhD, of the University of Southampton in the UK, and his colleagues reported these findings in The Lancet Global Health.
“We have been able to provide a comprehensive overview of the landscape of funding for malaria in sub-Saharan Africa, a massive area where around 90% of worldwide malaria cases occur,” Dr Head said.
“We’ve shown that there are countries that are being neglected, and the global health community should reconsider strategies around resource allocation to reduce inequities and improve equality.”
For this study, Dr Head and his colleagues analyzed funding data spanning the period from 1997 to 2013. The data were sourced from 13 major public and philanthropic global health funders, as well as from funding databases.
The researchers ranked 45 countries according to the level of malaria research funding they received.
All of the countries studied received funding for malaria control, which includes investment for bed nets, public health schemes, and antimalarial drugs.
However, 8 of the 45 countries did not receive any funding related to malaria research. This included Central African Republic, Sierra Leone, and Congo—countries with a “reasonably high” malaria burden/mortality rate, according to Dr Head and his colleagues.
In all, there were 333 research awards, totaling $814.4 million. The countries that received the most research funding were Tanzania ($107.8 million), Uganda ($97.9 million), and Kenya ($92.9 million).
The 8 countries that received no research funding were Cape Verde, Botswana, Djibouti, Central African Republic, Mauritania, Congo, Chad, and Sierra Leone.
Dr Head and his colleagues suggested that the reason for the disparity in funding allocation could be, in part, due to the presence of established high-quality research infrastructure in countries such as Tanzania and Kenya, and political instability and poor healthcare infrastructures in lower-ranked nations such as Central African Republic or Sierra Leone.
“[N]ew investment in malaria research and development in these areas can encourage the development of improved health systems,” Dr Head said. “Many countries in sub-Saharan Africa simply do not have an established research infrastructure, and it is difficult for research funders to make investments in these settings.”
“Ultimately, however, there are neglected populations in these countries who suffer greatly from malaria and other diseases. Investments in health improve the wealth of a nation, and we need to be smarter with allocating limited resources to best help to reduce clear health inequalities.”
A new study has revealed inequalities in malaria research funding in sub-Saharan Africa.
The study showed that some countries with a high malaria burden—such as Sierra Leone, Congo, Central African Republic, and Guinea—received little to no funding for malaria research in recent years.
However, other countries—such as Tanzania, Uganda, and Kenya—received close to $100 million in funding for malaria research.
Michael Head, PhD, of the University of Southampton in the UK, and his colleagues reported these findings in The Lancet Global Health.
“We have been able to provide a comprehensive overview of the landscape of funding for malaria in sub-Saharan Africa, a massive area where around 90% of worldwide malaria cases occur,” Dr Head said.
“We’ve shown that there are countries that are being neglected, and the global health community should reconsider strategies around resource allocation to reduce inequities and improve equality.”
For this study, Dr Head and his colleagues analyzed funding data spanning the period from 1997 to 2013. The data were sourced from 13 major public and philanthropic global health funders, as well as from funding databases.
The researchers ranked 45 countries according to the level of malaria research funding they received.
All of the countries studied received funding for malaria control, which includes investment for bed nets, public health schemes, and antimalarial drugs.
However, 8 of the 45 countries did not receive any funding related to malaria research. This included Central African Republic, Sierra Leone, and Congo—countries with a “reasonably high” malaria burden/mortality rate, according to Dr Head and his colleagues.
In all, there were 333 research awards, totaling $814.4 million. The countries that received the most research funding were Tanzania ($107.8 million), Uganda ($97.9 million), and Kenya ($92.9 million).
The 8 countries that received no research funding were Cape Verde, Botswana, Djibouti, Central African Republic, Mauritania, Congo, Chad, and Sierra Leone.
Dr Head and his colleagues suggested that the reason for the disparity in funding allocation could be, in part, due to the presence of established high-quality research infrastructure in countries such as Tanzania and Kenya, and political instability and poor healthcare infrastructures in lower-ranked nations such as Central African Republic or Sierra Leone.
“[N]ew investment in malaria research and development in these areas can encourage the development of improved health systems,” Dr Head said. “Many countries in sub-Saharan Africa simply do not have an established research infrastructure, and it is difficult for research funders to make investments in these settings.”
“Ultimately, however, there are neglected populations in these countries who suffer greatly from malaria and other diseases. Investments in health improve the wealth of a nation, and we need to be smarter with allocating limited resources to best help to reduce clear health inequalities.”
Oral combo produces deep, durable responses in MM
An all-oral treatment regimen can produce deep and durable responses in patients with newly diagnosed multiple myeloma (MM), according to a speaker at the 22nd Congress of the European Hematology Association (EHA).
In a phase 1/2 study, patients with newly diagnosed MM received treatment with ixazomib, lenalidomide, and dexamethasone for up to 12 cycles, followed by maintenance with ixazomib alone.
The overall response rate was 88% for the entire cohort and 80% among patients who did not proceed to transplant.
The median progression-free survival was 35.4 months in the entire cohort and 29.4 months in patients who did not proceed to transplant.
Most patients did not complete all 12 cycles of induction, but 38% proceeded to maintenance, and 12% remain on study treatment at a median follow-up of 56 months.
Shaji Kumar, MD, of the Mayo Clinic in Rochester, Minnesota, presented these results at the EHA Congress as abstract S408. The research was sponsored by Millennium Pharmaceuticals, Inc., a subsidiary of Takeda Pharmaceutical Company Limited.
Patients
The trial included 65 patients. Their median age was 66 (range, 34-86), and 55% were male. Eight percent of patients had high-risk cytogenetics.
ECOG performance status was 0 for 43% of patients, 1 for 52%, and 2 for 5%. ISS stage was 1 for 43% of patients, 2 for 43%, and 3 for 14%.
Treatment
Patients received ixazomib (1.68 - 3.95 mg/m2 in phase 1 and 4.0 mg in phase 2 on days 1, 8, and 15) plus lenalidomide (25 mg on days 1-21), and dexamethasone (40 mg on days 1, 8, 15, and 22) for up to twelve, 28-day cycles. Patients could then receive ixazomib maintenance until disease progression or unacceptable toxicity.
Twenty-three patients (35%) discontinued induction to undergo hematopoietic stem cell transplant (HSCT).
Thirty-seven patients discontinued study treatment for other reasons—17 of them during induction. Twenty-one patients discontinued due to progressive disease, 9 due to adverse events (AEs), 5 due to patient withdrawal, 1 due to unsatisfactory response, and 1 due to other reasons.
Twenty-five patients completed induction and went on to receive ixazomib maintenance. Five patients remain on study treatment.
Safety
Seventy-eight percent of patients had a grade 3 or higher AE, 46% had a serious AE, 57% had an AE leading to dose reduction, and 15% had an AE leading to discontinuation of any of the study drugs. There were 2 on-study deaths.
