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FDA approves venetoclax for CLL/SLL with or without del 17p
The US Food and Drug Administration (FDA) has approved venetoclax tablets (Venclexta ®) in combination with rituximab to treat patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have received 1 prior therapy.
The combination is approved for patients with or without deletion of 17p (del 17p).
The FDA based its approval on the phase 3 MURANO trial, in which venetoclax in combination with rituximab (VEN+R) significantly improved progression-free survival (PFS) in relapsed or refractory CLL patients compared to the chemoimmunotherapy regimen of bendamustine plus rituximab(B+R).
This approval, according to the drug’s developers, makes venetoclax plus rituximab the first oral-based, chemotherapy-free combination with a fixed treatment duration for CLL.
The FDA has also converted venetoclax's accelerated approval to a full approval. The drug was previously granted accelerated approval as a single agent for the treatment of people with CLL with 17p deletion.
Venetoclax is being developed by AbbVie and Roche and jointly commercialized by AbbVie and Genentech in the US and by AbbVie outside the US.
Phase 3 MURANO trial (NCT02005471)
The multicenter, open-label trial randomized 389 patients to VEN+R (194 patients) or B+R (195 patients). Median age of the patients was 65 years (range, 22 – 85).
Patients in the VEN+R arm completed a 5-week ramp-up of venetoclax followed by venetoclax 400 mg once daily for 24 months measured from the rituximab start date.
Tumor lysis syndrome (TLS), caused by a rapid reduction in tumor volume, is an identified risk with venetoclax treatment. The dose ramp-up was intended to mitigate this risk.
Rituximab was initiated after venetoclax ramp-up and given for 6 cycles (375 mg/m2 intravenously on cycle 1 day 1 and 500 mg/m2 intravenously on day 1 of cycles 2-6, with a 28-day cycle length).
Patients in the B+R arm received 6 cycles of B+R (bendamustine 70 mg/m2 on days 1 and 2 of each 28-day cycle and rituximab at the above described dose and schedule).
Efficacy was based on PFS as assessed by an independent review committee.
After a median follow-up of 23 months, the median PFS was not reached in the VEN+R arm and was 18.1 months in the B+R arm (P<0.0001).
The overall response rate was 92% for patients treated with VEN+R compared to 72% for those treated with B+R.
Safety
The most common adverse events (AEs) in the VEN+R arms that occurred in 20% or more patients were neutropenia (65%), diarrhea (40%), upper respiratory tract infection (39%), fatigue (22%), cough (22%), and nausea (21%).
Grade 3 or 4 neutropenia developed in 64% of patients, and grade 4 neutropenia in 31%.
Serious adverse events (SAEs) developed in 46% of patients and serious infections in 21%, consisting most frequently of pneumonia (9%).
The incidence of TLS was 3%, occurring in 6 of 194 patients.
In the VEN+R arm, discontinuations due to any AEs occurred in 16% of patients, dose reductions in 15%, and dose interruptions in 71%.
Neutropenia led to dose interruptions in 46% of patients and discontinuations in 3%. Thrombocytopenia led to discontinuations in 3% of patients.
Fatal AEs that occurred in the absence of disease progression and within 30 days of the last VEN+R treatment and/or 90 days of the last rituximab infusion were reported in 2% (4/194) of patients.
In the B+R arm, AEs led to treatment discontinuations in 10% of patients, dose reductions in 15%, and dose interruptions in 40 %.
Investigators previously reported data from the phase 3 MURANO study as a late-breaking abstract at the 2017 ASH Annual Meeting and published the findings in NEJM.
John Seymour, MBBS, PhD, lead investigator of the MURANO study, said in the corporate release, the approval "validates the results seen in the phase 3 trial, including the significant improvement in progression-free survival over a standard of care comparator arm."
"Progression-free survival is considered a gold standard for demonstrating clinical benefit in oncology," he added.
Full prescribing information for venetoclax is available here.
The US Food and Drug Administration (FDA) has approved venetoclax tablets (Venclexta ®) in combination with rituximab to treat patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have received 1 prior therapy.
The combination is approved for patients with or without deletion of 17p (del 17p).
The FDA based its approval on the phase 3 MURANO trial, in which venetoclax in combination with rituximab (VEN+R) significantly improved progression-free survival (PFS) in relapsed or refractory CLL patients compared to the chemoimmunotherapy regimen of bendamustine plus rituximab(B+R).
This approval, according to the drug’s developers, makes venetoclax plus rituximab the first oral-based, chemotherapy-free combination with a fixed treatment duration for CLL.
The FDA has also converted venetoclax's accelerated approval to a full approval. The drug was previously granted accelerated approval as a single agent for the treatment of people with CLL with 17p deletion.
Venetoclax is being developed by AbbVie and Roche and jointly commercialized by AbbVie and Genentech in the US and by AbbVie outside the US.
Phase 3 MURANO trial (NCT02005471)
The multicenter, open-label trial randomized 389 patients to VEN+R (194 patients) or B+R (195 patients). Median age of the patients was 65 years (range, 22 – 85).
Patients in the VEN+R arm completed a 5-week ramp-up of venetoclax followed by venetoclax 400 mg once daily for 24 months measured from the rituximab start date.
Tumor lysis syndrome (TLS), caused by a rapid reduction in tumor volume, is an identified risk with venetoclax treatment. The dose ramp-up was intended to mitigate this risk.
Rituximab was initiated after venetoclax ramp-up and given for 6 cycles (375 mg/m2 intravenously on cycle 1 day 1 and 500 mg/m2 intravenously on day 1 of cycles 2-6, with a 28-day cycle length).
Patients in the B+R arm received 6 cycles of B+R (bendamustine 70 mg/m2 on days 1 and 2 of each 28-day cycle and rituximab at the above described dose and schedule).
Efficacy was based on PFS as assessed by an independent review committee.
After a median follow-up of 23 months, the median PFS was not reached in the VEN+R arm and was 18.1 months in the B+R arm (P<0.0001).
The overall response rate was 92% for patients treated with VEN+R compared to 72% for those treated with B+R.
Safety
The most common adverse events (AEs) in the VEN+R arms that occurred in 20% or more patients were neutropenia (65%), diarrhea (40%), upper respiratory tract infection (39%), fatigue (22%), cough (22%), and nausea (21%).
Grade 3 or 4 neutropenia developed in 64% of patients, and grade 4 neutropenia in 31%.
Serious adverse events (SAEs) developed in 46% of patients and serious infections in 21%, consisting most frequently of pneumonia (9%).
The incidence of TLS was 3%, occurring in 6 of 194 patients.
In the VEN+R arm, discontinuations due to any AEs occurred in 16% of patients, dose reductions in 15%, and dose interruptions in 71%.
Neutropenia led to dose interruptions in 46% of patients and discontinuations in 3%. Thrombocytopenia led to discontinuations in 3% of patients.
Fatal AEs that occurred in the absence of disease progression and within 30 days of the last VEN+R treatment and/or 90 days of the last rituximab infusion were reported in 2% (4/194) of patients.
In the B+R arm, AEs led to treatment discontinuations in 10% of patients, dose reductions in 15%, and dose interruptions in 40 %.
Investigators previously reported data from the phase 3 MURANO study as a late-breaking abstract at the 2017 ASH Annual Meeting and published the findings in NEJM.
John Seymour, MBBS, PhD, lead investigator of the MURANO study, said in the corporate release, the approval "validates the results seen in the phase 3 trial, including the significant improvement in progression-free survival over a standard of care comparator arm."
"Progression-free survival is considered a gold standard for demonstrating clinical benefit in oncology," he added.
Full prescribing information for venetoclax is available here.
The US Food and Drug Administration (FDA) has approved venetoclax tablets (Venclexta ®) in combination with rituximab to treat patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have received 1 prior therapy.
The combination is approved for patients with or without deletion of 17p (del 17p).
The FDA based its approval on the phase 3 MURANO trial, in which venetoclax in combination with rituximab (VEN+R) significantly improved progression-free survival (PFS) in relapsed or refractory CLL patients compared to the chemoimmunotherapy regimen of bendamustine plus rituximab(B+R).
This approval, according to the drug’s developers, makes venetoclax plus rituximab the first oral-based, chemotherapy-free combination with a fixed treatment duration for CLL.
The FDA has also converted venetoclax's accelerated approval to a full approval. The drug was previously granted accelerated approval as a single agent for the treatment of people with CLL with 17p deletion.
Venetoclax is being developed by AbbVie and Roche and jointly commercialized by AbbVie and Genentech in the US and by AbbVie outside the US.
Phase 3 MURANO trial (NCT02005471)
The multicenter, open-label trial randomized 389 patients to VEN+R (194 patients) or B+R (195 patients). Median age of the patients was 65 years (range, 22 – 85).
Patients in the VEN+R arm completed a 5-week ramp-up of venetoclax followed by venetoclax 400 mg once daily for 24 months measured from the rituximab start date.
Tumor lysis syndrome (TLS), caused by a rapid reduction in tumor volume, is an identified risk with venetoclax treatment. The dose ramp-up was intended to mitigate this risk.
Rituximab was initiated after venetoclax ramp-up and given for 6 cycles (375 mg/m2 intravenously on cycle 1 day 1 and 500 mg/m2 intravenously on day 1 of cycles 2-6, with a 28-day cycle length).
Patients in the B+R arm received 6 cycles of B+R (bendamustine 70 mg/m2 on days 1 and 2 of each 28-day cycle and rituximab at the above described dose and schedule).
Efficacy was based on PFS as assessed by an independent review committee.
After a median follow-up of 23 months, the median PFS was not reached in the VEN+R arm and was 18.1 months in the B+R arm (P<0.0001).
The overall response rate was 92% for patients treated with VEN+R compared to 72% for those treated with B+R.
Safety
The most common adverse events (AEs) in the VEN+R arms that occurred in 20% or more patients were neutropenia (65%), diarrhea (40%), upper respiratory tract infection (39%), fatigue (22%), cough (22%), and nausea (21%).
Grade 3 or 4 neutropenia developed in 64% of patients, and grade 4 neutropenia in 31%.
Serious adverse events (SAEs) developed in 46% of patients and serious infections in 21%, consisting most frequently of pneumonia (9%).
The incidence of TLS was 3%, occurring in 6 of 194 patients.
In the VEN+R arm, discontinuations due to any AEs occurred in 16% of patients, dose reductions in 15%, and dose interruptions in 71%.
Neutropenia led to dose interruptions in 46% of patients and discontinuations in 3%. Thrombocytopenia led to discontinuations in 3% of patients.
Fatal AEs that occurred in the absence of disease progression and within 30 days of the last VEN+R treatment and/or 90 days of the last rituximab infusion were reported in 2% (4/194) of patients.
In the B+R arm, AEs led to treatment discontinuations in 10% of patients, dose reductions in 15%, and dose interruptions in 40 %.
