PD-1 blockade with nivolumab was safe and achieved objective responses in patients with lymphoma.

  • Major finding: PD-1 blockade with nivolumab was safe and achieved objective responses in patients with lymphoma.

  • Approach: A phase I, open-label, cohort-expansion study evaluated nivolumab in multiple lymphoma subtypes.

  • Impact: PD-1 blockade may have antitumor activity in a variety of B- and T-cell lymphomas.

Immune checkpoint blockade with anti–PD-1 antibodies including nivolumab and pembrolizumab has achieved durable response in patients with solid tumors and Hodgkin lymphoma. However, nivolumab has not yet been tested across hematologic malignancies that express PD-1/PD-L1. Lesokhin and colleagues performed a phase I, open-label, dose-escalation, cohort-expansion study to determine the safety and efficacy of nivolumab in B-cell lymphoma, T-cell lymphoma, and multiple myeloma. A total of 81 patients with refractory or relapsed lymphoma were enrolled: 10 with follicular lymphoma, 11 with diffuse large B-cell lymphoma, 10 with other B-cell lymphomas, 13 with mycosis fungoides, 5 with peripheral T-cell lymphoma, 5 with other T-cell lymphomas, and 27 with multiple myeloma. The primary objective was to evaluate safety, and secondary objectives included evaluation of antitumor activity. Objective responses were achieved in 40% of patients with follicular lymphoma, 36% of patients with diffuse large B-cell lymphoma, 15% of patients with mycosis fungoides, and 40% of patients with peripheral T-cell lymphoma. Response durations ranged from 6 weeks to more than 81 weeks. A total of 4 complete responses were observed, 2 in patients with diffuse large B-cell lymphoma, 1 in a patient with follicular lymphoma, and 1 in a patient with multiple myeloma after radiotherapy. However, responses were not observed in other patients with multiple myeloma. Nivolumab was well tolerated; 65% of patients experienced drug-related adverse events, which were largely grade 1 or 2, although 15% of patients discontinued treatment due to drug-related adverse events. One patient with small lymphocytic B-cell lymphoma died of pneumonitis. Taken together, the results of this study indicate that nivolumab has a favorable safety profile and antitumor activity in non-Hodgkin lymphoma, and prompted continued evaluation of nivolumab in relapsed or refractory follicular lymphoma and diffuse large B-cell lymphoma in ongoing phase II trials.

Lesokhin AM, Ansell SM, Armand P, Scott EC, Halwani A, Gutierrez M, et al. Nivolumab in patients with relapsed or refractory hematologic malignancy: preliminary results of a phase Ib study. J Clin Oncol 2016 Jun 6 [Epub ahead of print].

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