Andreas Engert, MD
The European Commission (EC) has approved nivolumab (Opdivo) for the treatment of patients with relapsed/refractory classical Hodgkin lymphoma (cHL) after autologous stem cell transplant (ASCT) and treatment with brentuximab vedotin (Adcetris), according to Bristol-Myers Squibb (BMS), the manufacturer of the PD-1 inhibitor.
The approval was based on an objective response rate (ORR) of 66% (95% CI, 56-76; n = 63) in a combined analysis of 95 patients with relapsed or refractory cHL who received nivolumab either in the phase II CheckMate-205 trial or the phase I CheckMate-039 trial. The complete response rate was 6% (n = 6) and the partial response rate was 60% (n = 57). The 12-months progression-free survival rate was 57%.
The EC’s approval decision followed a positive recommendation from the Committee for Medicinal Products for Human Use. Nivolumab is now approved for use in relapsed or refractory cHL in the 28 countries of the European Union (EU), making it the first anti¬–PD-1 agent approved in the EU for a hematologic malignancy.
“As a practicing hematologist, I have experienced the challenge of managing classical Hodgkin lymphoma and the need among previously treated patients,” Andreas Engert, MD, lead investigator and professor of Internal Medicine, Hematology and Oncology, University Hospital of Cologne, Cologne, Germany, said in a statement.
“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,” added Engert.
The CheckMate-205 and -039 trials were both open-label, multicenter, multicohort studies. CheckMate-205 included exclusively cHL patients and Checkmate-039 was a dose escalation study that included a cohort of patients with cHL. The cHL populations in both studies had relapsed or progressed after failure of autologous HSCT and posttransplantation brentuximab vedotin.
The median time to response in the integrated population from the 2 trials was 2 months (range, 0.7-11.1) and the median duration of response was 13.1 months (range, 0+ to 23.1+). Twenty-three percent of patients had stable disease.
The safety analysis included 263 patients, comprising 240 patients from CheckMate-205 and 23 patients from CheckMate-039. The most frequently reported adverse events (AEs) included fatigue (32%), upper respiratory tract infection (28%), pyrexia (24%), diarrhea (23%), and cough (22%).
Serious AEs occurred in 21% of patients, with those occurring in ≥1% of patients including infusion-related reaction, pneumonia, pleural effusion, pyrexia, rash, and pneumonitis. AEs led to discontinuation for 4.2% of these patients and 23% had a dose delay due to an AE. Six of 40 patients died of complications of allogeneic HSCT after nivolumab.
“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,” Emmanuel Blin, senior vice president and chief strategy officer, Bristol-Myers Squibb, said in a statement.