Investigators previously reported data from the phase 3 MURANO study as a late-breaking abstract at the 2017 ASH Annual Meeting and published the findings in NEJM.
John Seymour, MBBS, PhD, lead investigator of the MURANO study, said in the corporate release, the approval "validates the results seen in the phase 3 trial, including the significant improvement in progression-free survival over a standard of care comparator arm."
"Progression-free survival is considered a gold standard for demonstrating clinical benefit in oncology," he added.
Full prescribing information for venetoclax is available here.
FDA grants regular approval to venetoclax for CLL/SLL
Venetoclax (Venclexta) has received regular approval from the Food and Drug Administration for the treatment of patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), with or without 17p deletion, who have received at least one prior therapy.
The approval was based results from the MURANO trial of 389 patients, which was a randomized, multicenter, open-label trial of venetoclax plus rituximab versus bendamustine plus rituximab.
Neutropenia, diarrhea, upper respiratory tract infection, fatigue, cough, and nausea were the most common adverse events seen in the venetoclax arm. Grade 3 or 4 neutropenia developed in 64% of those patients, and grade 4 in 31%. The most common infection in venetoclax patients was pneumonia, but overall, 21% of patients in that arm experienced some kind of infection.
Because of the rapid reduction in tumor size, tumor lysis syndrome is possible with venetoclax treatment, the FDA noted.
In 2016, the FDA granted accelerated approval to venetoclax for treatment of patients with CLL with 17d deletion who had received at least one prior line of therapy.
Venetoclax (Venclexta) has received regular approval from the Food and Drug Administration for the treatment of patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), with or without 17p deletion, who have received at least one prior therapy.
The approval was based results from the MURANO trial of 389 patients, which was a randomized, multicenter, open-label trial of venetoclax plus rituximab versus bendamustine plus rituximab.
Neutropenia, diarrhea, upper respiratory tract infection, fatigue, cough, and nausea were the most common adverse events seen in the venetoclax arm. Grade 3 or 4 neutropenia developed in 64% of those patients, and grade 4 in 31%. The most common infection in venetoclax patients was pneumonia, but overall, 21% of patients in that arm experienced some kind of infection.
Because of the rapid reduction in tumor size, tumor lysis syndrome is possible with venetoclax treatment, the FDA noted.
In 2016, the FDA granted accelerated approval to venetoclax for treatment of patients with CLL with 17d deletion who had received at least one prior line of therapy.
Venetoclax (Venclexta) has received regular approval from the Food and Drug Administration for the treatment of patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), with or without 17p deletion, who have received at least one prior therapy.
The approval was based results from the MURANO trial of 389 patients, which was a randomized, multicenter, open-label trial of venetoclax plus rituximab versus bendamustine plus rituximab.
Neutropenia, diarrhea, upper respiratory tract infection, fatigue, cough, and nausea were the most common adverse events seen in the venetoclax arm. Grade 3 or 4 neutropenia developed in 64% of those patients, and grade 4 in 31%. The most common infection in venetoclax patients was pneumonia, but overall, 21% of patients in that arm experienced some kind of infection.
Because of the rapid reduction in tumor size, tumor lysis syndrome is possible with venetoclax treatment, the FDA noted.
In 2016, the FDA granted accelerated approval to venetoclax for treatment of patients with CLL with 17d deletion who had received at least one prior line of therapy.
Venetoclax plus ibrutinib yields encouraging MRD results in first-line CLL
CHICAGO – The combination of ibrutinib plus venetoclax yielded a high rate of undetectable minimal residual disease (MRD) when used as first-line treatment for chronic lymphocytic leukemia (CLL), according to preliminary results of the CAPTIVATE trial.
Of the first 30 patients in the trial, 23 (77%) had undetectable blood MRD after just six cycles of combined treatment, said investigator William G. Wierda, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston.
“These early results show a highly active and safe treatment with 12 cycles of combined treatment with ibrutinib and venetoclax,” Dr. Wierda said in a presentation of the CAPTIVATE results at the annual meeting of the American Society of Clinical Oncology.
Those MRD results are “at least as good as we can achieve with chemoimmunotherapy,” Bruce D. Cheson, MD, head of hematology at Georgetown University, Washington, said during a discussion of the CAPTIVATE study results.
Dr. Cheson referenced MRD results from a 2016 analysis of the CLL8 and CLL10 trials, which included patients treated with fludarabine, cyclophosphamide, and rituximab (FCR) and bendamustine plus rituximab (BR). In that analysis, 33.6% of patients achieved MRD-negative complete response and 29.1% achieved MRD-negative partial response.
In CAPTIVATE, by contrast, all of the complete remissions were MRD negative, as were a majority of the partial responders, Dr. Cheson noted.
Venetoclax and ibrutinib have “clinically complimentary activity” that provided a rationale for combining the two, Dr. Wierda said at ASCO. Ibrutinib is a BTK inhibitor that has a high rate of response and durable disease control, though continuous treatment is indicated, he said, because most patients achieve partial remissions as best response and continue to have residual disease in blood or bone marrow. Venetoclax, he added, is a BCL-2 inhibitor that produces durable partial remissions, though “residual disease is typically present in the form of persistently enlarged lymph nodes,” he said. “Venetoclax is highly effective at clearing disease from blood and bone marrow.”
The phase 2 CAPTIVATE trial includes a total of 164 patients younger than 70 years of age who receive a 3-cycle ibrutinib lead-in, followed by ibrutinib plus venetoclax for 12 cycles. At that point, patients are randomized according to MRD status. Patients with confirmed undetectable MRD are randomized to further treatment with ibrutinib or placebo, and those with undetectable MRD not confirmed are randomized to ibrutinib versus ibrutinib plus venetoclax.
In addition to early efficacy data, Dr. Wierda also reported some safety data. Compared with the single-agent ibrutinib lead-in period, combined ibrutinib plus venetoclax treatment had more gastrointestinal-associated events and neutropenia. Almost half of patients (45%) have had a treatment-related grade 3-4 adverse event, though just 18 (11%) have had treatment-related adverse events classified as serious, and there have been no adverse event-related deaths on study.
The high activity of ibrutinib plus venetoclax in CAPTIVATE supports further study of the combination, Dr. Wierda said. A randomized, open-label phase 3 trial of ibrutinib plus venetoclax versus chlorambucil plus obinutuzumab as first-line treatment for CLL is currently recruiting.
The study was sponsored by Pharmacyclics, an AbbVie company. Dr. Wierda reported consulting and research funding from Pharmacyclics, AbbVie, and several other companies.
SOURCE: Wierda WG et al. ASCO 2018, Abstract 7502.
CHICAGO – The combination of ibrutinib plus venetoclax yielded a high rate of undetectable minimal residual disease (MRD) when used as first-line treatment for chronic lymphocytic leukemia (CLL), according to preliminary results of the CAPTIVATE trial.
Of the first 30 patients in the trial, 23 (77%) had undetectable blood MRD after just six cycles of combined treatment, said investigator William G. Wierda, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston.
“These early results show a highly active and safe treatment with 12 cycles of combined treatment with ibrutinib and venetoclax,” Dr. Wierda said in a presentation of the CAPTIVATE results at the annual meeting of the American Society of Clinical Oncology.
Those MRD results are “at least as good as we can achieve with chemoimmunotherapy,” Bruce D. Cheson, MD, head of hematology at Georgetown University, Washington, said during a discussion of the CAPTIVATE study results.
Dr. Cheson referenced MRD results from a 2016 analysis of the CLL8 and CLL10 trials, which included patients treated with fludarabine, cyclophosphamide, and rituximab (FCR) and bendamustine plus rituximab (BR). In that analysis, 33.6% of patients achieved MRD-negative complete response and 29.1% achieved MRD-negative partial response.
In CAPTIVATE, by contrast, all of the complete remissions were MRD negative, as were a majority of the partial responders, Dr. Cheson noted.
Venetoclax and ibrutinib have “clinically complimentary activity” that provided a rationale for combining the two, Dr. Wierda said at ASCO. Ibrutinib is a BTK inhibitor that has a high rate of response and durable disease control, though continuous treatment is indicated, he said, because most patients achieve partial remissions as best response and continue to have residual disease in blood or bone marrow. Venetoclax, he added, is a BCL-2 inhibitor that produces durable partial remissions, though “residual disease is typically present in the form of persistently enlarged lymph nodes,” he said. “Venetoclax is highly effective at clearing disease from blood and bone marrow.”
The phase 2 CAPTIVATE trial includes a total of 164 patients younger than 70 years of age who receive a 3-cycle ibrutinib lead-in, followed by ibrutinib plus venetoclax for 12 cycles. At that point, patients are randomized according to MRD status. Patients with confirmed undetectable MRD are randomized to further treatment with ibrutinib or placebo, and those with undetectable MRD not confirmed are randomized to ibrutinib versus ibrutinib plus venetoclax.
In addition to early efficacy data, Dr. Wierda also reported some safety data. Compared with the single-agent ibrutinib lead-in period, combined ibrutinib plus venetoclax treatment had more gastrointestinal-associated events and neutropenia. Almost half of patients (45%) have had a treatment-related grade 3-4 adverse event, though just 18 (11%) have had treatment-related adverse events classified as serious, and there have been no adverse event-related deaths on study.
The high activity of ibrutinib plus venetoclax in CAPTIVATE supports further study of the combination, Dr. Wierda said. A randomized, open-label phase 3 trial of ibrutinib plus venetoclax versus chlorambucil plus obinutuzumab as first-line treatment for CLL is currently recruiting.
The study was sponsored by Pharmacyclics, an AbbVie company. Dr. Wierda reported consulting and research funding from Pharmacyclics, AbbVie, and several other companies.
SOURCE: Wierda WG et al. ASCO 2018, Abstract 7502.
CHICAGO – The combination of ibrutinib plus venetoclax yielded a high rate of undetectable minimal residual disease (MRD) when used as first-line treatment for chronic lymphocytic leukemia (CLL), according to preliminary results of the CAPTIVATE trial.
Of the first 30 patients in the trial, 23 (77%) had undetectable blood MRD after just six cycles of combined treatment, said investigator William G. Wierda, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston.
“These early results show a highly active and safe treatment with 12 cycles of combined treatment with ibrutinib and venetoclax,” Dr. Wierda said in a presentation of the CAPTIVATE results at the annual meeting of the American Society of Clinical Oncology.
Those MRD results are “at least as good as we can achieve with chemoimmunotherapy,” Bruce D. Cheson, MD, head of hematology at Georgetown University, Washington, said during a discussion of the CAPTIVATE study results.
Dr. Cheson referenced MRD results from a 2016 analysis of the CLL8 and CLL10 trials, which included patients treated with fludarabine, cyclophosphamide, and rituximab (FCR) and bendamustine plus rituximab (BR). In that analysis, 33.6% of patients achieved MRD-negative complete response and 29.1% achieved MRD-negative partial response.
