Nivolumab Safe, Effective in Relapsed/Refractory Lymphoma

June 18, 2015

Treatment with the PD-1 inhibitor nivolumab demonstrated durable objective response rates in patients with classical Hodgkin lymphoma, diffuse large B-cell lymphoma, and follicular lymphoma.

Philippe Armand, MD

Treatment with the PD-1 inhibitor nivolumab (Opdivo) demonstrated durable objective response rates (ORR) in patients with classical Hodgkin lymphoma, diffuse large B-cell lymphoma (DLBCL), and follicular lymphoma (FL), according to findings from the CheckMate-039 study. Findings from the phase I study were presented by Philippe Armand, MD, from the Dana-Farber Cancer Center, at the 20th Congress of the European Hematology Association (EHA).

"Encouraging, durable objective responses were observed in classical Hodgkin lymphoma, DLBCL and FL, including complete response and partial response," the authors of the study wrote. "Nivolumab treatment remains safe and tolerable with a safety profile similar to that in solid tumors, and further analysis is warranted in classical Hodgkin lymphoma and selected B-NHLs and T-NHLs."

In the study, 105 patients were treated with nivolumab at 1 mg/kg and 3 mg/kg, in a dose escalation design. Treatment was administered every 2 weeks for 2 years. Overall, there were 23 patients with classical Hodgkin lymphoma, 31 with B-cell non-Hodgkin lymphoma (B-NHL), 23 with T-cell NHL, 27 with multiple myeloma, and 1 with chronic myeloid leukemia (CML).

All patients in the study were heavily pretreated, having received ≥3 prior regimens. Seventy-five percent of patients had received prior autologous stem cell transplant (ASCT) in the classical Hodgkin lymphoma arm. In the remaining arms, 56%, 13%, and 9% had received ASCT for multiple myeloma, B-NHL, and T-NHL, respectively. The primary endpoint of the study was safety, with a secondary outcome measure focused on efficacy.

In patients with classical Hodgkin lymphoma, the ORR was 87%, with a complete response (CR) rate of 17%. The median response duration was not yet reached, with responses ongoing in 50% of patients. For those with multiple myeloma, the stable disease rate was 63%.

For those with B-NHL, the ORR was 26%, with a 10% CR rate. The ORR was highest in patients with B-cell FL (n = 10) at 40%. In those with DLBCL (n = 11), the ORR was 36%, with a median duration of response of 22.1 weeks. Patients with other types of B-cell lymphoma enrolled in the study (n = 10) did not experience a response with nivolumab.

In the T-NHL arm, the ORR was 17%, which was comprised entirely of partial responses (PR). In patients with cutaneous T-cell lymphoma mycosis fungoides (n = 13) the ORR was 15%, with all responses ongoing. In the peripheral T-cell lymphoma (n = 5), the ORR was 40%. Patient with other types of T-NHL did not experience responses with nivolumab.

The median duration of response across all arms was 62 weeks. Drug-related adverse events occurred in the majority of patients treated with nivolumab (67%). The most common adverse events were fatigue (15%), rash (11%), diarrhea (9%), pneumonitis (9%), pruritus (9%), pyrexia (8%), thrombocytopenia (7%), and decreased appetite (7%). The most common serious adverse event was pneumonitis (5%).

Ten patients in the classical Hodgkin lymphoma arm who responded to treatment discontinued nivolumab over the course of the study: 6 to undergo transplant, 3 as a result of progressive disease, and 1 for toxicity.

In May 2014, nivolumab received a breakthrough therapy designation from the FDA for the treatment of patients with Hodgkin lymphoma following autologous stem cell transplant (ASCT) and brentuximab vedotin (Adcetris). Additionally, the PD-1 inhibitor nivolumab has been investigated heavily for its potential to elicit an antitumor immune response across a variety of tumors. The drug is approved as a treatment for patients with non—small cell lung cancer and for those with metastatic melanoma.

Armand P, Timmerman J, Lesokhin A, et al. Nivolumab in patients with relapsed or refractory lymphoid malignancies and classical Hodgkin lymphoma: updated safety and efficacy results of a phase 1 study (CA209-039). Presented at: 20th Congress of the European Hematology Association (EHA); Sunday, June 14, 2015; Vienna, Austria. Abstract #S808.