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.
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. Key Points: • Nivolumab monotherapy was associated with very limited activity in patients with R/R FL. • Understanding the tumor microenvironment may be necessary to develop effective checkpoint-based strategies in FL.
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. Key Points: • Nivolumab monotherapy was associated with very limited activity in patients with R/R FL. • Understanding the tumor microenvironment may be necessary to develop effective checkpoint-based strategies in FL.
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U2 - 10.1182/blood.2019004753
DO - 10.1182/blood.2019004753
M3 - Article
C2 - 32870269
AN - SCOPUS:85096684938
VL - 137
SP - 637
EP - 645
JO - Blood
JF - Blood
SN - 0006-4971
IS - 5
ER -