In CAPTIVATE, by contrast, all of the complete remissions were MRD negative, as were a majority of the partial responders, Dr. Cheson noted.
Venetoclax and ibrutinib have “clinically complimentary activity” that provided a rationale for combining the two, Dr. Wierda said at ASCO. Ibrutinib is a BTK inhibitor that has a high rate of response and durable disease control, though continuous treatment is indicated, he said, because most patients achieve partial remissions as best response and continue to have residual disease in blood or bone marrow. Venetoclax, he added, is a BCL-2 inhibitor that produces durable partial remissions, though “residual disease is typically present in the form of persistently enlarged lymph nodes,” he said. “Venetoclax is highly effective at clearing disease from blood and bone marrow.”
The phase 2 CAPTIVATE trial includes a total of 164 patients younger than 70 years of age who receive a 3-cycle ibrutinib lead-in, followed by ibrutinib plus venetoclax for 12 cycles. At that point, patients are randomized according to MRD status. Patients with confirmed undetectable MRD are randomized to further treatment with ibrutinib or placebo, and those with undetectable MRD not confirmed are randomized to ibrutinib versus ibrutinib plus venetoclax.
In addition to early efficacy data, Dr. Wierda also reported some safety data. Compared with the single-agent ibrutinib lead-in period, combined ibrutinib plus venetoclax treatment had more gastrointestinal-associated events and neutropenia. Almost half of patients (45%) have had a treatment-related grade 3-4 adverse event, though just 18 (11%) have had treatment-related adverse events classified as serious, and there have been no adverse event-related deaths on study.
The high activity of ibrutinib plus venetoclax in CAPTIVATE supports further study of the combination, Dr. Wierda said. A randomized, open-label phase 3 trial of ibrutinib plus venetoclax versus chlorambucil plus obinutuzumab as first-line treatment for CLL is currently recruiting.
The study was sponsored by Pharmacyclics, an AbbVie company. Dr. Wierda reported consulting and research funding from Pharmacyclics, AbbVie, and several other companies.
SOURCE: Wierda WG et al. ASCO 2018, Abstract 7502.
REPORTING FROM ASCO 2018
Key clinical point:
Major finding: Of 14 patients, 12 (86%) who completed 12 cycles of treatment had undetectable bone marrow MRD.
Study details: Early results of the phase 2 CAPTIVATE trial including 164 patients younger than 70 years of age with previously untreated CLL.
Disclosures: The study was sponsored by Pharmacyclics, an Abbvie company. Dr. Wierda reported consulting and research funding from Pharmacyclics, AbbVie, and several other companies.
Source: Wierda WG et al. ASCO 2018, Abstract 7502.
Polatuzumab plus BR improves efficacy in DLBCL
CHICAGO—Polatuzumab vedotin, when added to bendamustine (B) and rituximab (R), significantly improved response and survival rates in a cohort of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to a phase 2 study.
By contrast, there were no such improvements in a cohort of follicular lymphoma (FL) patients, at least in short-term follow-up, investigator Laurie Helen Sehn, MD, of the BC Cancer Agency in Vancouver, Canada, said at the 2018 ASCO Annual Meeting.
However, the improvement in overall survival in DLBCL patients is “remarkable,” Dr Sehn affirmed in an oral presentation (abstract 7507).
“Based on these encouraging results, polatuzumab vedotin has received breakthrough therapy designation and priority medicines designation by the FDA and EMA for patients with relapsed or refractory DLBCL,” she said.
Polatuzumab-BR study (NCT02257567)
The study by Dr Sehn and colleagues included a cohort of 80 DLBCL patients randomized to BR or polatuzumab-BR for 6 planned 21-day cycles.
Investigators randomized another cohort of 80 FL patients to BR or polatuzumab-BR for 6 planned 28-day cycles.
The primary endpoint was complete response (CR) assessed by fluorodeoxyglucose positron emission tomography (FDG-PET) at 6 to 8 weeks after the end of treatment.
DLBCL patients
A total of 40% of polatuzumab-BR-treated DLBCL patients achieved CR at the end of treatment, versus 15% of BR-treated patients (P=0.012).
That CR improvement translated into a significantly higher progression-free survival (PFS) (6.7 months for polatuzumab-BR vs 2.0 months for BR, P<0.0001) and overall survival (11.8 months versus 4.7 months, P=0.0008), according to Dr Sehn.
The FDG-PET CR rates were higher in the polatuzumab-BR arm regardless of the number of prior lines of treatment for DLBCL, and regardless of relapsed versus refractory status, Dr. Sehn added.
FL patients
By contrast, in the FL cohort, the FDG-PET CR rate was high for both arms, at 69% for polatuzumab-BR and 63% for BR.
And there was no significant difference in progression-free survival (P=0.58) with “relatively short-term follow-up,” she said.
Adverse events
The most common grades 3 – 5 adverse events for both DLBCL and FL patients were higher in the polatuzumab-BR arm than the BR arm and included cytopenias, febrile neutropenia, and infections.
Serious AEs were also higher in the polatuzumab-BR arm and included febrile neutropenia for both FL and DLBCL patients and infection for FL patients.
Five percent of FL patients and 18% of DLBCL had a grade 5 event.
Commentary
Whether polatuzumab vedotin will change treatment paradigms for DLBCL patients may be answered by the ongoing POLARIX study, according to Alison Moskowitz, MD, of Memorial Sloan Kettering Cancer Center in New York, NY.
The randomized phase 3 POLARIX study (abstract TPS7589) is comparing polatuzumab plus R-CHP to R-CHOP in patients with previously untreated DLBCL.
“Certainly, there are patients who do very well with R-CHOP chemotherapy alone, and so we need to learn whether this is necessary for all patients, or only the high-risk patients,” Dr Moskowitz said in a talk at ASCO commenting on the results of the polatuzumab-BR study.
Hoffman-LaRoche is the sponsor of the study.
CHICAGO—Polatuzumab vedotin, when added to bendamustine (B) and rituximab (R), significantly improved response and survival rates in a cohort of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to a phase 2 study.
By contrast, there were no such improvements in a cohort of follicular lymphoma (FL) patients, at least in short-term follow-up, investigator Laurie Helen Sehn, MD, of the BC Cancer Agency in Vancouver, Canada, said at the 2018 ASCO Annual Meeting.
However, the improvement in overall survival in DLBCL patients is “remarkable,” Dr Sehn affirmed in an oral presentation (abstract 7507).
“Based on these encouraging results, polatuzumab vedotin has received breakthrough therapy designation and priority medicines designation by the FDA and EMA for patients with relapsed or refractory DLBCL,” she said.
Polatuzumab-BR study (NCT02257567)
The study by Dr Sehn and colleagues included a cohort of 80 DLBCL patients randomized to BR or polatuzumab-BR for 6 planned 21-day cycles.
Investigators randomized another cohort of 80 FL patients to BR or polatuzumab-BR for 6 planned 28-day cycles.
The primary endpoint was complete response (CR) assessed by fluorodeoxyglucose positron emission tomography (FDG-PET) at 6 to 8 weeks after the end of treatment.
DLBCL patients
A total of 40% of polatuzumab-BR-treated DLBCL patients achieved CR at the end of treatment, versus 15% of BR-treated patients (P=0.012).
That CR improvement translated into a significantly higher progression-free survival (PFS) (6.7 months for polatuzumab-BR vs 2.0 months for BR, P<0.0001) and overall survival (11.8 months versus 4.7 months, P=0.0008), according to Dr Sehn.
The FDG-PET CR rates were higher in the polatuzumab-BR arm regardless of the number of prior lines of treatment for DLBCL, and regardless of relapsed versus refractory status, Dr. Sehn added.
FL patients
By contrast, in the FL cohort, the FDG-PET CR rate was high for both arms, at 69% for polatuzumab-BR and 63% for BR.
And there was no significant difference in progression-free survival (P=0.58) with “relatively short-term follow-up,” she said.
Adverse events
The most common grades 3 – 5 adverse events for both DLBCL and FL patients were higher in the polatuzumab-BR arm than the BR arm and included cytopenias, febrile neutropenia, and infections.
Serious AEs were also higher in the polatuzumab-BR arm and included febrile neutropenia for both FL and DLBCL patients and infection for FL patients.
Five percent of FL patients and 18% of DLBCL had a grade 5 event.
Commentary
Whether polatuzumab vedotin will change treatment paradigms for DLBCL patients may be answered by the ongoing POLARIX study, according to Alison Moskowitz, MD, of Memorial Sloan Kettering Cancer Center in New York, NY.
The randomized phase 3 POLARIX study (abstract TPS7589) is comparing polatuzumab plus R-CHP to R-CHOP in patients with previously untreated DLBCL.
“Certainly, there are patients who do very well with R-CHOP chemotherapy alone, and so we need to learn whether this is necessary for all patients, or only the high-risk patients,” Dr Moskowitz said in a talk at ASCO commenting on the results of the polatuzumab-BR study.
Hoffman-LaRoche is the sponsor of the study.
CHICAGO—Polatuzumab vedotin, when added to bendamustine (B) and rituximab (R), significantly improved response and survival rates in a cohort of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to a phase 2 study.
By contrast, there were no such improvements in a cohort of follicular lymphoma (FL) patients, at least in short-term follow-up, investigator Laurie Helen Sehn, MD, of the BC Cancer Agency in Vancouver, Canada, said at the 2018 ASCO Annual Meeting.
However, the improvement in overall survival in DLBCL patients is “remarkable,” Dr Sehn affirmed in an oral presentation (abstract 7507).
“Based on these encouraging results, polatuzumab vedotin has received breakthrough therapy designation and priority medicines designation by the FDA and EMA for patients with relapsed or refractory DLBCL,” she said.
Polatuzumab-BR study (NCT02257567)
The study by Dr Sehn and colleagues included a cohort of 80 DLBCL patients randomized to BR or polatuzumab-BR for 6 planned 21-day cycles.
Investigators randomized another cohort of 80 FL patients to BR or polatuzumab-BR for 6 planned 28-day cycles.
The primary endpoint was complete response (CR) assessed by fluorodeoxyglucose positron emission tomography (FDG-PET) at 6 to 8 weeks after the end of treatment.
DLBCL patients
A total of 40% of polatuzumab-BR-treated DLBCL patients achieved CR at the end of treatment, versus 15% of BR-treated patients (P=0.012).
That CR improvement translated into a significantly higher progression-free survival (PFS) (6.7 months for polatuzumab-BR vs 2.0 months for BR, P<0.0001) and overall survival (11.8 months versus 4.7 months, P=0.0008), according to Dr Sehn.
The FDG-PET CR rates were higher in the polatuzumab-BR arm regardless of the number of prior lines of treatment for DLBCL, and regardless of relapsed versus refractory status, Dr. Sehn added.
FL patients
By contrast, in the FL cohort, the FDG-PET CR rate was high for both arms, at 69% for polatuzumab-BR and 63% for BR.
