FDA Grants Accelerated Approval to Nivolumab for Hodgkin Lymphoma

May 18, 2016

The FDA has granted an accelerated approval to nivolumab for patients with classical Hodgkin lymphoma following relapse or progression after autologous hematopoietic stem cell transplantation and post-transplantation brentuximab vedotin.

Anas Younes, MD

The FDA has granted an accelerated approval to nivolumab (Opdivo) for patients with classical Hodgkin lymphoma (cHL) following relapse or progression after autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation brentuximab vedotin (Adcetris).

The decision, which makes nivolumab the first FDA-approved PD-1 inhibitor for a hematologic malignancy, was based on data from 95 patients in two single-arm studies. Data from the trials were submitted through a breakthrough therapy designation that had been received in 2014. In combined data from the 2 studies, the objective response rate (ORR) with nivolumab was 65% for patients with relapsed or refractory cHL.

“It is important to have new treatment options for patients with difficult-to-treat diseases who have exhausted the current available options. Because of the unique pathology and biology of classical Hodgkin lymphoma, it makes sense from a scientific standpoint to investigate a PD-1 inhibitor,” Anas Younes, MD, medical oncologist and chief of Lymphoma Service, Memorial Sloan Kettering Cancer Center, said in a statement. “The recent clinical data with Opdivo in patients with classical Hodgkin lymphoma who have relapsed or progressed after auto-HSCT and post-transplantation brentuximab vedotin is encouraging and has the potential to impact our approach to treating these individuals in the future.”

The trials that were instrumental in the approval of nivolumab (CheckMate-205 and CheckMate-039) were both open-label, multicenter, multicohort studies. Data from CheckMate-205, which included exclusively patients with cHL, has not yet been presented. Data from this study were released in the label for the PD-1 inhibitor. CA209-039 was a dose escalation study that included a group of patients with cHL. Data from this study were initially presented at the 2014 ASH Annual Meeting, and were subsequently updated as data matured.

Patients with cHL in both studies had relapsed or progressed after failure of autologous HSCT and post-transplantation brentuximab vedotin, and were enrolled regardless of PD-L1 status. The median patient age was 37 years (range, 18-72) and most patients were male (64%) and white (87%).

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 months), and patients received a median of 17 doses.

The ORR of 65% was composed of a 7% (n = 7) complete remission rate and a 58% partial remission rate (n = 55). 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 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 months).

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 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.

“Today’s approval of Opdivo delivers a transformational and exciting new option for these patients and the hematologists who treat them," Chris Boerner, Head of US Commercial, Bristol-Myers Squibb, said in a statement. "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.”