On May 17, 2016, the U.S. Food and Drug Administration (FDA) granted accelerated approval to the programmed cell death protein 1 (PD‑1) inhibitor, nivolumab (Opdivo), for the treatment of patients with classical Hodgkin lymphoma that has relapsed or progressed after autologous hematopoietic stem cell transplantation and post-transplantation brentuximab vedotin (Adcetris).
The approval was based on combined analysis of two single-arm, multicenter trials of nivolumab in adults with relapsed or refractory classical Hodgkin lymphoma.1,2 Efficacy was evaluated in 95 patients previously treated with autologous hematopoietic stem cell transplantation and post-transplantation brentuximab vedotin. Patients had a median of five prior systemic regimens and received a median of 17 doses of nivolumab. Single-agent nivolumab produced a 65% overall response rate, with 58% partial remission and 7% complete remission. The median time-to-response was 2.1 months. The estimated median duration of response was 8.7 months.
Safety was evaluated in 263 patients with relapsed or refractory classical Hodgkin lymphoma. Overall, 98% of patients had received autologous hematopoietic stem cell transplantation. Patients received a median of 10 doses of nivolumab at the approved dose schedule.
The most common adverse reactions of any grade were fatigue, upper respiratory tract infection, cough, pyrexia, and diarrhea. The most common serious adverse events (1%–3% of patients), were pneumonia, pleural effusion, pneumonitis, pyrexia, infusion-related reaction, and rash.
A new “Warning and Precaution” was issued for complications of allogeneic hematopoietic stem cell transplantation after nivolumab. Transplant-related deaths have occurred, and health-care professionals should follow patients closely for early evidence of transplant-related complications, such as hyperacute graft-vs-host disease, severe acute graft-vs-host disease, steroid-requiring febrile syndrome, hepatic veno-occlusive disease, and other immune-mediated adverse reactions. The FDA has required the manufacturer to further study the safety of allogeneic hematopoietic stem cell transplant after nivolumab.
Continued approval for the classical Hodgkin lymphoma indication may be contingent upon verification of clinical benefit through a randomized phase III trial. Nivolumab also has Orphan Drug status for the treatment of Hodgkin lymphoma. This application was granted Priority Review and was approved under the FDA’s Accelerated Approval Program.
The recommended dose-schedule of nivolumab is 3 mg/kg intravenously every 2 weeks until disease progression or unacceptable toxicity. Full prescribing information is available at FDA.gov. ■
2. Ansell S, et al: Nivolumab in patients with relapsed or refractory classical Hodgkin lymphoma: Clinical outcomes from extended follow-up of a phase 1 study (CA209-039). 2015 ASH Annual Meeting. Abstract 583.