The most common grade 3 or higher AEs were neutropenia, thrombocytopenia, diarrhea, back pain, vomiting, nausea, peripheral neuropathy, and rashes/eruptions/exanthems.
Efficacy
The overall response rate was 88% for the entire cohort and 80% among patients who did not go on to receive HSCT.
The complete response (CR) rates were 23% and 32%, respectively. Thirty four percent and 32%, respectively, had a very good partial response (VGPR). And 30% and 17%, respectively, had a partial response (PR).
Thirty-two percent of patients who received maintenance (n=8) had an improvement in their response during the maintenance phase. Two patients went from a VGPR to a stringent CR, 3 went from a VGPR to a CR, 2 went from a VGPR to a near CR, and 1 went from a PR to a VGPR.
Sixteen patients were evaluated for minimal residual disease (MRD). Of the patients with a stringent CR/CR, 89% (8/9) were MRD-negative.
The median progression-free survival was 35.4 months in the entire cohort and 29.4 months in patients who did not proceed to HSCT. The 4-year overall survival rate was 84% and 82%, respectively.
“Long-term follow-up, a median follow-up of 56 months, with the combination of ixazomib, lenalidomide, and dexamethasone demonstrates that this is an efficacious regimen for newly diagnosed myeloma patients, with excellent tolerability, and something that can be maintained for a long period of time,” Dr Kumar said. “These results form the basis for an ongoing phase 3 program.”
An all-oral treatment regimen can produce deep and durable responses in patients with newly diagnosed multiple myeloma (MM), according to a speaker at the 22nd Congress of the European Hematology Association (EHA).
In a phase 1/2 study, patients with newly diagnosed MM received treatment with ixazomib, lenalidomide, and dexamethasone for up to 12 cycles, followed by maintenance with ixazomib alone.
The overall response rate was 88% for the entire cohort and 80% among patients who did not proceed to transplant.
The median progression-free survival was 35.4 months in the entire cohort and 29.4 months in patients who did not proceed to transplant.
Most patients did not complete all 12 cycles of induction, but 38% proceeded to maintenance, and 12% remain on study treatment at a median follow-up of 56 months.
Shaji Kumar, MD, of the Mayo Clinic in Rochester, Minnesota, presented these results at the EHA Congress as abstract S408. The research was sponsored by Millennium Pharmaceuticals, Inc., a subsidiary of Takeda Pharmaceutical Company Limited.
Patients
The trial included 65 patients. Their median age was 66 (range, 34-86), and 55% were male. Eight percent of patients had high-risk cytogenetics.
ECOG performance status was 0 for 43% of patients, 1 for 52%, and 2 for 5%. ISS stage was 1 for 43% of patients, 2 for 43%, and 3 for 14%.
Treatment
Patients received ixazomib (1.68 - 3.95 mg/m2 in phase 1 and 4.0 mg in phase 2 on days 1, 8, and 15) plus lenalidomide (25 mg on days 1-21), and dexamethasone (40 mg on days 1, 8, 15, and 22) for up to twelve, 28-day cycles. Patients could then receive ixazomib maintenance until disease progression or unacceptable toxicity.
Twenty-three patients (35%) discontinued induction to undergo hematopoietic stem cell transplant (HSCT).
Thirty-seven patients discontinued study treatment for other reasons—17 of them during induction. Twenty-one patients discontinued due to progressive disease, 9 due to adverse events (AEs), 5 due to patient withdrawal, 1 due to unsatisfactory response, and 1 due to other reasons.
Twenty-five patients completed induction and went on to receive ixazomib maintenance. Five patients remain on study treatment.
Safety
Seventy-eight percent of patients had a grade 3 or higher AE, 46% had a serious AE, 57% had an AE leading to dose reduction, and 15% had an AE leading to discontinuation of any of the study drugs. There were 2 on-study deaths.
The most common grade 3 or higher AEs were neutropenia, thrombocytopenia, diarrhea, back pain, vomiting, nausea, peripheral neuropathy, and rashes/eruptions/exanthems.
Efficacy
The overall response rate was 88% for the entire cohort and 80% among patients who did not go on to receive HSCT.
The complete response (CR) rates were 23% and 32%, respectively. Thirty four percent and 32%, respectively, had a very good partial response (VGPR). And 30% and 17%, respectively, had a partial response (PR).
Thirty-two percent of patients who received maintenance (n=8) had an improvement in their response during the maintenance phase. Two patients went from a VGPR to a stringent CR, 3 went from a VGPR to a CR, 2 went from a VGPR to a near CR, and 1 went from a PR to a VGPR.
Sixteen patients were evaluated for minimal residual disease (MRD). Of the patients with a stringent CR/CR, 89% (8/9) were MRD-negative.
The median progression-free survival was 35.4 months in the entire cohort and 29.4 months in patients who did not proceed to HSCT. The 4-year overall survival rate was 84% and 82%, respectively.
“Long-term follow-up, a median follow-up of 56 months, with the combination of ixazomib, lenalidomide, and dexamethasone demonstrates that this is an efficacious regimen for newly diagnosed myeloma patients, with excellent tolerability, and something that can be maintained for a long period of time,” Dr Kumar said. “These results form the basis for an ongoing phase 3 program.”
An all-oral treatment regimen can produce deep and durable responses in patients with newly diagnosed multiple myeloma (MM), according to a speaker at the 22nd Congress of the European Hematology Association (EHA).
In a phase 1/2 study, patients with newly diagnosed MM received treatment with ixazomib, lenalidomide, and dexamethasone for up to 12 cycles, followed by maintenance with ixazomib alone.
The overall response rate was 88% for the entire cohort and 80% among patients who did not proceed to transplant.
The median progression-free survival was 35.4 months in the entire cohort and 29.4 months in patients who did not proceed to transplant.
Most patients did not complete all 12 cycles of induction, but 38% proceeded to maintenance, and 12% remain on study treatment at a median follow-up of 56 months.
Shaji Kumar, MD, of the Mayo Clinic in Rochester, Minnesota, presented these results at the EHA Congress as abstract S408. The research was sponsored by Millennium Pharmaceuticals, Inc., a subsidiary of Takeda Pharmaceutical Company Limited.
Patients
The trial included 65 patients. Their median age was 66 (range, 34-86), and 55% were male. Eight percent of patients had high-risk cytogenetics.
ECOG performance status was 0 for 43% of patients, 1 for 52%, and 2 for 5%. ISS stage was 1 for 43% of patients, 2 for 43%, and 3 for 14%.
Treatment
Patients received ixazomib (1.68 - 3.95 mg/m2 in phase 1 and 4.0 mg in phase 2 on days 1, 8, and 15) plus lenalidomide (25 mg on days 1-21), and dexamethasone (40 mg on days 1, 8, 15, and 22) for up to twelve, 28-day cycles. Patients could then receive ixazomib maintenance until disease progression or unacceptable toxicity.