And there was no significant difference in progression-free survival (P=0.58) with “relatively short-term follow-up,” she said.
Adverse events
The most common grades 3 – 5 adverse events for both DLBCL and FL patients were higher in the polatuzumab-BR arm than the BR arm and included cytopenias, febrile neutropenia, and infections.
Serious AEs were also higher in the polatuzumab-BR arm and included febrile neutropenia for both FL and DLBCL patients and infection for FL patients.
Five percent of FL patients and 18% of DLBCL had a grade 5 event.
Commentary
Whether polatuzumab vedotin will change treatment paradigms for DLBCL patients may be answered by the ongoing POLARIX study, according to Alison Moskowitz, MD, of Memorial Sloan Kettering Cancer Center in New York, NY.
The randomized phase 3 POLARIX study (abstract TPS7589) is comparing polatuzumab plus R-CHP to R-CHOP in patients with previously untreated DLBCL.
“Certainly, there are patients who do very well with R-CHOP chemotherapy alone, and so we need to learn whether this is necessary for all patients, or only the high-risk patients,” Dr Moskowitz said in a talk at ASCO commenting on the results of the polatuzumab-BR study.
Hoffman-LaRoche is the sponsor of the study.
Chemo-free regimen appears viable in previously untreated FL
CHICAGO – Lenalidomide plus rituximab (R2) had comparable efficacy versus standard chemoimmunotherapy in patients with previously untreated follicular lymphoma, according to results from a phase 3 trial.
RELEVANCE is the first randomized, phase 3 trial to examine a chemotherapy-free regimen in this setting.
Response and progression-free survival (PFS) results were similar for patients who received R2 followed by rituximab maintenance and patients assigned to chemotherapy plus rituximab and rituximab maintenance, in study results presented at the annual meeting of the American Society of Clinical Oncology.
“These results show that lenalidomide plus rituximab, which is a novel immunomodulatory approach, is a potential first-line option for patients with follicular lymphoma that require treatment,” said investigator Nathan H. Fowler, MD, of the University of Texas MD Anderson Cancer Center, Houston.
But since the study was designed as a superiority trial, rather than a noninferiority trial, and it failed to meet its primary endpoint of superior complete remission (CR) or CR unconfirmed (CRu) at 120 weeks, said Bruce D. Cheson, MD, head of hematology at Georgetown University, Washington.
R2 had a similar PFS overall and in all major patient subgroups, similar overall survival, less nonhematologic toxicity aside from rash, less neutropenia, and fewer infections despite increased use of growth factors in the chemoimmunotherapy arm, Dr. Cheson said in a presentation commenting on the results. “Therefore, I agree with Dr. Fowler’s conclusion that R2 can be considered as an option for the front-line therapy of patients with follicular lymphoma,” Dr. Cheson said.
The RELEVANCE study included 1,030 patients (median age, 59 years) with previously untreated, advanced follicular lymphoma requiring treatment. They were randomized 1:1 to either lenalidomide plus rituximab followed by rituximab maintenance, or R-chemotherapy followed by rituximab maintenance.
For patients randomly assigned to R-chemotherapy, physicians could choose among three standard regimens: rituximab plus bendamustine (R-B), rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), or rituximab plus cyclophosphamide, vincristine, and prednisone (R-CVP).
There was no statistical difference between treatment approaches in CR/CRu at 120 weeks, which was 48% in the R2 arm and 53% in the R-chemotherapy arm (P = 0.13). Best CR/CRu also was not statistically different between arms (59% and 67%, respectively), as was best overall response rate (84% and 89%). The 3-year duration of response was 77% in the R2 arm and 74% for R-chemotherapy.
With 37.9 months median follow-up, progression-free survival was “nearly identical” between the two groups, Dr. Fowler said, at 77% for R2 and 78% for R-chemotherapy (P = 0.48). The 3-year overall survival was 94% in both the R2 and R-chemotherapy arms, though survival data are still immature, Dr. Fowler noted.
Grade 3/4 neutropenia was more common in the R-chemotherapy arm, resulting in higher rates of febrile neutropenia, according to Dr. Fowler, who also noted that rash and cutaneous reactions were more common with R2. About 70% of patients in each arm were able to tolerate treatment, and reasons for discontinuation were “fairly similar” between arms, Dr. Fowler added.
Second primary malignancies occurred in 7% of patients in the R2 arm and 10% of the R-chemotherapy arm.
The study was sponsored was Celgene and the Lymphoma Academic Research Organisation. Dr. Fowler reported disclosures related to Abbvie, Celgene, Janssen, Merck, and Roche.
SOURCE: Fowler NH et al. ASCO 2018, Abstract 7500.
CHICAGO – Lenalidomide plus rituximab (R2) had comparable efficacy versus standard chemoimmunotherapy in patients with previously untreated follicular lymphoma, according to results from a phase 3 trial.
RELEVANCE is the first randomized, phase 3 trial to examine a chemotherapy-free regimen in this setting.
Response and progression-free survival (PFS) results were similar for patients who received R2 followed by rituximab maintenance and patients assigned to chemotherapy plus rituximab and rituximab maintenance, in study results presented at the annual meeting of the American Society of Clinical Oncology.
“These results show that lenalidomide plus rituximab, which is a novel immunomodulatory approach, is a potential first-line option for patients with follicular lymphoma that require treatment,” said investigator Nathan H. Fowler, MD, of the University of Texas MD Anderson Cancer Center, Houston.
But since the study was designed as a superiority trial, rather than a noninferiority trial, and it failed to meet its primary endpoint of superior complete remission (CR) or CR unconfirmed (CRu) at 120 weeks, said Bruce D. Cheson, MD, head of hematology at Georgetown University, Washington.
R2 had a similar PFS overall and in all major patient subgroups, similar overall survival, less nonhematologic toxicity aside from rash, less neutropenia, and fewer infections despite increased use of growth factors in the chemoimmunotherapy arm, Dr. Cheson said in a presentation commenting on the results. “Therefore, I agree with Dr. Fowler’s conclusion that R2 can be considered as an option for the front-line therapy of patients with follicular lymphoma,” Dr. Cheson said.
The RELEVANCE study included 1,030 patients (median age, 59 years) with previously untreated, advanced follicular lymphoma requiring treatment. They were randomized 1:1 to either lenalidomide plus rituximab followed by rituximab maintenance, or R-chemotherapy followed by rituximab maintenance.
For patients randomly assigned to R-chemotherapy, physicians could choose among three standard regimens: rituximab plus bendamustine (R-B), rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), or rituximab plus cyclophosphamide, vincristine, and prednisone (R-CVP).
There was no statistical difference between treatment approaches in CR/CRu at 120 weeks, which was 48% in the R2 arm and 53% in the R-chemotherapy arm (P = 0.13). Best CR/CRu also was not statistically different between arms (59% and 67%, respectively), as was best overall response rate (84% and 89%). The 3-year duration of response was 77% in the R2 arm and 74% for R-chemotherapy.
With 37.9 months median follow-up, progression-free survival was “nearly identical” between the two groups, Dr. Fowler said, at 77% for R2 and 78% for R-chemotherapy (P = 0.48). The 3-year overall survival was 94% in both the R2 and R-chemotherapy arms, though survival data are still immature, Dr. Fowler noted.
Grade 3/4 neutropenia was more common in the R-chemotherapy arm, resulting in higher rates of febrile neutropenia, according to Dr. Fowler, who also noted that rash and cutaneous reactions were more common with R2. About 70% of patients in each arm were able to tolerate treatment, and reasons for discontinuation were “fairly similar” between arms, Dr. Fowler added.
Second primary malignancies occurred in 7% of patients in the R2 arm and 10% of the R-chemotherapy arm.
The study was sponsored was Celgene and the Lymphoma Academic Research Organisation. Dr. Fowler reported disclosures related to Abbvie, Celgene, Janssen, Merck, and Roche.
SOURCE: Fowler NH et al. ASCO 2018, Abstract 7500.
CHICAGO – Lenalidomide plus rituximab (R2) had comparable efficacy versus standard chemoimmunotherapy in patients with previously untreated follicular lymphoma, according to results from a phase 3 trial.
RELEVANCE is the first randomized, phase 3 trial to examine a chemotherapy-free regimen in this setting.
Response and progression-free survival (PFS) results were similar for patients who received R2 followed by rituximab maintenance and patients assigned to chemotherapy plus rituximab and rituximab maintenance, in study results presented at the annual meeting of the American Society of Clinical Oncology.
“These results show that lenalidomide plus rituximab, which is a novel immunomodulatory approach, is a potential first-line option for patients with follicular lymphoma that require treatment,” said investigator Nathan H. Fowler, MD, of the University of Texas MD Anderson Cancer Center, Houston.
But since the study was designed as a superiority trial, rather than a noninferiority trial, and it failed to meet its primary endpoint of superior complete remission (CR) or CR unconfirmed (CRu) at 120 weeks, said Bruce D. Cheson, MD, head of hematology at Georgetown University, Washington.
R2 had a similar PFS overall and in all major patient subgroups, similar overall survival, less nonhematologic toxicity aside from rash, less neutropenia, and fewer infections despite increased use of growth factors in the chemoimmunotherapy arm, Dr. Cheson said in a presentation commenting on the results. “Therefore, I agree with Dr. Fowler’s conclusion that R2 can be considered as an option for the front-line therapy of patients with follicular lymphoma,” Dr. Cheson said.
The RELEVANCE study included 1,030 patients (median age, 59 years) with previously untreated, advanced follicular lymphoma requiring treatment. They were randomized 1:1 to either lenalidomide plus rituximab followed by rituximab maintenance, or R-chemotherapy followed by rituximab maintenance.
For patients randomly assigned to R-chemotherapy, physicians could choose among three standard regimens: rituximab plus bendamustine (R-B), rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), or rituximab plus cyclophosphamide, vincristine, and prednisone (R-CVP).
There was no statistical difference between treatment approaches in CR/CRu at 120 weeks, which was 48% in the R2 arm and 53% in the R-chemotherapy arm (P = 0.13). Best CR/CRu also was not statistically different between arms (59% and 67%, respectively), as was best overall response rate (84% and 89%). The 3-year duration of response was 77% in the R2 arm and 74% for R-chemotherapy.
With 37.9 months median follow-up, progression-free survival was “nearly identical” between the two groups, Dr. Fowler said, at 77% for R2 and 78% for R-chemotherapy (P = 0.48). The 3-year overall survival was 94% in both the R2 and R-chemotherapy arms, though survival data are still immature, Dr. Fowler noted.
Grade 3/4 neutropenia was more common in the R-chemotherapy arm, resulting in higher rates of febrile neutropenia, according to Dr. Fowler, who also noted that rash and cutaneous reactions were more common with R2. About 70% of patients in each arm were able to tolerate treatment, and reasons for discontinuation were “fairly similar” between arms, Dr. Fowler added.
