Nivolumab Results in High Rate of Response in Refractory Classical Hodgkin's Lymphoma

·         in this single-arm, phase II study, the authors evaluated the efficacy and safety of nivolumab monotherapy in 80 adults with recurrent classical Hodgkin's lymphoma following failure of autologous stem-cell transplantation and brentuximab vedotin. After a median of 8.9 months of follow-up, 66.3% of patients achieved an IRRC-assessed objective response. Common adverse effects included fatigue (25%), reaction to the infusion (20%), and rash (16%). The most common grade ≥3 adverse events were neutropenia (5%) and increased lipase concentrations (5%). There were 3 deaths during the study period but none was thought to be related to therapy.

           Treatment with nivolumab results in a response in the majority of patients with refractory                  Hodgkin's lymphoma, and the safety profile is acceptable. Nivolumab may represent a                   novel treatment option for this population.

Hodgkin’s lymphoma is highly curable with chemotherapy with or without radiation therapy. High-dose chemotherapy with stem cell support is standard treatment for fit patients relapsing or refractory following front-line chemotherapy and cures approximately 50% of those patients. Brentuximab vedotin, an antibody–drug conjugate, is associated with a response rate that is approximately twice as high as that with any single conventional chemotherapy agent in relapsed and refractory patients following autologous stem cell transplantation. However, it is also a form of chemotherapy. There remains a small number of patients with Hodgkin’s lymphoma, perhaps 10%, who are truly chemotherapy-resistant. That is why it is exciting that at last a treatment that is not chemotherapy is effective for these patients. Nivolumab and pembrolizumab, antibodies that target lymphocyte PD-1 and result in release of checkpoint inhibition of anti-tumor T cells, resulted in high response rates in small expansion cohorts in phase I trials of these agents in relapsed and refractory patients following autologous stem cell transplantation.1,2 Younes et al report on the results of a larger phase II trial of nivolumab in 80 Hodgkin’s patients with relapsed or refractory disease after autologous stem cell transplant and brentuximab vedotin.3 This trial confirms the high response rate (66% with 9% CR) and resulted in accelerated FDA approval of nivolumab for this patient population. Preliminary results from a phase II trial of pembrolizumab are similar.4 Immune therapy provides a new approach, different from chemotherapy, which has the potential to improve the outcome for these resistant Hodgkin’s lymphoma patients.