Twenty-three patients (35%) discontinued induction to undergo hematopoietic stem cell transplant (HSCT).
Thirty-seven patients discontinued study treatment for other reasons—17 of them during induction. Twenty-one patients discontinued due to progressive disease, 9 due to adverse events (AEs), 5 due to patient withdrawal, 1 due to unsatisfactory response, and 1 due to other reasons.
Twenty-five patients completed induction and went on to receive ixazomib maintenance. Five patients remain on study treatment.
Safety
Seventy-eight percent of patients had a grade 3 or higher AE, 46% had a serious AE, 57% had an AE leading to dose reduction, and 15% had an AE leading to discontinuation of any of the study drugs. There were 2 on-study deaths.
The most common grade 3 or higher AEs were neutropenia, thrombocytopenia, diarrhea, back pain, vomiting, nausea, peripheral neuropathy, and rashes/eruptions/exanthems.
Efficacy
The overall response rate was 88% for the entire cohort and 80% among patients who did not go on to receive HSCT.
The complete response (CR) rates were 23% and 32%, respectively. Thirty four percent and 32%, respectively, had a very good partial response (VGPR). And 30% and 17%, respectively, had a partial response (PR).
Thirty-two percent of patients who received maintenance (n=8) had an improvement in their response during the maintenance phase. Two patients went from a VGPR to a stringent CR, 3 went from a VGPR to a CR, 2 went from a VGPR to a near CR, and 1 went from a PR to a VGPR.
Sixteen patients were evaluated for minimal residual disease (MRD). Of the patients with a stringent CR/CR, 89% (8/9) were MRD-negative.
The median progression-free survival was 35.4 months in the entire cohort and 29.4 months in patients who did not proceed to HSCT. The 4-year overall survival rate was 84% and 82%, respectively.
“Long-term follow-up, a median follow-up of 56 months, with the combination of ixazomib, lenalidomide, and dexamethasone demonstrates that this is an efficacious regimen for newly diagnosed myeloma patients, with excellent tolerability, and something that can be maintained for a long period of time,” Dr Kumar said. “These results form the basis for an ongoing phase 3 program.”
Mapping the genomic landscape of T-ALL
Researchers say they have uncovered new details of the genomic landscape of T-lineage acute lymphoblastic leukemia (T-ALL).
The team believes their findings will aid the development of drugs to target newly discovered mutations and enable researchers to engineer better mouse models to probe the leukemia’s aberrant biological machinery.
Charles Mullighan, MD, MBBS, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues conducted this research and reported their findings in Nature Genetics.
“This first comprehensive and systematic analysis in a large group of patients revealed many new mutations that are biologically significant as well as new drug targets that could be clinically important,” Dr Mullighan said.
“Leukemias typically arise from multiple genetic changes that work together. Most previous studies have not had the breadth of genomic data in enough patients to identify the constellations of mutations and recognize their associations.”
Dr Mullighan and his colleagues sequenced the genomes of 264 children and young adults with T-ALL. This revealed 106 driver genes, half of which had not been identified in childhood T-ALL.
“We went into this study knowing that we didn’t know the full genomic landscape of T-ALL,” said Stephen Hunger, MD, of the Children’s Hospital of Philadelphia in Pennsylvania.
“But we were surprised that over half of the new targets and mutations were previously unrecognized. It was particularly unexpected and very striking that some mutations were exclusively found in some subtypes of T-ALL but not others.”
The researchers’ analysis confirmed that T-ALL was driven by mutations in known signaling pathways, including JAK-STAT, Ras, and PTEN-PI3K. However, the study also revealed new mutations in those known pathways.
In addition, the researchers identified cases in which the same T-ALL subtype had mutations in different pathways triggered by the same founding mutation.
“We believe this finding suggests we can target such subtypes with an inhibitor drug for one of the pathways, and it’s likely to be effective,” Dr Mullighan said.
He and his colleagues also believe the mutations uncovered in this study will enable researchers to create mouse models that more accurately reflect human T-ALL.
“We now have a launching pad, if you will, to design mouse models that include multiple genetic mutations to more faithfully reflect the leukemias we see in humans,” Dr Mullighan said.
Data from this study are available to researchers through the St. Jude PeCan data portal and the TARGET Data Matrix.
Researchers say they have uncovered new details of the genomic landscape of T-lineage acute lymphoblastic leukemia (T-ALL).
The team believes their findings will aid the development of drugs to target newly discovered mutations and enable researchers to engineer better mouse models to probe the leukemia’s aberrant biological machinery.
Charles Mullighan, MD, MBBS, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues conducted this research and reported their findings in Nature Genetics.
“This first comprehensive and systematic analysis in a large group of patients revealed many new mutations that are biologically significant as well as new drug targets that could be clinically important,” Dr Mullighan said.
“Leukemias typically arise from multiple genetic changes that work together. Most previous studies have not had the breadth of genomic data in enough patients to identify the constellations of mutations and recognize their associations.”
Dr Mullighan and his colleagues sequenced the genomes of 264 children and young adults with T-ALL. This revealed 106 driver genes, half of which had not been identified in childhood T-ALL.
“We went into this study knowing that we didn’t know the full genomic landscape of T-ALL,” said Stephen Hunger, MD, of the Children’s Hospital of Philadelphia in Pennsylvania.
“But we were surprised that over half of the new targets and mutations were previously unrecognized. It was particularly unexpected and very striking that some mutations were exclusively found in some subtypes of T-ALL but not others.”
The researchers’ analysis confirmed that T-ALL was driven by mutations in known signaling pathways, including JAK-STAT, Ras, and PTEN-PI3K. However, the study also revealed new mutations in those known pathways.
In addition, the researchers identified cases in which the same T-ALL subtype had mutations in different pathways triggered by the same founding mutation.
“We believe this finding suggests we can target such subtypes with an inhibitor drug for one of the pathways, and it’s likely to be effective,” Dr Mullighan said.
He and his colleagues also believe the mutations uncovered in this study will enable researchers to create mouse models that more accurately reflect human T-ALL.
“We now have a launching pad, if you will, to design mouse models that include multiple genetic mutations to more faithfully reflect the leukemias we see in humans,” Dr Mullighan said.
Data from this study are available to researchers through the St. Jude PeCan data portal and the TARGET Data Matrix.
Researchers say they have uncovered new details of the genomic landscape of T-lineage acute lymphoblastic leukemia (T-ALL).
The team believes their findings will aid the development of drugs to target newly discovered mutations and enable researchers to engineer better mouse models to probe the leukemia’s aberrant biological machinery.
Charles Mullighan, MD, MBBS, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues conducted this research and reported their findings in Nature Genetics.