Second primary malignancies occurred in 7% of patients in the R2 arm and 10% of the R-chemotherapy arm.
The study was sponsored was Celgene and the Lymphoma Academic Research Organisation. Dr. Fowler reported disclosures related to Abbvie, Celgene, Janssen, Merck, and Roche.
SOURCE: Fowler NH et al. ASCO 2018, Abstract 7500.
REPORTING FROM ASCO 2018
Key clinical point: in patients with previously untreated follicular lymphoma.
Major finding: With 37.9 months’ median follow-up, progression-free survival was “nearly identical” between the two groups, at 77% for R2 and 78% for rituximab chemotherapy (P = 0.48).
Study details: RELEVANCE, a phase 3, randomized clinical trial including 1,030 patients with previously untreated, advanced follicular lymphoma requiring treatment.
Disclosures: The study was sponsored was Celgene and the Lymphoma Academic Research Organisation. Dr. Fowler reported disclosures related to AbbVie, Celgene, Janssen, Merck, and Roche.
Source: Fowler NH et al. ASCO 2018, Abstract 7500.
Novel antibody shifts ‘eat me/don’t eat me’ balance in refractory NHL
CHICAGO – A first-in-class antibody targeting the macrophage checkpoint CD47 is a promising novel immunotherapy in non-Hodgkin lymphoma, according to Ranjana H. Advani, MD, of Stanford (Calif.) Cancer Institute.
Treatment with Hu5F9-G4 (5F9), an antibody designed to overcome the “don’t eat me” signal associated with CD47, produced “encouraging” antitumor activity in a phase 1b study of 22 patients, Dr. Advani said in an oral abstract presentation at the annual meeting of the American Society of Clinical Oncology.
“5F9 was well tolerated in combination with rituximab, with no maximum tolerated dose achieved,” said Dr. Advani, noting that there were complete remissions in 43% of the refractory follicular lymphoma patients and 33% of refractory diffuse large B-cell lymphoma patients in the phase 1b/2 study.
The antibody has an on-target anemia effect that occurs upon administration, but that was mitigated considerably by a priming and maintenance dosing approach, she added.
The study has demonstrated “excellent” response rates in a highly refractory patient population, said Caron A. Jacobson, MD, of Dana-Farber Cancer Institute and Harvard Medical School in Boston. “Targeting CD47 ... really helps to shift the balance from ‘don’t eat me’ to ‘eat me,’ ” Dr. Jacobson said at the meeting.
“Importantly, we saw very little toxicity in the study, with very few grade 4 adverse events and no immune-related adverse events,” she added.
Most adverse events were grade 1 or 2, with the most common being the expected on-target anemia associated with 5F9. Using an initial priming dose of 5F9 results in a “temporary and mild decline” in hemoglobin due to clearance of aged red blood cells, Dr. Advani said.
The objective response rate in the study was 50%, with efficacy observed in rituximab-refractory patients, Dr. Advani said. With a median follow-up of greater than 6 months, just 1 of 11 responders had progressed. The median duration of response was not reached, with the longest complete remission lasting more than 14 months.
5F9 is able to selectively eliminate cancer cells through blockade of CD47, while rituximab enhances 5F9’s activity via antibody-dependent cellular phagocytosis, according to Dr. Advani.
“CD47 blockade takes the foot off the brakes, while rituximab puts the foot on the accelerator, leading to maximal tumor phagocytosis,” she said.
The Food and Drug Administration recently granted 5F9 a fast track designation for both diffuse large B-cell lymphoma and follicular lymphoma. Phase 2 investigations of 5F9 in these lymphomas are ongoing, Dr. Advani said.
The trial is sponsored by Forty Seven. Dr. Advani reported research funding from Forty Seven, which is developing 5F9, as well as disclosures related to AstraZeneca, Bayer, Bristol-Myers Squibb, Cell Medica, Genentech/Roche, Gilead Sciences, Pharmacyclics, and Seattle Genetics, among others.
SOURCE: Advani RH et al. ASCO 2018, abstract 7504.
CHICAGO – A first-in-class antibody targeting the macrophage checkpoint CD47 is a promising novel immunotherapy in non-Hodgkin lymphoma, according to Ranjana H. Advani, MD, of Stanford (Calif.) Cancer Institute.
Treatment with Hu5F9-G4 (5F9), an antibody designed to overcome the “don’t eat me” signal associated with CD47, produced “encouraging” antitumor activity in a phase 1b study of 22 patients, Dr. Advani said in an oral abstract presentation at the annual meeting of the American Society of Clinical Oncology.
“5F9 was well tolerated in combination with rituximab, with no maximum tolerated dose achieved,” said Dr. Advani, noting that there were complete remissions in 43% of the refractory follicular lymphoma patients and 33% of refractory diffuse large B-cell lymphoma patients in the phase 1b/2 study.
The antibody has an on-target anemia effect that occurs upon administration, but that was mitigated considerably by a priming and maintenance dosing approach, she added.
The study has demonstrated “excellent” response rates in a highly refractory patient population, said Caron A. Jacobson, MD, of Dana-Farber Cancer Institute and Harvard Medical School in Boston. “Targeting CD47 ... really helps to shift the balance from ‘don’t eat me’ to ‘eat me,’ ” Dr. Jacobson said at the meeting.
“Importantly, we saw very little toxicity in the study, with very few grade 4 adverse events and no immune-related adverse events,” she added.
Most adverse events were grade 1 or 2, with the most common being the expected on-target anemia associated with 5F9. Using an initial priming dose of 5F9 results in a “temporary and mild decline” in hemoglobin due to clearance of aged red blood cells, Dr. Advani said.
The objective response rate in the study was 50%, with efficacy observed in rituximab-refractory patients, Dr. Advani said. With a median follow-up of greater than 6 months, just 1 of 11 responders had progressed. The median duration of response was not reached, with the longest complete remission lasting more than 14 months.
5F9 is able to selectively eliminate cancer cells through blockade of CD47, while rituximab enhances 5F9’s activity via antibody-dependent cellular phagocytosis, according to Dr. Advani.
“CD47 blockade takes the foot off the brakes, while rituximab puts the foot on the accelerator, leading to maximal tumor phagocytosis,” she said.
The Food and Drug Administration recently granted 5F9 a fast track designation for both diffuse large B-cell lymphoma and follicular lymphoma. Phase 2 investigations of 5F9 in these lymphomas are ongoing, Dr. Advani said.
The trial is sponsored by Forty Seven. Dr. Advani reported research funding from Forty Seven, which is developing 5F9, as well as disclosures related to AstraZeneca, Bayer, Bristol-Myers Squibb, Cell Medica, Genentech/Roche, Gilead Sciences, Pharmacyclics, and Seattle Genetics, among others.
SOURCE: Advani RH et al. ASCO 2018, abstract 7504.
CHICAGO – A first-in-class antibody targeting the macrophage checkpoint CD47 is a promising novel immunotherapy in non-Hodgkin lymphoma, according to Ranjana H. Advani, MD, of Stanford (Calif.) Cancer Institute.
Treatment with Hu5F9-G4 (5F9), an antibody designed to overcome the “don’t eat me” signal associated with CD47, produced “encouraging” antitumor activity in a phase 1b study of 22 patients, Dr. Advani said in an oral abstract presentation at the annual meeting of the American Society of Clinical Oncology.
“5F9 was well tolerated in combination with rituximab, with no maximum tolerated dose achieved,” said Dr. Advani, noting that there were complete remissions in 43% of the refractory follicular lymphoma patients and 33% of refractory diffuse large B-cell lymphoma patients in the phase 1b/2 study.
The antibody has an on-target anemia effect that occurs upon administration, but that was mitigated considerably by a priming and maintenance dosing approach, she added.
The study has demonstrated “excellent” response rates in a highly refractory patient population, said Caron A. Jacobson, MD, of Dana-Farber Cancer Institute and Harvard Medical School in Boston. “Targeting CD47 ... really helps to shift the balance from ‘don’t eat me’ to ‘eat me,’ ” Dr. Jacobson said at the meeting.
“Importantly, we saw very little toxicity in the study, with very few grade 4 adverse events and no immune-related adverse events,” she added.
Most adverse events were grade 1 or 2, with the most common being the expected on-target anemia associated with 5F9. Using an initial priming dose of 5F9 results in a “temporary and mild decline” in hemoglobin due to clearance of aged red blood cells, Dr. Advani said.
The objective response rate in the study was 50%, with efficacy observed in rituximab-refractory patients, Dr. Advani said. With a median follow-up of greater than 6 months, just 1 of 11 responders had progressed. The median duration of response was not reached, with the longest complete remission lasting more than 14 months.
5F9 is able to selectively eliminate cancer cells through blockade of CD47, while rituximab enhances 5F9’s activity via antibody-dependent cellular phagocytosis, according to Dr. Advani.
“CD47 blockade takes the foot off the brakes, while rituximab puts the foot on the accelerator, leading to maximal tumor phagocytosis,” she said.
The Food and Drug Administration recently granted 5F9 a fast track designation for both diffuse large B-cell lymphoma and follicular lymphoma. Phase 2 investigations of 5F9 in these lymphomas are ongoing, Dr. Advani said.
The trial is sponsored by Forty Seven. Dr. Advani reported research funding from Forty Seven, which is developing 5F9, as well as disclosures related to AstraZeneca, Bayer, Bristol-Myers Squibb, Cell Medica, Genentech/Roche, Gilead Sciences, Pharmacyclics, and Seattle Genetics, among others.
SOURCE: Advani RH et al. ASCO 2018, abstract 7504.
REPORTING FROM ASCO 2018
Key clinical point:
Major finding: Complete responses were seen in 43% of follicular lymphoma (FL) patients and 33% of diffuse large B-cell lymphoma (DLBCL) patients.
Study details: Initial reported results from a phase 1b/2 study of 7 patients with FL and 15 patients with DLBCL.
Disclosures: Forty Seven sponsored the trial. Dr. Advani reported research funding from Forty Seven, which is developing 5F9, as well as disclosures related to AstraZeneca, Bayer, Bristol-Myers Squibb, Cell Medica, Genentech/Roche, Gilead Sciences, Pharmacyclics, and Seattle Genetics, among others.
Source: Advani RH et al. ASCO 2018, abstract 7504.
Single-agent acalabrutinib ‘impressive’ in patients with WM
CHICAGO—Acalabrutinib monotherapy was highly effective in Waldenström’s macroglobulinemia (WM) in a phase 2 study, investigator Roger Owen, MD, reported at the 2018 ASCO Annual Meeting.
The BTK inhibitor was effective in both treatment-naïve and relapsed/refractory patients, with overall response rates for both groups in excess of 90%, and “amazing” major response rates—partial response or better—of approximately 80%, Dr Owen said.
