Journal Article

Nivolumab in patients with relapsed or refractory peripheral T-cell lymphoma: modest activity and cases of hyperprogression

Feldman, Andrew L, Atherton, Pamela J, Ansell, Stephen M, Bennani, N Nora, Kim, Hyo Jin, Thanarajasingam, Gita, Micallef, Ivana N, Nowakowski, Grzegorz S, Pederson, Levi D, Witzig, Thomas

2022

Overview

Peripheral T-cell lymphomas (PTCL), a heterogeneous group of mature aggressive non-Hodgkin’s lymphomas, carry a worse prognosis for most subtypes when compared with their B-cell counterparts. Despite recent approval of newer therapies, the outlook for patients with relapsed/refractory (RR) PTCL remains poor and new treatment strategies are clearly needed. Targeting the profoundly immunosuppressive tumor microenvironment in PTCL is one such approach. To determine whether immune checkpoint blockade targeting program death receptor 1 would be effective in PTCL, we conducted an investigator-initiated phase 2 prospective study of single-agent nivolumab for RR PTCL. We report here results of the pre-specified interim analysis.MethodsThe primary objective was to assess the overall response rate (ORR). Secondary objectives were to assess safety and tolerability of nivolumab in PTCL and to assess progression-free survival (PFS), duration of response (DOR) and overall survival (OS). Hyperprogressive disease (HPD) was defined as time-to-treatment failure of less than or equal to one month from initiation of therapy.ResultsTwelve patients who received at least one cycle of nivolumab were included in this interim analysis. Half (6/12) of the patients had angioimmunoblastic T-cell lymphoma (AITL), 3/12 had PTCL, not otherwise specified. Most (11/12) were advanced stage, had extranodal disease (97.1%) and had received a prior autologous stem cell transplant (50%). The ORR was 33% (95% CI: 12.3 to 63.7%) with two complete response and two partial response. The median PFS was however short at 2.7 months (95% CI: 1.5 to NE); and the median OS was 6.7 months (95% CI: 3.4 to NE). The median DOR was also short at 3.6 months (95% CI: 1.9 to NE). HPD occurred in four patients, three of whom had AITL. Observed grade 3 and higher adverse events (AEs) were non-hematologic in 5/12 (42%), while hematologic AEs were seen in 3/12 (25%).ConclusionsNivolumab had modest clinical activity in R/R PTCL. Due to a high number of hyperprogression and short DOR, a decision was made to halt the study. These findings likely reflect the distinct biology of PTCL and should be considered when designing future studies using checkpoint inhibitors in these diseases.Trial registration numberNCT03075553.

• Publisher: BMJ Publishing Group Ltd,BMJ Publishing Group LTD,BMJ Publishing Group
• Subject: Blood cancer / Cancer / Cell death / Clinical Trials, Phase II as Topic / Clinical/Translational Cancer Immunotherapy / Disease Progression / Gene expression / Hematologic Neoplasms / Humans / Immunotherapy / Kinases / Ligands / Lymphocytes / Lymphoma / Lymphoma, T-Cell, Peripheral - drug therapy / Lymphoma, T-Cell, Peripheral - pathology / Medical imaging / Medical prognosis / Monoclonal antibodies / Neoplasm Recurrence, Local - drug therapy / Nivolumab - pharmacology / Nivolumab - therapeutic use / Oncology / Patients / Prognosis / Programmed Cell Death 1 Receptor / Prospective Studies / Response rates / Software / Stem cell transplantation / Targeted cancer therapy / Tumor Microenvironment