“This first comprehensive and systematic analysis in a large group of patients revealed many new mutations that are biologically significant as well as new drug targets that could be clinically important,” Dr Mullighan said.
“Leukemias typically arise from multiple genetic changes that work together. Most previous studies have not had the breadth of genomic data in enough patients to identify the constellations of mutations and recognize their associations.”
Dr Mullighan and his colleagues sequenced the genomes of 264 children and young adults with T-ALL. This revealed 106 driver genes, half of which had not been identified in childhood T-ALL.
“We went into this study knowing that we didn’t know the full genomic landscape of T-ALL,” said Stephen Hunger, MD, of the Children’s Hospital of Philadelphia in Pennsylvania.
“But we were surprised that over half of the new targets and mutations were previously unrecognized. It was particularly unexpected and very striking that some mutations were exclusively found in some subtypes of T-ALL but not others.”
The researchers’ analysis confirmed that T-ALL was driven by mutations in known signaling pathways, including JAK-STAT, Ras, and PTEN-PI3K. However, the study also revealed new mutations in those known pathways.
In addition, the researchers identified cases in which the same T-ALL subtype had mutations in different pathways triggered by the same founding mutation.
“We believe this finding suggests we can target such subtypes with an inhibitor drug for one of the pathways, and it’s likely to be effective,” Dr Mullighan said.
He and his colleagues also believe the mutations uncovered in this study will enable researchers to create mouse models that more accurately reflect human T-ALL.
“We now have a launching pad, if you will, to design mouse models that include multiple genetic mutations to more faithfully reflect the leukemias we see in humans,” Dr Mullighan said.
Data from this study are available to researchers through the St. Jude PeCan data portal and the TARGET Data Matrix.
FDA puts pembrolizumab trials on clinical hold
The US Food and Drug Administration (FDA) has placed clinical holds on 3 trials testing combination therapy with pembrolizumab (Keytruda) in patients with multiple myeloma (MM)—KEYNOTE-183, KEYNOTE-185, and KEYNOTE-023.
In 2 of these trials—KEYNOTE-183 and -185—there were more deaths among patients receiving pembrolizumab than among patients receiving comparator treatments.
KEYNOTE-183 is a phase 3 study of pomalidomide and low-dose dexamethasone with or without pembrolizumab in refractory or relapsed and refractory MM.
KEYNOTE-185 is a phase 3 study of lenalidomide and low-dose dexamethasone with or without pembrolizumab in newly diagnosed and treatment-naïve MM.
The excess deaths in the pembrolizumab arms of KEYNOTE-183 and -185 led to a pause in enrollment for both trials, which was announced last month.
Now, the FDA says available data suggest the risks of pembrolizumab plus pomalidomide or lenalidomide outweigh any potential benefit for MM patients.
Therefore, all patients enrolled in KEYNOTE-183 and -185 will discontinue investigational treatment with pembrolizumab.
The same applies to patients in the pembrolizumab/lenalidomide/dexamethasone cohort of KEYNOTE-023.
KEYNOTE-023 is a phase 1 trial of pembrolizumab in combination with backbone treatments. Cohort 1 of this trial was designed to evaluate pembrolizumab in combination with lenalidomide and dexamethasone in MM patients who received prior treatment with an immunomodulatory agent (lenalidomide, pomalidomide, or thalidomide).
Pembrolizumab is a humanized monoclonal antibody that blocks interaction between the programmed cell death protein 1 (PD-1) and its receptor ligands, PD-L1 and PD-L2.
Pembrolizumab is FDA-approved to treat classical Hodgkin lymphoma, melanoma, non-small cell lung cancer, head and neck cancer, urothelial carcinoma, and microsatellite instability-high solid tumors.
The US Food and Drug Administration (FDA) has placed clinical holds on 3 trials testing combination therapy with pembrolizumab (Keytruda) in patients with multiple myeloma (MM)—KEYNOTE-183, KEYNOTE-185, and KEYNOTE-023.
In 2 of these trials—KEYNOTE-183 and -185—there were more deaths among patients receiving pembrolizumab than among patients receiving comparator treatments.
KEYNOTE-183 is a phase 3 study of pomalidomide and low-dose dexamethasone with or without pembrolizumab in refractory or relapsed and refractory MM.
KEYNOTE-185 is a phase 3 study of lenalidomide and low-dose dexamethasone with or without pembrolizumab in newly diagnosed and treatment-naïve MM.
The excess deaths in the pembrolizumab arms of KEYNOTE-183 and -185 led to a pause in enrollment for both trials, which was announced last month.
Now, the FDA says available data suggest the risks of pembrolizumab plus pomalidomide or lenalidomide outweigh any potential benefit for MM patients.
Therefore, all patients enrolled in KEYNOTE-183 and -185 will discontinue investigational treatment with pembrolizumab.
The same applies to patients in the pembrolizumab/lenalidomide/dexamethasone cohort of KEYNOTE-023.
KEYNOTE-023 is a phase 1 trial of pembrolizumab in combination with backbone treatments. Cohort 1 of this trial was designed to evaluate pembrolizumab in combination with lenalidomide and dexamethasone in MM patients who received prior treatment with an immunomodulatory agent (lenalidomide, pomalidomide, or thalidomide).
Pembrolizumab is a humanized monoclonal antibody that blocks interaction between the programmed cell death protein 1 (PD-1) and its receptor ligands, PD-L1 and PD-L2.
Pembrolizumab is FDA-approved to treat classical Hodgkin lymphoma, melanoma, non-small cell lung cancer, head and neck cancer, urothelial carcinoma, and microsatellite instability-high solid tumors.
The US Food and Drug Administration (FDA) has placed clinical holds on 3 trials testing combination therapy with pembrolizumab (Keytruda) in patients with multiple myeloma (MM)—KEYNOTE-183, KEYNOTE-185, and KEYNOTE-023.
In 2 of these trials—KEYNOTE-183 and -185—there were more deaths among patients receiving pembrolizumab than among patients receiving comparator treatments.
KEYNOTE-183 is a phase 3 study of pomalidomide and low-dose dexamethasone with or without pembrolizumab in refractory or relapsed and refractory MM.
KEYNOTE-185 is a phase 3 study of lenalidomide and low-dose dexamethasone with or without pembrolizumab in newly diagnosed and treatment-naïve MM.
The excess deaths in the pembrolizumab arms of KEYNOTE-183 and -185 led to a pause in enrollment for both trials, which was announced last month.
Now, the FDA says available data suggest the risks of pembrolizumab plus pomalidomide or lenalidomide outweigh any potential benefit for MM patients.
Therefore, all patients enrolled in KEYNOTE-183 and -185 will discontinue investigational treatment with pembrolizumab.
The same applies to patients in the pembrolizumab/lenalidomide/dexamethasone cohort of KEYNOTE-023.