Dr Owen, of the St James's Institute of Oncology, Leeds Teaching Hospitals NHS Trust in Leeds, UK, reported the findings as abstract 7501.*
Durations of response were excellent, according to Dr Owen, who also reported 2-year progression-free survival of 90% in treatment-naïve patients and 82% in relapsed/refractory patients.
The safety profile was favorable, with most adverse events of low grade, and a very limited number of dropouts due to adverse events, according to the investigator.
“I think this study clearly demonstrates the highly effective nature of acalabrutinib in Waldenström’s macroglobulinemia,” Dr Owen stated.
Acalabrutinib is a selective BTK inhibitor with minimal off-target activity, he said. The BTK inhibitor ibrutinib also has demonstrated activity in Waldenström’s, but has been associated with toxicities such as atrial fibrillation and bleeding, he noted.
In this phase 2 acalabrutinib study (NCT02180724), which included 14 treatment-naïve and 92 relapsed/refractory patients, atrial fibrillation occurred in 5 patients. However, 4 of those cases were grade 1-2, and only one was grade 3, according to Dr Owen.
Investigators observed grade 3 hypertension in 3 relapsed/refractory patients.
Bleeding events occurred in more than half of patients, though only 3 of those events were grade 3, and no patient discontinued treatment due to a bleeding episode.
These efficacy results are “impressive,” and the fact that very few cardiac events were seen is important, said Bruce D. Cheson, MD, of Georgetown University Medical Center in Washington, DC.
Dr Cheson commented on the acalabrutinib results in his presentation during ASCO on non-chemotherapy treatments for lymphoid malignancies.
“One can construct a non-chemo algorithm now for Waldenström’s, for patients who are MYD88 mutated, which is more than 90% of patients,” he said. “Right now ibrutinib, and perhaps in the future acalabrutinib, can be the initial therapy with or without rituximab based on the results of ongoing trials.”
However, single non-chemotherapy agents will not be sufficient to achieve cure of lymphoid malignancies, Dr Cheson added.
“We need to carefully develop rational combinations, identifying biomarkers for response, for resistance, for toxicity,” he said.
The study was sponsored by Acerta Pharma BV.
*Data presented at the meeting differ from the abstract.
CHICAGO—Acalabrutinib monotherapy was highly effective in Waldenström’s macroglobulinemia (WM) in a phase 2 study, investigator Roger Owen, MD, reported at the 2018 ASCO Annual Meeting.
The BTK inhibitor was effective in both treatment-naïve and relapsed/refractory patients, with overall response rates for both groups in excess of 90%, and “amazing” major response rates—partial response or better—of approximately 80%, Dr Owen said.
Dr Owen, of the St James's Institute of Oncology, Leeds Teaching Hospitals NHS Trust in Leeds, UK, reported the findings as abstract 7501.*
Durations of response were excellent, according to Dr Owen, who also reported 2-year progression-free survival of 90% in treatment-naïve patients and 82% in relapsed/refractory patients.
The safety profile was favorable, with most adverse events of low grade, and a very limited number of dropouts due to adverse events, according to the investigator.
“I think this study clearly demonstrates the highly effective nature of acalabrutinib in Waldenström’s macroglobulinemia,” Dr Owen stated.
Acalabrutinib is a selective BTK inhibitor with minimal off-target activity, he said. The BTK inhibitor ibrutinib also has demonstrated activity in Waldenström’s, but has been associated with toxicities such as atrial fibrillation and bleeding, he noted.
In this phase 2 acalabrutinib study (NCT02180724), which included 14 treatment-naïve and 92 relapsed/refractory patients, atrial fibrillation occurred in 5 patients. However, 4 of those cases were grade 1-2, and only one was grade 3, according to Dr Owen.
Investigators observed grade 3 hypertension in 3 relapsed/refractory patients.
Bleeding events occurred in more than half of patients, though only 3 of those events were grade 3, and no patient discontinued treatment due to a bleeding episode.
These efficacy results are “impressive,” and the fact that very few cardiac events were seen is important, said Bruce D. Cheson, MD, of Georgetown University Medical Center in Washington, DC.
Dr Cheson commented on the acalabrutinib results in his presentation during ASCO on non-chemotherapy treatments for lymphoid malignancies.
“One can construct a non-chemo algorithm now for Waldenström’s, for patients who are MYD88 mutated, which is more than 90% of patients,” he said. “Right now ibrutinib, and perhaps in the future acalabrutinib, can be the initial therapy with or without rituximab based on the results of ongoing trials.”
However, single non-chemotherapy agents will not be sufficient to achieve cure of lymphoid malignancies, Dr Cheson added.
“We need to carefully develop rational combinations, identifying biomarkers for response, for resistance, for toxicity,” he said.
The study was sponsored by Acerta Pharma BV.
*Data presented at the meeting differ from the abstract.
CHICAGO—Acalabrutinib monotherapy was highly effective in Waldenström’s macroglobulinemia (WM) in a phase 2 study, investigator Roger Owen, MD, reported at the 2018 ASCO Annual Meeting.
The BTK inhibitor was effective in both treatment-naïve and relapsed/refractory patients, with overall response rates for both groups in excess of 90%, and “amazing” major response rates—partial response or better—of approximately 80%, Dr Owen said.
Dr Owen, of the St James's Institute of Oncology, Leeds Teaching Hospitals NHS Trust in Leeds, UK, reported the findings as abstract 7501.*
Durations of response were excellent, according to Dr Owen, who also reported 2-year progression-free survival of 90% in treatment-naïve patients and 82% in relapsed/refractory patients.
The safety profile was favorable, with most adverse events of low grade, and a very limited number of dropouts due to adverse events, according to the investigator.
“I think this study clearly demonstrates the highly effective nature of acalabrutinib in Waldenström’s macroglobulinemia,” Dr Owen stated.
Acalabrutinib is a selective BTK inhibitor with minimal off-target activity, he said. The BTK inhibitor ibrutinib also has demonstrated activity in Waldenström’s, but has been associated with toxicities such as atrial fibrillation and bleeding, he noted.
In this phase 2 acalabrutinib study (NCT02180724), which included 14 treatment-naïve and 92 relapsed/refractory patients, atrial fibrillation occurred in 5 patients. However, 4 of those cases were grade 1-2, and only one was grade 3, according to Dr Owen.
Investigators observed grade 3 hypertension in 3 relapsed/refractory patients.
Bleeding events occurred in more than half of patients, though only 3 of those events were grade 3, and no patient discontinued treatment due to a bleeding episode.
These efficacy results are “impressive,” and the fact that very few cardiac events were seen is important, said Bruce D. Cheson, MD, of Georgetown University Medical Center in Washington, DC.
Dr Cheson commented on the acalabrutinib results in his presentation during ASCO on non-chemotherapy treatments for lymphoid malignancies.
“One can construct a non-chemo algorithm now for Waldenström’s, for patients who are MYD88 mutated, which is more than 90% of patients,” he said. “Right now ibrutinib, and perhaps in the future acalabrutinib, can be the initial therapy with or without rituximab based on the results of ongoing trials.”
However, single non-chemotherapy agents will not be sufficient to achieve cure of lymphoid malignancies, Dr Cheson added.
“We need to carefully develop rational combinations, identifying biomarkers for response, for resistance, for toxicity,” he said.
The study was sponsored by Acerta Pharma BV.
*Data presented at the meeting differ from the abstract.
MRD-negative status signals better outcomes in CAR T–treated ALL
CHICAGO – Minimal residual disease (MRD)–negative complete remission was strongly associated with improved survival outcomes in patients with B-cell acute lymphocytic leukemia (ALL) who received CD19 chimeric antigen receptor (CAR) T cells, results of a retrospective study showed.
Allogeneic hematopoietic stem cell transplant (HSCT) appeared to improve both disease-free and overall survival in those patients who had achieved MRD-negative complete remission, according to results of the study, which were presented at the annual meeting of the American Society of Clinical Oncology.
“Based upon our interaction testing, the potential benefit [of transplant] appears to exist in both good-risk and bad-risk patients as identified through multivariate modeling,” said study investigator Kevin Anthony Hay, MD, of Fred Hutchinson Cancer Research Center, Seattle.
In a comment on the results, Sarah Cooley, MD, noted that the benefits of allogeneic transplant were apparent regardless of whether the patients met criteria for the good-risk subgroup, which was defined by levels of lactate dehydrogenase (LDH) and platelets along with exposure to fludarabine as part of the conditioning regimen.
“I think this suggests that the goal at this point is to get patients to an MRD-negative state and to potentially curative transplant,” said Dr. Cooley, director of investigator-initiated research at Masonic Medical Center at the University of Minnesota, Minneapolis.
The retrospective analysis by Dr. Hay and his colleagues included 53 adults with relapsed or refractory ALL who had bone marrow or extramedullary disease at baseline and had received CD19 CAR T cells at or under the maximum tolerated dose at least 1 year prior to this analysis. Of that group, 45 (85%) achieved MRD-negative complete remission.
Those patients who did achieve MRD-negative complete remission had an improved median disease-free survival at 7.6 months versus 0.8 months (P less than .0001) and improved overall survival at 20.0 months versus 5.0 months (P = 0.014).
Most of the MRD-negative patients who relapsed did so within the first 6 months, an observation that led investigators to consider whether factors exist that could predict better outcomes.
In a multivariate analysis, they found three variables associated with disease free survival: higher LDH prior to lymphodepletion (hazard ratio, 1.39), along with higher platelet count prior to lymphodepletion and incorporation of fludarabine into the regimen, with hazard ratios of 0.65 and 0.34, respectively.
Using those three characteristics, investigators grouped patients as “good risk” if they had normal LDH, platelet count at or above 100 prior to lymphodepletion that included fludarabine. The 24-month disease-free survival for good-risk patients was 78%, and overall survival was 86%.
The role of allogeneic HSCT after ALL patients achieved MRD-negative complete remission with CAR T-cell therapy was one of the “major questions in the field,” Dr. Hay said.
In this analysis, Dr. Hay and colleagues found that patients who underwent transplant in MRD-negative complete remission had a 24-month disease free survival and overall survival of 61% and 72%, respectively, both of which were significantly higher than in patients with MRD-negative complete remission who had no transplant.
The disease-free survival benefit was not specific to the good-risk group, according to Dr. Hay, who said an interaction test demonstrated no significant interaction between risk group and allogeneic HSCT after CAR T-cell infusion (P = 0.53).
“This is a very important finding that should be further [studied] in an appropriately designed clinical trial,” Dr. Hay said during an oral presentation of the study results.
Dr. Hay and several coauthors reported financial disclosures related to Juno Therapeutics. Other disclosures reported by study coauthors included Cell Medica, Celgene, Eureka Therapeutics, Genentech/Roche, Gilead Sciences, Kite Pharma, Novartis, and others.
SOURCE: Hay KA. ASCO 2018, Abstract 7005.
