European Commission has approved Bristol-Myers Squibb’s Opdivo (nivolumab) for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL) after autologous stem cell transplant (ASCT) and treatment with brentuximab vedotin.
Bristol-Myers noted that Opdivo is now the first and only PD-1 inhibitor approved for a hematologic malignancy in the European Union (EU). This approval allows for the expanded marketing of Opdivo in relapsed or refractory cHL in all 28 Member States of the EU.
The company explained it its press release issued on Tuesday that the approval is based on an integrated analysis of data from the Phase 2 CheckMate -205 and the Phase 1 CheckMate -039 trials, evaluating patients with relapsed or refractory cHL after ASCT and treatment with brentuximab vedotin. In the subset of patients in the efficacy population (n=95), the primary endpoint of objective response rate (ORR) as assessed by an independent radiologic review committee was 66% (95% CI: 56-76; 63/95 patients). The percentage of patients with a complete response was 6% (95% CI: 2-13; 6/95 patients), and the percentage of patients with a partial response was 60% (95% CI: 49-70; 57/95 patients). At 12 months, the progression-free survival rate was 57% (95% CI: 45-68). Opdivo is associated with warnings and precautions including immune-related: pneumonitis, colitis, hepatitis, nephritis and renal dysfunction, endocrinopathies, rash, and other adverse reactions; infusion reactions, and complications of allogeneic hematopoietic stem cell transplantation (HSCT) in cHL after Opdivo.
Emmanuel Blin, senior vice president and chief strategy officer, Bristol-Myers Squibb, commented, “We’re incredibly proud of this approval for Opdivo and what it means for adult patients with relapsed or refractory classical Hodgkin lymphoma after autologous stem cell transplant and treatment with brentuximab vedotin, as it marks the first and only PD-1 inhibitor approved for a hematologic malignancy in the EU. This also is Bristol-Myers Squibb’s second Immuno-Oncology agent approved for a blood cancer in the EU within just six months.”
“As a practicing hematologist, I have experienced the challenge of managing classical Hodgkin lymphoma and the need among previously treated patients,” said Andreas Engert, M.D., lead investigator and professor of Internal Medicine, Hematology and Oncology, University Hospital of Cologne, Cologne, Germany. “It is incredibly exciting that with today’s approval of Opdivo for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma after autologous stem cell transplant and treatment with brentuximab vedotin in the EU, we now have an entirely new treatment approach that has shown impressive response rates and durability of response in this difficult-to-treat population.”
In the integrated analysis of data from CheckMate -205 and CheckMate -039, the median time to response was 2.0 months (range 0.7-11.1), and among responders, the duration of response was maintained over time for a median of 13.1 months (95% CI: 9.5-NE; range 0.0+, 23.1+). Stable disease was observed in 23% of patients. In a post-hoc analysis of the 80 patients in CheckMate -205 cohort B, it was found 37 patients had no response to prior brentuximab vedotin treatment. Among these 37 patients, treatment with Opdivo resulted in an ORR of 59.5% (22/37), and the median duration of response was 13.14 months Bristol-Myers explained.
The company further explained that the safety of Opdivo in cHL was evaluated in 263 adult patients from CheckMate -205 (n=240) and CheckMate -039 (n=23). Among these patients (total safety population: n=263), serious adverse events (AEs) occurred in 21% of patients. The most common serious AEs (reported in at least 1% of patients) were infusion-related reaction, pneumonia, pleural effusion, pyrexia, rash and pneumonitis. The most common AEs (reported in at least 20% of patients) were fatigue (32%), upper respiratory tract infection (28%), pyrexia (24%), diarrhea (23%), and cough (22%). Twenty-three percent of patients had a dose delay for an AE, and 4.2% of patients discontinued treatment due to AEs. Six out of 40 patients died from complications of allogeneic HSCT after Opdivo, and these 40 patients had a median follow-up from subsequent allogeneic HSCT of 2.9 months (range: 0-22).