KEYNOTE-023 is a phase 1 trial of pembrolizumab in combination with backbone treatments. Cohort 1 of this trial was designed to evaluate pembrolizumab in combination with lenalidomide and dexamethasone in MM patients who received prior treatment with an immunomodulatory agent (lenalidomide, pomalidomide, or thalidomide).
Pembrolizumab is a humanized monoclonal antibody that blocks interaction between the programmed cell death protein 1 (PD-1) and its receptor ligands, PD-L1 and PD-L2.
Pembrolizumab is FDA-approved to treat classical Hodgkin lymphoma, melanoma, non-small cell lung cancer, head and neck cancer, urothelial carcinoma, and microsatellite instability-high solid tumors.
EC approves therapy for relapsed/refractory BCP-ALL
The European Commission (EC) has approved inotuzumab ozogamicin (BESPONSA®) as monotherapy for adults with relapsed or refractory, CD22-positive B-cell precursor acute lymphoblastic leukemia (BCP-ALL).
Adults with Philadelphia chromosome-positive, relapsed/refractory, CD22-positive BCP-ALL should have failed treatment with at least one tyrosine kinase inhibitor before receiving inotuzumab ozogamicin.
Inotuzumab ozogamicin is an antibody-drug conjugate that consists of a monoclonal antibody targeting CD22 and a cytotoxic agent known as calicheamicin.
The product originates from a collaboration between Pfizer and Celltech (now UCB), but Pfizer has sole responsibility for all manufacturing and clinical development activities.
The EC’s approval of inotuzumab ozogamicin is supported by results from a phase 3 trial, which were published in NEJM in June 2016.
The trial enrolled 326 adult patients with relapsed or refractory BCP-ALL and compared inotuzumab ozogamicin to standard of care chemotherapy.
The rate of complete remission, including incomplete hematologic recovery, was 80.7% in the inotuzumab ozogamicin arm and 29.4% in the chemotherapy arm (P<0.001). The median duration of remission was 4.6 months and 3.1 months, respectively (P=0.03).
Forty-one percent of patients treated with inotuzumab ozogamicin and 11% of those who received chemotherapy proceeded to stem cell transplant directly after treatment (P<0.001).
The median progression-free survival was 5.0 months in the inotuzumab ozogamicin arm and 1.8 months in the chemotherapy arm (P<0.001).
The median overall survival was 7.7 months and 6.7 months, respectively (P=0.04). This did not meet the prespecified boundary of significance (P=0.0208).
Liver-related adverse events were more common in the inotuzumab ozogamicin arm than the chemotherapy arm. The most frequent of these were increased aspartate aminotransferase level (20% vs 10%), hyperbilirubinemia (15% vs 10%), and increased alanine aminotransferase level (14% vs 11%).
Veno-occlusive liver disease occurred in 11% of patients in the inotuzumab ozogamicin arm and 1% in the chemotherapy arm.
There were 17 deaths during treatment in the inotuzumab ozogamicin arm and 11 in the chemotherapy arm. Four deaths were considered related to inotuzumab ozogamicin, and 2 were thought to be related to chemotherapy.
The European Commission (EC) has approved inotuzumab ozogamicin (BESPONSA®) as monotherapy for adults with relapsed or refractory, CD22-positive B-cell precursor acute lymphoblastic leukemia (BCP-ALL).
Adults with Philadelphia chromosome-positive, relapsed/refractory, CD22-positive BCP-ALL should have failed treatment with at least one tyrosine kinase inhibitor before receiving inotuzumab ozogamicin.
Inotuzumab ozogamicin is an antibody-drug conjugate that consists of a monoclonal antibody targeting CD22 and a cytotoxic agent known as calicheamicin.
The product originates from a collaboration between Pfizer and Celltech (now UCB), but Pfizer has sole responsibility for all manufacturing and clinical development activities.
The EC’s approval of inotuzumab ozogamicin is supported by results from a phase 3 trial, which were published in NEJM in June 2016.
The trial enrolled 326 adult patients with relapsed or refractory BCP-ALL and compared inotuzumab ozogamicin to standard of care chemotherapy.
The rate of complete remission, including incomplete hematologic recovery, was 80.7% in the inotuzumab ozogamicin arm and 29.4% in the chemotherapy arm (P<0.001). The median duration of remission was 4.6 months and 3.1 months, respectively (P=0.03).
Forty-one percent of patients treated with inotuzumab ozogamicin and 11% of those who received chemotherapy proceeded to stem cell transplant directly after treatment (P<0.001).
The median progression-free survival was 5.0 months in the inotuzumab ozogamicin arm and 1.8 months in the chemotherapy arm (P<0.001).
The median overall survival was 7.7 months and 6.7 months, respectively (P=0.04). This did not meet the prespecified boundary of significance (P=0.0208).
Liver-related adverse events were more common in the inotuzumab ozogamicin arm than the chemotherapy arm. The most frequent of these were increased aspartate aminotransferase level (20% vs 10%), hyperbilirubinemia (15% vs 10%), and increased alanine aminotransferase level (14% vs 11%).
Veno-occlusive liver disease occurred in 11% of patients in the inotuzumab ozogamicin arm and 1% in the chemotherapy arm.
There were 17 deaths during treatment in the inotuzumab ozogamicin arm and 11 in the chemotherapy arm. Four deaths were considered related to inotuzumab ozogamicin, and 2 were thought to be related to chemotherapy.
The European Commission (EC) has approved inotuzumab ozogamicin (BESPONSA®) as monotherapy for adults with relapsed or refractory, CD22-positive B-cell precursor acute lymphoblastic leukemia (BCP-ALL).
Adults with Philadelphia chromosome-positive, relapsed/refractory, CD22-positive BCP-ALL should have failed treatment with at least one tyrosine kinase inhibitor before receiving inotuzumab ozogamicin.
Inotuzumab ozogamicin is an antibody-drug conjugate that consists of a monoclonal antibody targeting CD22 and a cytotoxic agent known as calicheamicin.
The product originates from a collaboration between Pfizer and Celltech (now UCB), but Pfizer has sole responsibility for all manufacturing and clinical development activities.
The EC’s approval of inotuzumab ozogamicin is supported by results from a phase 3 trial, which were published in NEJM in June 2016.
The trial enrolled 326 adult patients with relapsed or refractory BCP-ALL and compared inotuzumab ozogamicin to standard of care chemotherapy.
The rate of complete remission, including incomplete hematologic recovery, was 80.7% in the inotuzumab ozogamicin arm and 29.4% in the chemotherapy arm (P<0.001). The median duration of remission was 4.6 months and 3.1 months, respectively (P=0.03).
Forty-one percent of patients treated with inotuzumab ozogamicin and 11% of those who received chemotherapy proceeded to stem cell transplant directly after treatment (P<0.001).