CHICAGO – Minimal residual disease (MRD)–negative complete remission was strongly associated with improved survival outcomes in patients with B-cell acute lymphocytic leukemia (ALL) who received CD19 chimeric antigen receptor (CAR) T cells, results of a retrospective study showed.
Allogeneic hematopoietic stem cell transplant (HSCT) appeared to improve both disease-free and overall survival in those patients who had achieved MRD-negative complete remission, according to results of the study, which were presented at the annual meeting of the American Society of Clinical Oncology.
“Based upon our interaction testing, the potential benefit [of transplant] appears to exist in both good-risk and bad-risk patients as identified through multivariate modeling,” said study investigator Kevin Anthony Hay, MD, of Fred Hutchinson Cancer Research Center, Seattle.
In a comment on the results, Sarah Cooley, MD, noted that the benefits of allogeneic transplant were apparent regardless of whether the patients met criteria for the good-risk subgroup, which was defined by levels of lactate dehydrogenase (LDH) and platelets along with exposure to fludarabine as part of the conditioning regimen.
“I think this suggests that the goal at this point is to get patients to an MRD-negative state and to potentially curative transplant,” said Dr. Cooley, director of investigator-initiated research at Masonic Medical Center at the University of Minnesota, Minneapolis.
The retrospective analysis by Dr. Hay and his colleagues included 53 adults with relapsed or refractory ALL who had bone marrow or extramedullary disease at baseline and had received CD19 CAR T cells at or under the maximum tolerated dose at least 1 year prior to this analysis. Of that group, 45 (85%) achieved MRD-negative complete remission.
Those patients who did achieve MRD-negative complete remission had an improved median disease-free survival at 7.6 months versus 0.8 months (P less than .0001) and improved overall survival at 20.0 months versus 5.0 months (P = 0.014).
Most of the MRD-negative patients who relapsed did so within the first 6 months, an observation that led investigators to consider whether factors exist that could predict better outcomes.
In a multivariate analysis, they found three variables associated with disease free survival: higher LDH prior to lymphodepletion (hazard ratio, 1.39), along with higher platelet count prior to lymphodepletion and incorporation of fludarabine into the regimen, with hazard ratios of 0.65 and 0.34, respectively.
Using those three characteristics, investigators grouped patients as “good risk” if they had normal LDH, platelet count at or above 100 prior to lymphodepletion that included fludarabine. The 24-month disease-free survival for good-risk patients was 78%, and overall survival was 86%.
The role of allogeneic HSCT after ALL patients achieved MRD-negative complete remission with CAR T-cell therapy was one of the “major questions in the field,” Dr. Hay said.
In this analysis, Dr. Hay and colleagues found that patients who underwent transplant in MRD-negative complete remission had a 24-month disease free survival and overall survival of 61% and 72%, respectively, both of which were significantly higher than in patients with MRD-negative complete remission who had no transplant.
The disease-free survival benefit was not specific to the good-risk group, according to Dr. Hay, who said an interaction test demonstrated no significant interaction between risk group and allogeneic HSCT after CAR T-cell infusion (P = 0.53).
“This is a very important finding that should be further [studied] in an appropriately designed clinical trial,” Dr. Hay said during an oral presentation of the study results.
Dr. Hay and several coauthors reported financial disclosures related to Juno Therapeutics. Other disclosures reported by study coauthors included Cell Medica, Celgene, Eureka Therapeutics, Genentech/Roche, Gilead Sciences, Kite Pharma, Novartis, and others.
SOURCE: Hay KA. ASCO 2018, Abstract 7005.
CHICAGO – Minimal residual disease (MRD)–negative complete remission was strongly associated with improved survival outcomes in patients with B-cell acute lymphocytic leukemia (ALL) who received CD19 chimeric antigen receptor (CAR) T cells, results of a retrospective study showed.
Allogeneic hematopoietic stem cell transplant (HSCT) appeared to improve both disease-free and overall survival in those patients who had achieved MRD-negative complete remission, according to results of the study, which were presented at the annual meeting of the American Society of Clinical Oncology.
“Based upon our interaction testing, the potential benefit [of transplant] appears to exist in both good-risk and bad-risk patients as identified through multivariate modeling,” said study investigator Kevin Anthony Hay, MD, of Fred Hutchinson Cancer Research Center, Seattle.
In a comment on the results, Sarah Cooley, MD, noted that the benefits of allogeneic transplant were apparent regardless of whether the patients met criteria for the good-risk subgroup, which was defined by levels of lactate dehydrogenase (LDH) and platelets along with exposure to fludarabine as part of the conditioning regimen.
“I think this suggests that the goal at this point is to get patients to an MRD-negative state and to potentially curative transplant,” said Dr. Cooley, director of investigator-initiated research at Masonic Medical Center at the University of Minnesota, Minneapolis.
The retrospective analysis by Dr. Hay and his colleagues included 53 adults with relapsed or refractory ALL who had bone marrow or extramedullary disease at baseline and had received CD19 CAR T cells at or under the maximum tolerated dose at least 1 year prior to this analysis. Of that group, 45 (85%) achieved MRD-negative complete remission.
Those patients who did achieve MRD-negative complete remission had an improved median disease-free survival at 7.6 months versus 0.8 months (P less than .0001) and improved overall survival at 20.0 months versus 5.0 months (P = 0.014).
Most of the MRD-negative patients who relapsed did so within the first 6 months, an observation that led investigators to consider whether factors exist that could predict better outcomes.
In a multivariate analysis, they found three variables associated with disease free survival: higher LDH prior to lymphodepletion (hazard ratio, 1.39), along with higher platelet count prior to lymphodepletion and incorporation of fludarabine into the regimen, with hazard ratios of 0.65 and 0.34, respectively.
Using those three characteristics, investigators grouped patients as “good risk” if they had normal LDH, platelet count at or above 100 prior to lymphodepletion that included fludarabine. The 24-month disease-free survival for good-risk patients was 78%, and overall survival was 86%.
The role of allogeneic HSCT after ALL patients achieved MRD-negative complete remission with CAR T-cell therapy was one of the “major questions in the field,” Dr. Hay said.
In this analysis, Dr. Hay and colleagues found that patients who underwent transplant in MRD-negative complete remission had a 24-month disease free survival and overall survival of 61% and 72%, respectively, both of which were significantly higher than in patients with MRD-negative complete remission who had no transplant.
The disease-free survival benefit was not specific to the good-risk group, according to Dr. Hay, who said an interaction test demonstrated no significant interaction between risk group and allogeneic HSCT after CAR T-cell infusion (P = 0.53).
“This is a very important finding that should be further [studied] in an appropriately designed clinical trial,” Dr. Hay said during an oral presentation of the study results.
Dr. Hay and several coauthors reported financial disclosures related to Juno Therapeutics. Other disclosures reported by study coauthors included Cell Medica, Celgene, Eureka Therapeutics, Genentech/Roche, Gilead Sciences, Kite Pharma, Novartis, and others.
SOURCE: Hay KA. ASCO 2018, Abstract 7005.
REPORTING FROM ASCO 2018
Key clinical point:
Major finding: Patients who achieved MRD-negative complete remission had an improved median disease-free survival at 7.6 months versus 0.8 months (P less than .0001)
Study details: A retrospective analysis including 53 patients with ALL who had bone marrow or extramedullary disease at baseline and had received CD19 CAR T cells at or under the maximum tolerated dose at least 1 year prior to this analysis.
Disclosures: Researchers reported financial ties to Juno Therapeutics, Cell Medica, Celgene, Eureka Therapeutics, Genentech/Roche, Gilead Sciences, Kite Pharma, Novartis, and others.
Source: Hay KA. ASCO 2018, Abstract 7005.
FDA approves first biosimilar pegfilgrastim
The US Food and Drug Association (FDA) has approved pegfilgrastim-jmdb (Fulphila™) as the first biosimilar to Neulasta®.
The agents reduce the risk of infection or the duration of febrile neutropenia in patients treated with immunosuppressive chemotherapy for non-myeloid hematologic malignancies.
The FDA approved Fulphila based on evidence that included extensive structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamic data, clinical immunogenicity data, and other clinical safety and effectiveness data.
The evidence demonstrated that Fulphila is biosimilar to Amgen’s Neulasta. The FDA, in its announcement, noted that Fulphila has been approved as a biosimilar and not as an interchangeable product.
A biosimilar is a biological product approved based on data showing it is highly similar to a biological product already approved by the FDA, termed the reference product.
A biosimilar has no clinically meaningful differences from the reference product in terms of safety, purity, and effectiveness.
Common side effects of Fulphila include bone pain and pain in extremities.
The FDA cautions that patients with a history of serious allergic reaction to human granulocyte colony-stimulating factors, such as pegfilgrastim or filgrastim products, should not take Fulphila.
Serious side effects from Fulphila include:
- rupture of the spleen
- acute respiratory distress syndrome
- serious allergic reactions including anaphylaxis
- glomerulonephritis
- leukocytosis
- capillary leak syndrome
- potential for tumor growth
Fatal sickle cell crises have also occurred with Fulphila use.
Fulphila is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.
The FDA is planning to release a comprehensive new plan to advance policy efforts that promote biosimilar product development, according to FDA Commissioner Scott Gotlieb, MD.
“We want to make sure that the pathway for developing biosimilar versions of approved biologics is efficient and effective, so that patients benefit from competition to existing biologics once lawful intellectual property has lapsed on these products,” he said in the announcement.
The FDA granted approval of Fulphila to Mylan GmbH. Mylan is co-developing Fulphila with Biocon.
Last fall, the agency had issued a complete response letter saying it could not approve the proposed biosimilar pending an update to the application.
The complete response letter did not raise any questions on the biosimilarity of Fulphila (investigational drug product MYL-1401H), pharmacokinetic/pharmacodynamic data, clinical data, or immunogenicity, however.
Mylan anticipates launching Fulphila in the coming weeks.
The US Food and Drug Association (FDA) has approved pegfilgrastim-jmdb (Fulphila™) as the first biosimilar to Neulasta®.
The agents reduce the risk of infection or the duration of febrile neutropenia in patients treated with immunosuppressive chemotherapy for non-myeloid hematologic malignancies.
The FDA approved Fulphila based on evidence that included extensive structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamic data, clinical immunogenicity data, and other clinical safety and effectiveness data.
The evidence demonstrated that Fulphila is biosimilar to Amgen’s Neulasta. The FDA, in its announcement, noted that Fulphila has been approved as a biosimilar and not as an interchangeable product.
A biosimilar is a biological product approved based on data showing it is highly similar to a biological product already approved by the FDA, termed the reference product.
A biosimilar has no clinically meaningful differences from the reference product in terms of safety, purity, and effectiveness.
Common side effects of Fulphila include bone pain and pain in extremities.
The FDA cautions that patients with a history of serious allergic reaction to human granulocyte colony-stimulating factors, such as pegfilgrastim or filgrastim products, should not take Fulphila.
