FDA Approves Opdivo for Classical Hodgkin Lymphoma

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

The approval was based on an objective response rate (ORR) of 65 percent (62 patients) in 95 patients enrolled in two single-arm trials (Trial 8 and Trial 9) of Opdivo in patients with relapsed or refractory cHL. Opdivo 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 Opdivo can be combined with Adcetris at full doses of each agent, creating an excitement about the potential for changing the future therapy of Hodgkin lymphoma,” Anas Younes, chief of the Lymphoma Service at Memorial Sloan Kettering Cancer Center, said.

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 Adcetris. 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 Opdivo.

Patients were enrolled in each study regardless of PD-L1 status. The median patient age was 37 years (range, 18-72) and most patients were male (64 percent) and white (87 percent). Opdivo was administered at three mg/kg IV over 60 minutes every two 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 months), and patients received a median of 17 doses.

The ORR of 65 percent was composed of a 7 percent (7 patients) complete remission rate and a 58 percent partial remission rate (55 patients). The median duration of response was 8.7 months and the median time to response was 2.1 months.

The safety analysis included 263 patients, comprising 240 patients from Trial 8 and 23 patients from Trial 9. The median patient age in the safety population was 34 years (ranging from 18 to 72), 98 percent had received autologous HSCT (0 allogeneic HSCT), and 74 percent had prior Adcetris. Patients had received a median of four (range, 1-15) prior systemic regimens. The median number of Opdivo doses in this population was 10 (ranging from 1 to 48) and the median duration of therapy was 4.8 months (ranging from 0.3 to 24 months).

Adverse events (AEs) led to discontinuation for 4.2 percent of these patients and 23 percent had a dose delay due to an AE. The most frequently reported AEs (at least 20 percent of patients) included fatigue (32 percent), upper respiratory tract infection (28 percent), pyrexia (24 percent), diarrhea (23 percent) and cough (22 percent). Serious AEs occurred in 21 percent of patients, with those occurring in at least 1 percent 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 six from complications of allogeneic HSCT.

The FDA reported that a new “Warning and Precaution” was issued for complications of allogeneic HSCT following Opdivo therapy. The FDA recommended 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 Bristol-Myers Squibb, the manufacturer of Opdivo, conduct further research to evaluate the safety of allogeneic HSCT following administration of Opdivo.

The supplemental biologics license application for Opdivo 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 Adcetris. The accelerated approval of Opdivo in cHL is contingent on the confirmatory outcomes of a phase 3 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.