The median progression-free survival was 5.0 months in the inotuzumab ozogamicin arm and 1.8 months in the chemotherapy arm (P<0.001).
The median overall survival was 7.7 months and 6.7 months, respectively (P=0.04). This did not meet the prespecified boundary of significance (P=0.0208).
Liver-related adverse events were more common in the inotuzumab ozogamicin arm than the chemotherapy arm. The most frequent of these were increased aspartate aminotransferase level (20% vs 10%), hyperbilirubinemia (15% vs 10%), and increased alanine aminotransferase level (14% vs 11%).
Veno-occlusive liver disease occurred in 11% of patients in the inotuzumab ozogamicin arm and 1% in the chemotherapy arm.
There were 17 deaths during treatment in the inotuzumab ozogamicin arm and 11 in the chemotherapy arm. Four deaths were considered related to inotuzumab ozogamicin, and 2 were thought to be related to chemotherapy.
FDA clears use of reagents to detect hematopoietic neoplasia
The US Food and Drug Administration (FDA) has allowed marketing of the ClearLLab Reagent Panel, a combination of conjugated antibody cocktails designed to aid the detection of hematopoietic neoplasia.
This includes chronic and acute leukemias, non-Hodgkin lymphoma, myeloma, myelodysplastic syndromes, and myeloproliferative neoplasms.
The ClearLLab reagents are intended for in vitro diagnostic use to identify various cell populations by immunophenotyping on an FC 500 flow cytometer.
The reagents are directed against B, T, and myeloid lineage antigens and intended to identify relevant leukocyte surface molecules.
ClearLLab provides 2 T-cell tubes, 2 B-cell tubes, and a myeloid tube, each consisting of pre-mixed 4- to 5-color cocktails. Together, this totals 18 markers as directly conjugated antibodies.
The reagents can be used with peripheral whole blood, bone marrow, and lymph node specimens.
The results obtained via testing with the ClearLLab reagents should be interpreted along with additional clinical and laboratory findings, according to Beckman Coulter, Inc., the company that will be marketing the reagents.
The FDA reviewed data for the ClearLLab reagents through the de novo premarket review pathway, a regulatory pathway for novel, low-to-moderate-risk devices that are not substantially equivalent to an already legally marketed device.
The FDA’s clearance of the ClearLLab reagents was supported by a study designed to demonstrate the reagents’ performance, which was conducted on 279 samples at 4 independent clinical sites.
Results with the ClearLLab reagents were compared to results with alternative detection methods used at the sites.
The ClearLLab results aligned with the study sites’ final diagnosis 93.4% of the time and correctly detected abnormalities 84.2% of the time.
Along with its clearance of the ClearLLab reagents, the FDA is establishing criteria, called special controls, which clarify the agency’s expectations in assuring the reagents’ accuracy, reliability, and clinical relevance.
These special controls, when met along with general controls, provide reasonable assurance of safety and effectiveness for the ClearLLab reagents and similar tools.
The special controls also describe the least burdensome regulatory pathway for future developers of similar diagnostic tests.
The US Food and Drug Administration (FDA) has allowed marketing of the ClearLLab Reagent Panel, a combination of conjugated antibody cocktails designed to aid the detection of hematopoietic neoplasia.
This includes chronic and acute leukemias, non-Hodgkin lymphoma, myeloma, myelodysplastic syndromes, and myeloproliferative neoplasms.
The ClearLLab reagents are intended for in vitro diagnostic use to identify various cell populations by immunophenotyping on an FC 500 flow cytometer.
The reagents are directed against B, T, and myeloid lineage antigens and intended to identify relevant leukocyte surface molecules.
ClearLLab provides 2 T-cell tubes, 2 B-cell tubes, and a myeloid tube, each consisting of pre-mixed 4- to 5-color cocktails. Together, this totals 18 markers as directly conjugated antibodies.
The reagents can be used with peripheral whole blood, bone marrow, and lymph node specimens.
The results obtained via testing with the ClearLLab reagents should be interpreted along with additional clinical and laboratory findings, according to Beckman Coulter, Inc., the company that will be marketing the reagents.
The FDA reviewed data for the ClearLLab reagents through the de novo premarket review pathway, a regulatory pathway for novel, low-to-moderate-risk devices that are not substantially equivalent to an already legally marketed device.
The FDA’s clearance of the ClearLLab reagents was supported by a study designed to demonstrate the reagents’ performance, which was conducted on 279 samples at 4 independent clinical sites.
Results with the ClearLLab reagents were compared to results with alternative detection methods used at the sites.
The ClearLLab results aligned with the study sites’ final diagnosis 93.4% of the time and correctly detected abnormalities 84.2% of the time.
Along with its clearance of the ClearLLab reagents, the FDA is establishing criteria, called special controls, which clarify the agency’s expectations in assuring the reagents’ accuracy, reliability, and clinical relevance.
These special controls, when met along with general controls, provide reasonable assurance of safety and effectiveness for the ClearLLab reagents and similar tools.
The special controls also describe the least burdensome regulatory pathway for future developers of similar diagnostic tests.
The US Food and Drug Administration (FDA) has allowed marketing of the ClearLLab Reagent Panel, a combination of conjugated antibody cocktails designed to aid the detection of hematopoietic neoplasia.
This includes chronic and acute leukemias, non-Hodgkin lymphoma, myeloma, myelodysplastic syndromes, and myeloproliferative neoplasms.
The ClearLLab reagents are intended for in vitro diagnostic use to identify various cell populations by immunophenotyping on an FC 500 flow cytometer.
The reagents are directed against B, T, and myeloid lineage antigens and intended to identify relevant leukocyte surface molecules.
ClearLLab provides 2 T-cell tubes, 2 B-cell tubes, and a myeloid tube, each consisting of pre-mixed 4- to 5-color cocktails. Together, this totals 18 markers as directly conjugated antibodies.
The reagents can be used with peripheral whole blood, bone marrow, and lymph node specimens.
The results obtained via testing with the ClearLLab reagents should be interpreted along with additional clinical and laboratory findings, according to Beckman Coulter, Inc., the company that will be marketing the reagents.
The FDA reviewed data for the ClearLLab reagents through the de novo premarket review pathway, a regulatory pathway for novel, low-to-moderate-risk devices that are not substantially equivalent to an already legally marketed device.
The FDA’s clearance of the ClearLLab reagents was supported by a study designed to demonstrate the reagents’ performance, which was conducted on 279 samples at 4 independent clinical sites.
Results with the ClearLLab reagents were compared to results with alternative detection methods used at the sites.
The ClearLLab results aligned with the study sites’ final diagnosis 93.4% of the time and correctly detected abnormalities 84.2% of the time.
Along with its clearance of the ClearLLab reagents, the FDA is establishing criteria, called special controls, which clarify the agency’s expectations in assuring the reagents’ accuracy, reliability, and clinical relevance.
