Nivolumab for Relapsed/Refractory Diffuse Large B-Cell Lymphoma in Patients Ineligible for or Having Failed Autologous Transplantation: A Single-Arm, Phase II Study
Ansell, Stephen M; Minnema, Monique C; Johnson, Peter; Timmerman, John M; Armand, Philippe; Shipp, Margaret A; Rodig, Scott J; Ligon, Azra H; Roemer, Margaretha G M; Reddy, Nishitha; Cohen, Jonathon B; Assouline, Sarit; Poon, Michelle; Sharma, Manish; Kato, Kazunobu; Samakoglu, Selda; Sumbul, Anne; Grigg, Andrew
(2019) Journal of clinical oncology : official journal of the American Society of Clinical Oncology, volume 37, issue 6, pp. 481 - 489
(Article)
Abstract
PURPOSE: Treatment options are limited for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Tumor cells can exploit the programmed death-1 checkpoint pathway to evade immune surveillance. In the current study, we evaluated the efficacy and safety of programmed death-1 blockade by nivolumab in patients with relapsed/refractory DLBCL. METHODS: In
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this phase II, open-label study, patients with relapsed/refractory DLBCL who were ineligible for autologous hematopoietic cell transplantation (auto-HCT) or who had experienced failure with auto-HCT received nivolumab 3 mg/kg every 2 weeks. We assessed the efficacy and safety of nivolumab as well as genetic alterations of 9p24.1. RESULTS: Among 121 treated patients, patients in the auto-HCT-failed cohort (n = 87) received a median of four nivolumab doses and a median of three doses were administered to those in the auto-HCT-ineligible cohort (n = 34). At a median follow-up of 9 months in the auto-HCT-failed cohort and 6 months in the auto-HCT-ineligible cohort, independently assessed objective response rates were 10% and 3%, and median durations of response were 11 and 8 months, respectively. Median progression-free survival and overall survival were 1.9 and 12.2 months in the auto-HCT-failed cohort and 1.4 and 5.8 months in the auto-HCT-ineligible cohort respectively. All three patients with complete remission-3% of the auto-HCT-failed cohort-had durable response (11 or more, 14 or more, and 17 months). Treatment-related grade 3 and 4 adverse events were reported in 24% of patients. The most common were neutropenia (4%), thrombocytopenia (3%), and increased lipase (3%). Of all evaluable samples for 9p24.1 analysis, 16% exhibited low-level copy gain and 3% had amplification. CONCLUSION: Nivolumab monotherapy is associated with a favorable safety profile but a low overall response rate among patients with DLBCL who are ineligible for auto-HCT or who experienced failure with auto-HCT. Genetic alterations of 9p24.1 are infrequent in DLBCL.
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Keywords: Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Immunological/adverse effects, Chromosomes, Human, Pair 9, Disease Progression, Female, Hematopoietic Stem Cell Transplantation/adverse effects, Humans, Lymphoma, Large B-Cell, Diffuse/drug therapy, Male, Middle Aged, Nivolumab/adverse effects, Programmed Cell Death 1 Receptor/antagonists & inhibitors, Progression-Free Survival, Remission Induction, Time Factors, Transplantation, Autologous/adverse effects, Treatment Failure, Young Adult, Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology
Note: Funding Information: Supported by Bristol-Myers Squibb, which also funded medical writing support. Also supported by the Harold and Virginia Lash Foundation (P.A.); US National Institutes of Health Grant No. R01CA161026 and the Miller Fund (M.A.S.); the Center for Immuno-Oncology of the Dana-Farber Cancer Institute (S.J.R.); and the American Society of Hematology and Lymphoma Research Foundation (388017; J.B.C.). Publisher Copyright: © 2019 by American Society of Clinical Oncology.
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