TY - JOUR
T1 - Efficacy and safety results from CheckMate 140, a phase 2 study of nivolumab for relapsed/refractory follicular lymphoma
AU - Armand, Philippe
AU - Janssens, Ann
AU - Gritti, Giuseppe
AU - Radford, John
AU - Timmerman, John
AU - Pinto, Antonio
AU - Mercadal Vilchez, Santiago
AU - Johnson, Peter
AU - Cunningham, David
AU - Leonard, John P.
AU - Rodig, Scott J.
AU - Martín-Regueira, Patricia
AU - Sumbul, Anne
AU - Samakoglu, Selda
AU - Tang, Hao
AU - Ansell, Stephen M.
N1 - Funding Information:
The biomarker studies involving sIL-2Rα were supported in part by funding from the Leukemia and Lymphoma Society. Editorial assistance was funded by Bristol Myers Squibb. P.A. gratefully acknowledges the support of the Harold and Virginia Lash Foundation and the Leukemia and Lymphoma Society. D.C. is funded by the National Institute for Health Research Biomedical Research Centre at the Royal Marsden and Institute of Cancer Research. S.M.A. acknowledges support from the Jaime Erin Follicular Research Consortium and the Leukemia and Lymphoma Society.
Funding Information:
Conflict-of-interest disclosure: P.A. has consulted for Merck, Bristol Myers Squibb, Pfizer, Affimed, Adaptive, Infinity, ADC Therapeutics, and Celgene; received institutional research funding from Merck, Bristol Myers Squibb, Affimed, Adaptive, Roche, Tensha, Otsuka, Sigma Tau, Genentech, and IGM; and received honoraria from Merck and Bristol Myers Squibb. A.J. received an educational grant from Janssen; travel grants from Janssen, Celgene, AbbVie, and Roche; speaker fees from Janssen, Roche, AbbVie, Novartis, Amgen, Sanofi-Genzyme, and Celgene; and has consulted for Janssen, Roche, Gilead, AbbVie, Novartis, Amgen, and Sanofi-Genzyme. G.G. has consulted or advised for Autolus and Bioveloc ITA; served on a speakers' bureau for Amgen; received research funding from Gilead; and received travel and accommodation from Roche, AbbVie, and Becton Dickinson. J.R. has received honoraria or advised for Takeda, Seattle Genetics, ADC Therapeutics, and Bristol Myers Squibb; received research funding from Takeda and ADC Therapeutics; and has stock ownership (spouse) in AstraZeneca and GlaxoSmithKline. J.T. holds stock or other ownership in Genmab, Corvus, Marker Therapeutics, and Bluebird Bio; has served in a consulting or advisory role with Kite, a Gilead Company, Celgene, Immune Design, and Celldex Therapeutics; has received research funding from Bristol Myers Squibb, Kite, a Gilead Company, Spectrum Pharmaceuticals, and Merck; and has received travel, accommodations, or expenses from Bristol Myers Squibb and Kite, a Gilead Company. A.P. has served on speakers' bureaus for Roche, Celgene, Bristol Myers Squibb, Merck Sharp & Dohme, Servier, and Novartis. P.J. has received honoraria from Takeda, Bristol Myers Squibb, Novartis, Celgene, Kite Pharma, Genmab, and Incyte; has had a consulting or advisory role with Janssen Pharmaceuticals, Epizyme, and Boehringer Ingelheim; has received institutional research funding from Epizyme and Janssen Pharmaceuticals; has patents, royalties, or other intellectual property (combined use of Fc γ RIIb (CD32b) and CD20, specific antibodies, WO Patent, PCT/GB2011/051572; EU11760819.0); and has received travel, accommodation, and expenses from Zenyaku Kogyo. D.C. has received research funding from Amgen, Sanofi, Merrimack, AstraZeneca, Celgene, MedImmune, Bayer, 4SC, Clovis, Eli Lilly, Janssen, and Merck. J.P.L. has had a consulting or advisory role with Sutro, Gilead, Kite, AstraZeneca, Celgene, Roche/Genentech, ADC Therapeutics, Sandoz, Karyopharm, Miltenyi, Regeneron, and MEI Pharma. S.J.R. has received research funding from Bristol Myers Squibb, Affimed, KITE/Gilead, and Merck. P.M.-R. is an employee of and has equity ownership in Bristol Myers Squibb. A.S. is an employee of Bristol Myers Squibb. S.M.A. has received research funding from Bristol Myers Squibb, Merck, Seattle Genetics, Takeda, AI Therapeutics, Regeneron, Affimed, Trillium, and Pfizer. The remaining authors declare no competing financial interests.