These special controls, when met along with general controls, provide reasonable assurance of safety and effectiveness for the ClearLLab reagents and similar tools.
The special controls also describe the least burdensome regulatory pathway for future developers of similar diagnostic tests.
Drug granted PRIME access as treatment for DLBCL
The European Medicines Agency (EMA) has granted polatuzumab vedotin access to the agency’s PRIority MEdicines (PRIME) program.
The access is for polatuzumab vedotin when used in combination with rituximab and bendamustine for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL).
Polatuzumab vedotin is an anti-CD79b antibody drug conjugate consisting of an anti-CD79b monoclonal antibody that is linked to a microtubule-disrupting agent.
Polatuzumab vedotin is being developed by Roche utilizing Seattle Genetics’ technology.
The goal of the EMA’s PRIME program is to accelerate the development of therapies that may offer a major advantage over existing treatments or benefit patients with no treatment options.
Through PRIME, the EMA offers early and enhanced support to developers in order to optimize development plans and speed regulatory evaluations to potentially bring therapies to patients more quickly.
To be accepted for PRIME, a therapy must demonstrate the potential to benefit patients with unmet medical need through early clinical or nonclinical data.
The acceptance of polatuzumab vedotin in the PRIME program was supported by results from the phase 2 component of the GO29365 study.
Results from this trial were recently presented at the 22nd Congress of the European Hematology Association (EHA) as abstract S468.
The European Medicines Agency (EMA) has granted polatuzumab vedotin access to the agency’s PRIority MEdicines (PRIME) program.
The access is for polatuzumab vedotin when used in combination with rituximab and bendamustine for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL).
Polatuzumab vedotin is an anti-CD79b antibody drug conjugate consisting of an anti-CD79b monoclonal antibody that is linked to a microtubule-disrupting agent.
Polatuzumab vedotin is being developed by Roche utilizing Seattle Genetics’ technology.
The goal of the EMA’s PRIME program is to accelerate the development of therapies that may offer a major advantage over existing treatments or benefit patients with no treatment options.
Through PRIME, the EMA offers early and enhanced support to developers in order to optimize development plans and speed regulatory evaluations to potentially bring therapies to patients more quickly.
To be accepted for PRIME, a therapy must demonstrate the potential to benefit patients with unmet medical need through early clinical or nonclinical data.
The acceptance of polatuzumab vedotin in the PRIME program was supported by results from the phase 2 component of the GO29365 study.
Results from this trial were recently presented at the 22nd Congress of the European Hematology Association (EHA) as abstract S468.
The European Medicines Agency (EMA) has granted polatuzumab vedotin access to the agency’s PRIority MEdicines (PRIME) program.
The access is for polatuzumab vedotin when used in combination with rituximab and bendamustine for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL).
Polatuzumab vedotin is an anti-CD79b antibody drug conjugate consisting of an anti-CD79b monoclonal antibody that is linked to a microtubule-disrupting agent.
Polatuzumab vedotin is being developed by Roche utilizing Seattle Genetics’ technology.
The goal of the EMA’s PRIME program is to accelerate the development of therapies that may offer a major advantage over existing treatments or benefit patients with no treatment options.
Through PRIME, the EMA offers early and enhanced support to developers in order to optimize development plans and speed regulatory evaluations to potentially bring therapies to patients more quickly.
To be accepted for PRIME, a therapy must demonstrate the potential to benefit patients with unmet medical need through early clinical or nonclinical data.
The acceptance of polatuzumab vedotin in the PRIME program was supported by results from the phase 2 component of the GO29365 study.
Results from this trial were recently presented at the 22nd Congress of the European Hematology Association (EHA) as abstract S468.
FDA unveils plan to eliminate orphan designation backlog
The US Food and Drug Administration (FDA) has unveiled a plan to eliminate the agency’s existing backlog of orphan designation requests and ensure timely responses to all new requests with firm deadlines.
The agency’s Orphan Drug Modernization Plan comes a week after FDA Commissioner Scott Gottlieb committed to eliminating the backlog within 90 days and responding to all new requests for designation within 90 days of receipt during his testimony before a Senate subcommittee.
As authorized under the Orphan Drug Act, the Orphan Drug Designation Program provides orphan status to drugs and biologics intended for the treatment, diagnosis, or prevention of rare diseases, which are generally defined as diseases that affect fewer than 200,000 people in the US.
Orphan designation qualifies a product’s developer for various development incentives, including tax credits for clinical trial costs, relief from prescription drug user fee if the indication is for a rare disease or condition, and eligibility for 7 years of marketing exclusivity if the product is approved.
A request for orphan designation is one step that can be taken in the development process and is different than the filing of a marketing application with the FDA.
Currently, the FDA has about 200 orphan drug designation requests that are pending review. The number of orphan drug designation requests has steadily increased over the past 5 years.
In 2016, the FDA’s Office of Orphan Products Development received 568 new requests for designation – more than double the number of requests received in 2012.
The FDA says this increased interest in the program is a positive development for patients with rare diseases, and, with the Orphan Drug Modernization Plan, the FDA is committing to advancing the program to ensure it can efficiently and adequately review these requests.
“People who suffer with rare diseases are too often faced with no or limited treatment options, and what treatment options they have may be quite expensive due, in part, to significant costs of developing therapies for smaller populations,” said FDA Commissioner Scott Gottlieb, MD.
“Congress gave us tools to incentivize the development of novel therapies for rare diseases, and we intend to use these resources to their fullest extent in order to ensure Americans get the safe and effective medicines they need, and that the process for developing these innovations is as modern and efficient as possible.”
Among the elements of the Orphan Drug Modernization Plan, the FDA will deploy a Backlog SWAT team comprised of senior, experienced reviewers with significant expertise in orphan drug designation. The team will focus solely on the backlogged applications, starting with the oldest requests.
The agency will also employ a streamlined Designation Review Template to increase consistency and efficiency of its reviews.
In addition, the Orphan Drug Designation Program will look to collaborate within the agency’s medical product centers to create greater efficiency, including conducting joint reviews with the Office of Pediatric Therapeutics to review rare pediatric disease designation requests.
To ensure all future requests receive a response within 90 days of receipt, the FDA will take a multifaceted approach.
These efforts include, among other new steps:
- Reorganizing the review staff to maximize expertise and improve workload efficiencies
- Better leveraging the expertise across the FDA’s medical product centers
- Establishing a new FDA Orphan Products Council that will help address scientific and regulatory issues to ensure the agency is applying a consistent approach to regulating orphan drug products and reviewing designation requests.
The FDA is planning for the backlog to be eliminated by mid-September.
The Orphan Drug Modernization Plan is the first element of several efforts the FDA plans to undertake under its new “Medical Innovation Development Plan,” which is aimed at ensuring the FDA’s regulatory tools and policies are modern, risk-based, and efficient.
