FDA Approves Nivolumab for Hodgkin Lymphoma

Anas Younes, MD

The FDA granted nivolumab (Opdivo) accelerated approval for the treatment of patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and posttransplantation brentuximab vedotin (Adcetris).

The approval was based on an objective response rate (ORR) of 65% (95% CI, 55-75; n = 62) 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. Nivolumab is now the first PD-1 inhibitor approved for a hematologic malignancy.

“This approval is remarkable for many reasons. It is the second drug in history to be approved for patients with relapsed Hodgkin lymphoma. In addition, within this indication, nivolumab produced the highest response rate compared to any other cancer. More importantly, it seems that nivolumab can be combined with brentuximab vedotin at full doses of each agent, creating an excitement about the potential for changing the future therapy of Hodgkin lymphoma,” Anas Younes, MD, chief of the Lymphoma Service at Memorial Sloan Kettering Cancer Center, said in an interview with OncLive.

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 full results from CheckMate-205 will be presented in June at the 2016 ASCO Annual Meeting, according to Bristol-Myers Squibb (BMS), the manufacturer of nivolumab.

Patients were enrolled in the 2 CheckMate trials regardless of PD-L1 status. The median age for the 95-patient efficacy analysis was 37 years (range, 18-72) and most patients were male (64%) and white (87%). All patients had an ECOG performance status ≤2.

Nivolumab was administered at 3 mg/kg IV over 60 minutes every 2 weeks until disease progression or unacceptable toxicity. The median number of prior systemic regimens received was 5 (range, 3-15). The median duration of therapy was 8.3 months (range, 1.9-24), and patients received a median of 17 doses (range, 3-48).

The ORR of 65% was composed of a 7% (95% CI, 3-15; n = 7) complete remission rate and a 58% partial remission rate (95% CI, 47-68; n = 55). The median duration of response was 8.7 months and the median time to response was 2.1 months (range, 0.7-5.7 months).

The safety analysis included 263 patients, comprising 240 patients from CheckMate-205 and 23 patients from CheckMate-039. The median patient age in the safety population was 34 years (range, 18-72), 98% had received autologous HSCT (0 allogeneic HSCT), and 74% had prior brentuximab vedotin. Patients had received a median of 4 (range, 1-15) prior systemic regimens. The median number of nivolumab doses in this population was 10 (range, 1-48) and the median duration of therapy was 4.8 months (range, 0.3-24).

Adverse events (AEs) led to discontinuation for 4.2% of these patients and 23% had a dose delay due to an AE. The most frequently reported AEs (≥20% of patients) 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. There were 10 patient deaths due to causes other than disease progression, including 6 from complications of allogeneic HSCT.

The FDA reported that a new “Warning and Precaution” was issued for complications of allogeneic HSCT following nivolumab therapy. The warning recommends that healthcare professionals should closely monitor patients for signs of transplant-related complications, such as hyperacute GVHD, severe acute GVHD, steroid-requiring febrile syndrome, hepatic veno-occlusive disease, and other immune-mediated adverse reactions. The FDA has also required that BMS conduct further research to evaluate the safety of allogeneic HSCT following administration of nivolumab.

The supplemental biologics license application for nivolumab in cHL was submitted by BMS under a 2014 breakthrough therapy designation the PD-1 inhibitor received for the treatment of patients with Hodgkin lymphoma following autologous stem cell transplant and brentuximab vedotin. The accelerated approval of nivolumab in cHL is contingent on the confirmatory outcomes of a phase III trial.

“Today’s approval of Opdivo delivers a transformational and exciting new option for these patients and the hematologists who treat them. By expanding this immuno-oncology therapy into a hematologic malignancy, we continue to deliver upon our unwavering commitment to provide treatments that work directly with the body’s immune system for patients who are in need of new options,” Chris Boerner, head of US Commercial at BMS, said in a statement.