Efficacy and safety results from CheckMate 140, a phase 2 study of nivolumab for relapsed/refractory follicular lymphoma
Efficacy and safety results from CheckMate 140, a phase 2 study of nivolumab for relapsed/refractory follicular lymphoma
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.
637-645
Armand, Philippe
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Janssens, Ann
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Gritti, Giuseppe
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Radford, John
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Timmerman, John
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Pinto, Antonio
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Mercadal Vilchez, Santiago
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Johnson, Peter
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Cunningham, David
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Leonard, John P
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Rodig, Scott J
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Martín-Regueira, Patricia
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Sumbul, Anne
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Samakoglu, Selda
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Tang, Hao
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Ansell, Stephen M
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4 February 2021
Armand, Philippe
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Janssens, Ann
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Gritti, Giuseppe
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Radford, John
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Timmerman, John
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Pinto, Antonio
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Mercadal Vilchez, Santiago
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Johnson, Peter
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Cunningham, David
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Leonard, John P
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Rodig, Scott J
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Martín-Regueira, Patricia
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Sumbul, Anne
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Samakoglu, Selda
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Tang, Hao
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Ansell, Stephen M
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Armand, Philippe, Janssens, Ann, Gritti, Giuseppe, Radford, John, Timmerman, John, Pinto, Antonio, Mercadal Vilchez, Santiago, Johnson, Peter, Cunningham, David, Leonard, John P, Rodig, Scott J, Martín-Regueira, Patricia, Sumbul, Anne, Samakoglu, Selda, Tang, Hao and Ansell, Stephen M
(2021)
Efficacy and safety results from CheckMate 140, a phase 2 study of nivolumab for relapsed/refractory follicular lymphoma.
Blood, 137 (5), .
(doi:10.1182/blood.2019004753).
Abstract
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.
Text
CM140 FL manuscript for Blood - Submitted July 1
- Accepted Manuscript
More information
Accepted/In Press date: 13 July 2020
e-pub ahead of print date: 31 August 2020
Published date: 4 February 2021
Additional Information:
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
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Local EPrints ID: 448471
URI: http://eprints.soton.ac.uk/id/eprint/448471
ISSN: 0006-4971
PURE UUID: d5ef9826-36e7-4107-83c0-23cb31b2cab3
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Date deposited: 22 Apr 2021 16:47
Last modified: 17 Mar 2024 06:28
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Contributors
Author:
Philippe Armand
Author:
Ann Janssens
Author:
Giuseppe Gritti
Author:
John Radford
Author:
John Timmerman
Author:
Antonio Pinto
Author:
Santiago Mercadal Vilchez
Author:
Peter Johnson
Author:
David Cunningham
Author:
John P Leonard
Author:
Scott J Rodig
Author:
Patricia Martín-Regueira
Author:
Anne Sumbul
Author:
Selda Samakoglu
Author:
Hao Tang
Author:
Stephen M Ansell
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