The goal of the plan is to seek ways the FDA can help facilitate the development of safe, effective, and transformative medical innovations that have the potential to significantly impact disease and reduce overall healthcare costs.
The US Food and Drug Administration (FDA) has unveiled a plan to eliminate the agency’s existing backlog of orphan designation requests and ensure timely responses to all new requests with firm deadlines.
The agency’s Orphan Drug Modernization Plan comes a week after FDA Commissioner Scott Gottlieb committed to eliminating the backlog within 90 days and responding to all new requests for designation within 90 days of receipt during his testimony before a Senate subcommittee.
As authorized under the Orphan Drug Act, the Orphan Drug Designation Program provides orphan status to drugs and biologics intended for the treatment, diagnosis, or prevention of rare diseases, which are generally defined as diseases that affect fewer than 200,000 people in the US.
Orphan designation qualifies a product’s developer for various development incentives, including tax credits for clinical trial costs, relief from prescription drug user fee if the indication is for a rare disease or condition, and eligibility for 7 years of marketing exclusivity if the product is approved.
A request for orphan designation is one step that can be taken in the development process and is different than the filing of a marketing application with the FDA.
Currently, the FDA has about 200 orphan drug designation requests that are pending review. The number of orphan drug designation requests has steadily increased over the past 5 years.
In 2016, the FDA’s Office of Orphan Products Development received 568 new requests for designation – more than double the number of requests received in 2012.
The FDA says this increased interest in the program is a positive development for patients with rare diseases, and, with the Orphan Drug Modernization Plan, the FDA is committing to advancing the program to ensure it can efficiently and adequately review these requests.
“People who suffer with rare diseases are too often faced with no or limited treatment options, and what treatment options they have may be quite expensive due, in part, to significant costs of developing therapies for smaller populations,” said FDA Commissioner Scott Gottlieb, MD.
“Congress gave us tools to incentivize the development of novel therapies for rare diseases, and we intend to use these resources to their fullest extent in order to ensure Americans get the safe and effective medicines they need, and that the process for developing these innovations is as modern and efficient as possible.”
Among the elements of the Orphan Drug Modernization Plan, the FDA will deploy a Backlog SWAT team comprised of senior, experienced reviewers with significant expertise in orphan drug designation. The team will focus solely on the backlogged applications, starting with the oldest requests.
The agency will also employ a streamlined Designation Review Template to increase consistency and efficiency of its reviews.
In addition, the Orphan Drug Designation Program will look to collaborate within the agency’s medical product centers to create greater efficiency, including conducting joint reviews with the Office of Pediatric Therapeutics to review rare pediatric disease designation requests.
To ensure all future requests receive a response within 90 days of receipt, the FDA will take a multifaceted approach.
These efforts include, among other new steps:
- Reorganizing the review staff to maximize expertise and improve workload efficiencies
- Better leveraging the expertise across the FDA’s medical product centers
- Establishing a new FDA Orphan Products Council that will help address scientific and regulatory issues to ensure the agency is applying a consistent approach to regulating orphan drug products and reviewing designation requests.
The FDA is planning for the backlog to be eliminated by mid-September.
The Orphan Drug Modernization Plan is the first element of several efforts the FDA plans to undertake under its new “Medical Innovation Development Plan,” which is aimed at ensuring the FDA’s regulatory tools and policies are modern, risk-based, and efficient.
The goal of the plan is to seek ways the FDA can help facilitate the development of safe, effective, and transformative medical innovations that have the potential to significantly impact disease and reduce overall healthcare costs.
The US Food and Drug Administration (FDA) has unveiled a plan to eliminate the agency’s existing backlog of orphan designation requests and ensure timely responses to all new requests with firm deadlines.
The agency’s Orphan Drug Modernization Plan comes a week after FDA Commissioner Scott Gottlieb committed to eliminating the backlog within 90 days and responding to all new requests for designation within 90 days of receipt during his testimony before a Senate subcommittee.
As authorized under the Orphan Drug Act, the Orphan Drug Designation Program provides orphan status to drugs and biologics intended for the treatment, diagnosis, or prevention of rare diseases, which are generally defined as diseases that affect fewer than 200,000 people in the US.
Orphan designation qualifies a product’s developer for various development incentives, including tax credits for clinical trial costs, relief from prescription drug user fee if the indication is for a rare disease or condition, and eligibility for 7 years of marketing exclusivity if the product is approved.
A request for orphan designation is one step that can be taken in the development process and is different than the filing of a marketing application with the FDA.
Currently, the FDA has about 200 orphan drug designation requests that are pending review. The number of orphan drug designation requests has steadily increased over the past 5 years.
In 2016, the FDA’s Office of Orphan Products Development received 568 new requests for designation – more than double the number of requests received in 2012.
The FDA says this increased interest in the program is a positive development for patients with rare diseases, and, with the Orphan Drug Modernization Plan, the FDA is committing to advancing the program to ensure it can efficiently and adequately review these requests.
“People who suffer with rare diseases are too often faced with no or limited treatment options, and what treatment options they have may be quite expensive due, in part, to significant costs of developing therapies for smaller populations,” said FDA Commissioner Scott Gottlieb, MD.
“Congress gave us tools to incentivize the development of novel therapies for rare diseases, and we intend to use these resources to their fullest extent in order to ensure Americans get the safe and effective medicines they need, and that the process for developing these innovations is as modern and efficient as possible.”
Among the elements of the Orphan Drug Modernization Plan, the FDA will deploy a Backlog SWAT team comprised of senior, experienced reviewers with significant expertise in orphan drug designation. The team will focus solely on the backlogged applications, starting with the oldest requests.
The agency will also employ a streamlined Designation Review Template to increase consistency and efficiency of its reviews.
In addition, the Orphan Drug Designation Program will look to collaborate within the agency’s medical product centers to create greater efficiency, including conducting joint reviews with the Office of Pediatric Therapeutics to review rare pediatric disease designation requests.
To ensure all future requests receive a response within 90 days of receipt, the FDA will take a multifaceted approach.
These efforts include, among other new steps:
- Reorganizing the review staff to maximize expertise and improve workload efficiencies
- Better leveraging the expertise across the FDA’s medical product centers
- Establishing a new FDA Orphan Products Council that will help address scientific and regulatory issues to ensure the agency is applying a consistent approach to regulating orphan drug products and reviewing designation requests.
The FDA is planning for the backlog to be eliminated by mid-September.
The Orphan Drug Modernization Plan is the first element of several efforts the FDA plans to undertake under its new “Medical Innovation Development Plan,” which is aimed at ensuring the FDA’s regulatory tools and policies are modern, risk-based, and efficient.
The goal of the plan is to seek ways the FDA can help facilitate the development of safe, effective, and transformative medical innovations that have the potential to significantly impact disease and reduce overall healthcare costs.