Serious side effects from Fulphila include:
- rupture of the spleen
- acute respiratory distress syndrome
- serious allergic reactions including anaphylaxis
- glomerulonephritis
- leukocytosis
- capillary leak syndrome
- potential for tumor growth
Fatal sickle cell crises have also occurred with Fulphila use.
Fulphila is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.
The FDA is planning to release a comprehensive new plan to advance policy efforts that promote biosimilar product development, according to FDA Commissioner Scott Gotlieb, MD.
“We want to make sure that the pathway for developing biosimilar versions of approved biologics is efficient and effective, so that patients benefit from competition to existing biologics once lawful intellectual property has lapsed on these products,” he said in the announcement.
The FDA granted approval of Fulphila to Mylan GmbH. Mylan is co-developing Fulphila with Biocon.
Last fall, the agency had issued a complete response letter saying it could not approve the proposed biosimilar pending an update to the application.
The complete response letter did not raise any questions on the biosimilarity of Fulphila (investigational drug product MYL-1401H), pharmacokinetic/pharmacodynamic data, clinical data, or immunogenicity, however.
Mylan anticipates launching Fulphila in the coming weeks.
The US Food and Drug Association (FDA) has approved pegfilgrastim-jmdb (Fulphila™) as the first biosimilar to Neulasta®.
The agents reduce the risk of infection or the duration of febrile neutropenia in patients treated with immunosuppressive chemotherapy for non-myeloid hematologic malignancies.
The FDA approved Fulphila based on evidence that included extensive structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamic data, clinical immunogenicity data, and other clinical safety and effectiveness data.
The evidence demonstrated that Fulphila is biosimilar to Amgen’s Neulasta. The FDA, in its announcement, noted that Fulphila has been approved as a biosimilar and not as an interchangeable product.
A biosimilar is a biological product approved based on data showing it is highly similar to a biological product already approved by the FDA, termed the reference product.
A biosimilar has no clinically meaningful differences from the reference product in terms of safety, purity, and effectiveness.
Common side effects of Fulphila include bone pain and pain in extremities.
The FDA cautions that patients with a history of serious allergic reaction to human granulocyte colony-stimulating factors, such as pegfilgrastim or filgrastim products, should not take Fulphila.
Serious side effects from Fulphila include:
- rupture of the spleen
- acute respiratory distress syndrome
- serious allergic reactions including anaphylaxis
- glomerulonephritis
- leukocytosis
- capillary leak syndrome
- potential for tumor growth
Fatal sickle cell crises have also occurred with Fulphila use.
Fulphila is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.
The FDA is planning to release a comprehensive new plan to advance policy efforts that promote biosimilar product development, according to FDA Commissioner Scott Gotlieb, MD.
“We want to make sure that the pathway for developing biosimilar versions of approved biologics is efficient and effective, so that patients benefit from competition to existing biologics once lawful intellectual property has lapsed on these products,” he said in the announcement.
The FDA granted approval of Fulphila to Mylan GmbH. Mylan is co-developing Fulphila with Biocon.
Last fall, the agency had issued a complete response letter saying it could not approve the proposed biosimilar pending an update to the application.
The complete response letter did not raise any questions on the biosimilarity of Fulphila (investigational drug product MYL-1401H), pharmacokinetic/pharmacodynamic data, clinical data, or immunogenicity, however.
Mylan anticipates launching Fulphila in the coming weeks.
When is denosumab an option in myeloma?
CHICAGO – , G. David Roodman, MD, PhD, reported at the annual meeting of the American Society of Clinical Oncology.
“We use denosumab in patients with compromised renal function,” said Dr. Roodman, director of the Division of Hematology-Oncology at Indiana University, Indianapolis, noting one such scenario. That use of denosumab echoes recently published ASCO guidelines on bone-modifying therapy.
The second scenario for denosumab use is in patients who aren’t tolerating bisphosphonates: “We switch them from zoledronic acid to pamidronate, and they still have terrible acute phase reactions,” Dr. Roodman said.
Dr. Roodman’s comments on use of denosumab were in response to an audience question about when he would use denosumab, given the considerable cost difference between the RANK ligand inhibitor and bisphosphonates.
The recent ASCO guidelines, of which Dr. Roodman is a coauthor, state that denosumab “is more expensive than zoledronic acid or pamidronate and must be considered in treatment decisions.”
Previously, ASCO guidelines recommended use of intravenous bisphosphonates for patients with myeloma and evidence of bone disease. Based on consideration of new evidence, the guideline authors eliminated the requirement for evidence of bone disease and added denosumab as an alternative treatment choice.
The addition of denosumab was based in part on results of a recent randomized phase 3 trial that comprised 1,718 myeloma patients who were treated with either denosumab or zoledronic acid.
The primary endpoint, time to first on-study skeletal-related event, was evaluated after 676 skeletal-related events had accrued on study. The investigators found no difference in time to first event (hazard ratio [HR], 0.98; 95% confidence interval, 0.85-1.14; P = 0.82).
Likewise, the secondary endpoint of overall survival showed no difference between arms (HR, 0.90; 95% CI, 0.70-1.16), though an exploratory analysis did suggest denosumab was superior on the endpoint of progression-free survival (HR, 0.82; 95% CI, 0.68-0.99).
The ASCO guidelines also recommend that clinicians consider less-frequent dosing in patients with responsive or stable disease. That recommendation is based on results of two studies of less-frequent dosing prompted by concerns over the risk of osteonecrosis of the jaw, an uncommon but potentially serious complication associated with bone-modifying agents.
Both studies suggested every-3-months dosing of zoledronic acid could be effective. However, Dr. Roodman noted that both studies had limitations that need to be considered, including small numbers of myeloma patients, limited duration of therapy studied, and a high dropout rate in the case of one study. Due to those limitations, “it’s very difficult to draw conclusions about this today,” Dr. Roodman said.
Dr. Roodman reported that he had a consulting or advisory role with Amgen.
CHICAGO – , G. David Roodman, MD, PhD, reported at the annual meeting of the American Society of Clinical Oncology.
“We use denosumab in patients with compromised renal function,” said Dr. Roodman, director of the Division of Hematology-Oncology at Indiana University, Indianapolis, noting one such scenario. That use of denosumab echoes recently published ASCO guidelines on bone-modifying therapy.
The second scenario for denosumab use is in patients who aren’t tolerating bisphosphonates: “We switch them from zoledronic acid to pamidronate, and they still have terrible acute phase reactions,” Dr. Roodman said.
Dr. Roodman’s comments on use of denosumab were in response to an audience question about when he would use denosumab, given the considerable cost difference between the RANK ligand inhibitor and bisphosphonates.
The recent ASCO guidelines, of which Dr. Roodman is a coauthor, state that denosumab “is more expensive than zoledronic acid or pamidronate and must be considered in treatment decisions.”
Previously, ASCO guidelines recommended use of intravenous bisphosphonates for patients with myeloma and evidence of bone disease. Based on consideration of new evidence, the guideline authors eliminated the requirement for evidence of bone disease and added denosumab as an alternative treatment choice.
The addition of denosumab was based in part on results of a recent randomized phase 3 trial that comprised 1,718 myeloma patients who were treated with either denosumab or zoledronic acid.
The primary endpoint, time to first on-study skeletal-related event, was evaluated after 676 skeletal-related events had accrued on study. The investigators found no difference in time to first event (hazard ratio [HR], 0.98; 95% confidence interval, 0.85-1.14; P = 0.82).
Likewise, the secondary endpoint of overall survival showed no difference between arms (HR, 0.90; 95% CI, 0.70-1.16), though an exploratory analysis did suggest denosumab was superior on the endpoint of progression-free survival (HR, 0.82; 95% CI, 0.68-0.99).
The ASCO guidelines also recommend that clinicians consider less-frequent dosing in patients with responsive or stable disease. That recommendation is based on results of two studies of less-frequent dosing prompted by concerns over the risk of osteonecrosis of the jaw, an uncommon but potentially serious complication associated with bone-modifying agents.
Both studies suggested every-3-months dosing of zoledronic acid could be effective. However, Dr. Roodman noted that both studies had limitations that need to be considered, including small numbers of myeloma patients, limited duration of therapy studied, and a high dropout rate in the case of one study. Due to those limitations, “it’s very difficult to draw conclusions about this today,” Dr. Roodman said.
Dr. Roodman reported that he had a consulting or advisory role with Amgen.
CHICAGO – , G. David Roodman, MD, PhD, reported at the annual meeting of the American Society of Clinical Oncology.
“We use denosumab in patients with compromised renal function,” said Dr. Roodman, director of the Division of Hematology-Oncology at Indiana University, Indianapolis, noting one such scenario. That use of denosumab echoes recently published ASCO guidelines on bone-modifying therapy.
The second scenario for denosumab use is in patients who aren’t tolerating bisphosphonates: “We switch them from zoledronic acid to pamidronate, and they still have terrible acute phase reactions,” Dr. Roodman said.
Dr. Roodman’s comments on use of denosumab were in response to an audience question about when he would use denosumab, given the considerable cost difference between the RANK ligand inhibitor and bisphosphonates.
The recent ASCO guidelines, of which Dr. Roodman is a coauthor, state that denosumab “is more expensive than zoledronic acid or pamidronate and must be considered in treatment decisions.”
Previously, ASCO guidelines recommended use of intravenous bisphosphonates for patients with myeloma and evidence of bone disease. Based on consideration of new evidence, the guideline authors eliminated the requirement for evidence of bone disease and added denosumab as an alternative treatment choice.
The addition of denosumab was based in part on results of a recent randomized phase 3 trial that comprised 1,718 myeloma patients who were treated with either denosumab or zoledronic acid.
The primary endpoint, time to first on-study skeletal-related event, was evaluated after 676 skeletal-related events had accrued on study. The investigators found no difference in time to first event (hazard ratio [HR], 0.98; 95% confidence interval, 0.85-1.14; P = 0.82).
Likewise, the secondary endpoint of overall survival showed no difference between arms (HR, 0.90; 95% CI, 0.70-1.16), though an exploratory analysis did suggest denosumab was superior on the endpoint of progression-free survival (HR, 0.82; 95% CI, 0.68-0.99).
The ASCO guidelines also recommend that clinicians consider less-frequent dosing in patients with responsive or stable disease. That recommendation is based on results of two studies of less-frequent dosing prompted by concerns over the risk of osteonecrosis of the jaw, an uncommon but potentially serious complication associated with bone-modifying agents.
Both studies suggested every-3-months dosing of zoledronic acid could be effective. However, Dr. Roodman noted that both studies had limitations that need to be considered, including small numbers of myeloma patients, limited duration of therapy studied, and a high dropout rate in the case of one study. Due to those limitations, “it’s very difficult to draw conclusions about this today,” Dr. Roodman said.
Dr. Roodman reported that he had a consulting or advisory role with Amgen.
EXPERT ANALYSIS FROM ASCO 2018