Publisher Copyright:
© 2021 American Society of Hematology
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/2/4
Y1 - 2021/2/4
N2 - Nivolumab, an anti-programmed death-1 (PD-1) monoclonal antibody, showed promising activity in relapsed or refractory (R/R) follicular lymphoma (FL) in a phase 1 study. We conducted a phase 2 trial to further evaluate its efficacy and safety in patients with R/R FL and to explore biomarkers of response. Patients with R/R FL and at least 2 prior lines of therapy, each containing a CD20 antibody or an alkylating agent, were treated with nivolumab 3 mg/kg every 2 weeks. The primary end point was objective response rate (ORR) assessed by an independent radiologic review committee. Biomarker analyses included gene expression profiling and multiplex immunofluorescence studies of pretreatment tumor samples. A total of 92 patients were treated. After a minimum follow-up of 12 months, ORR was 4% (4 of 92 patients). Median progression-free survival (PFS) was 2.2 months (95% confidence interval [CI], 1.9-3.6 months). Median duration of response was 11 months (95% CI, 8-14 months). Exploratory analyses suggested that responders had significantly higher proportion of CD3+ T cells in the tumor microenvironment than nonresponders, but no significant differences in PD-1 or programmed death-ligand 1 expression were observed. High expression of a set of tumor-associated macrophage genes was associated with reduced PFS (hazard ratio, 3.28; 95% CI, 1.76-6.11; P = .001). The safety profile was consistent with previous reports of nivolumab. In conclusion, nivolumab monotherapy was associated with very limited activity in patients with R/R FL. Better understanding of the immune biology of this disease may facilitate the development of effective checkpoint-based strategies. This trial was registered at www.clinicaltrials.gov as #NCT02038946.
AB - Nivolumab, an anti-programmed death-1 (PD-1) monoclonal antibody, showed promising activity in relapsed or refractory (R/R) follicular lymphoma (FL) in a phase 1 study. We conducted a phase 2 trial to further evaluate its efficacy and safety in patients with R/R FL and to explore biomarkers of response. Patients with R/R FL and at least 2 prior lines of therapy, each containing a CD20 antibody or an alkylating agent, were treated with nivolumab 3 mg/kg every 2 weeks. The primary end point was objective response rate (ORR) assessed by an independent radiologic review committee. Biomarker analyses included gene expression profiling and multiplex immunofluorescence studies of pretreatment tumor samples. A total of 92 patients were treated. After a minimum follow-up of 12 months, ORR was 4% (4 of 92 patients). Median progression-free survival (PFS) was 2.2 months (95% confidence interval [CI], 1.9-3.6 months). Median duration of response was 11 months (95% CI, 8-14 months). Exploratory analyses suggested that responders had significantly higher proportion of CD3+ T cells in the tumor microenvironment than nonresponders, but no significant differences in PD-1 or programmed death-ligand 1 expression were observed. High expression of a set of tumor-associated macrophage genes was associated with reduced PFS (hazard ratio, 3.28; 95% CI, 1.76-6.11; P = .001). The safety profile was consistent with previous reports of nivolumab. In conclusion, nivolumab monotherapy was associated with very limited activity in patients with R/R FL. Better understanding of the immune biology of this disease may facilitate the development of effective checkpoint-based strategies. This trial was registered at www.clinicaltrials.gov as #NCT02038946.
U2 - 10.1182/blood.2019004753
DO - 10.1182/blood.2019004753
M3 - Article
C2 - 32870269
AN - SCOPUS:85096684938
SN - 0006-4971
VL - 137
SP - 637
EP - 645
JO - Blood
JF - Blood
IS - 5
ER -
