Alexander M Lesokhin1, Stephen M Ansell2, Philippe Armand2, Emma C Scott2, Ahmad Halwani2, Martin Gutierrez2, Michael M Millenson2, Adam D Cohen2, Stephen J Schuster2, Daniel Lebovic2, Madhav Dhodapkar2, David Avigan2, Bjoern Chapuy2, Azra H Ligon2, Gordon J Freeman2, Scott J Rodig2, Deepika Cattry2, Lili Zhu2, Joseph F Grosso2, M Brigid Bradley Garelik2, Margaret A Shipp2, Ivan Borrello2, John Timmerman2. 1. Alexander M. Lesokhin and Deepika Cattry, Memorial Sloan Kettering Cancer Center; Alexander M. Lesokhin, Weill Cornell Medical College, New York, NY; Stephen M. Ansell, Mayo Clinic, Rochester, MN; Philippe Armand, Bjoern Chapuy, Gordon J. Freeman, Scott J. Rodig, and Margaret A. Shipp, Dana-Farber Cancer Institute; David Avigan, Beth Israel Deaconess Medical Center; Azra H. Ligon and Scott J. Rodig, Brigham and Women's Hospital, Boston, MA; Emma C. Scott, Oregon Health & Science University Knight Cancer Institute, Portland, OR; Ahmad Halwani, University of Utah Huntsman Cancer Institute, Salt Lake City, UT; Martin Gutierrez, Hackensack University Medical Center, Hackensack; Lili Zhu, Joseph F. Grosso, and M. Brigid Bradley Garelik, Bristol-Myers Squibb, Princeton, NJ; Michael M. Millenson, Fox Chase Cancer Center; Adam D. Cohen and Stephen J. Schuster, University of Pennsylvania, Philadelphia, PA; Daniel Lebovic, University of Michigan, Ann Arbor, MI; Madhav Dhodapkar, Yale Cancer Center, New Haven, CT; Ivan Borrello, Johns Hopkins University School of Medicine, Baltimore, MD; and John Timmerman, University of California, Los Angeles, CA. lesokhia@mskcc.org. 2. Alexander M. Lesokhin and Deepika Cattry, Memorial Sloan Kettering Cancer Center; Alexander M. Lesokhin, Weill Cornell Medical College, New York, NY; Stephen M. Ansell, Mayo Clinic, Rochester, MN; Philippe Armand, Bjoern Chapuy, Gordon J. Freeman, Scott J. Rodig, and Margaret A. Shipp, Dana-Farber Cancer Institute; David Avigan, Beth Israel Deaconess Medical Center; Azra H. Ligon and Scott J. Rodig, Brigham and Women's Hospital, Boston, MA; Emma C. Scott, Oregon Health & Science University Knight Cancer Institute, Portland, OR; Ahmad Halwani, University of Utah Huntsman Cancer Institute, Salt Lake City, UT; Martin Gutierrez, Hackensack University Medical Center, Hackensack; Lili Zhu, Joseph F. Grosso, and M. Brigid Bradley Garelik, Bristol-Myers Squibb, Princeton, NJ; Michael M. Millenson, Fox Chase Cancer Center; Adam D. Cohen and Stephen J. Schuster, University of Pennsylvania, Philadelphia, PA; Daniel Lebovic, University of Michigan, Ann Arbor, MI; Madhav Dhodapkar, Yale Cancer Center, New Haven, CT; Ivan Borrello, Johns Hopkins University School of Medicine, Baltimore, MD; and John Timmerman, University of California, Los Angeles, CA.
Abstract
PURPOSE: Cancer cells can exploit the programmed death-1 (PD-1) immune checkpoint pathway to avoid immune surveillance by modulating T-lymphocyte activity. In part, this may occur through overexpression of PD-1 and PD-1 pathway ligands (PD-L1 and PD-L2) in the tumor microenvironment. PD-1 blockade has produced significant antitumor activity in solid tumors, and similar evidence has emerged in hematologic malignancies. METHODS: In this phase I, open-label, dose-escalation, cohort-expansion study, patients with relapsed or refractory B-cell lymphoma, T-cell lymphoma, and multiple myeloma received the anti-PD-1 monoclonal antibody nivolumab at doses of 1 or 3 mg/kg every 2 weeks. This study aimed to evaluate the safety and efficacy of nivolumab and to assess PD-L1/PD-L2 locus integrity and protein expression. RESULTS: Eighty-one patients were treated (follicular lymphoma, n = 10; diffuse large B-cell lymphoma, n = 11; other B-cell lymphomas, n = 10; mycosis fungoides, n = 13; peripheral T-cell lymphoma, n = 5; other T-cell lymphomas, n = 5; multiple myeloma, n = 27). Patients had received a median of three (range, one to 12) prior systemic treatments. Drug-related adverse events occurred in 51 (63%) patients, and most were grade 1 or 2. Objective response rates were 40%, 36%, 15%, and 40% among patients with follicular lymphoma, diffuse large B-cell lymphoma, mycosis fungoides, and peripheral T-cell lymphoma, respectively. Median time of follow-up observation was 66.6 weeks (range, 1.6 to 132.0+ weeks). Durations of response in individual patients ranged from 6.0 to 81.6+ weeks. CONCLUSION: Nivolumab was well tolerated and exhibited antitumor activity in extensively pretreated patients with relapsed or refractory B- and T-cell lymphomas. Additional studies of nivolumab in these diseases are ongoing.
PURPOSE: Cancer cells can exploit the programmed death-1 (PD-1) immune checkpoint pathway to avoid immune surveillance by modulating T-lymphocyte activity. In part, this may occur through overexpression of PD-1 and PD-1 pathway ligands (PD-L1 and PD-L2) in the tumor microenvironment. PD-1 blockade has produced significant antitumor activity in solid tumors, and similar evidence has emerged in hematologic malignancies. METHODS: In this phase I, open-label, dose-escalation, cohort-expansion study, patients with relapsed or refractory B-cell lymphoma, T-cell lymphoma, and multiple myeloma received the anti-PD-1 monoclonal antibody nivolumab at doses of 1 or 3 mg/kg every 2 weeks. This study aimed to evaluate the safety and efficacy of nivolumab and to assess PD-L1/PD-L2 locus integrity and protein expression. RESULTS: Eighty-one patients were treated (follicular lymphoma, n = 10; diffuse large B-cell lymphoma, n = 11; other B-cell lymphomas, n = 10; mycosis fungoides, n = 13; peripheral T-cell lymphoma, n = 5; other T-cell lymphomas, n = 5; multiple myeloma, n = 27). Patients had received a median of three (range, one to 12) prior systemic treatments. Drug-related adverse events occurred in 51 (63%) patients, and most were grade 1 or 2. Objective response rates were 40%, 36%, 15%, and 40% among patients with follicular lymphoma, diffuse large B-cell lymphoma, mycosis fungoides, and peripheral T-cell lymphoma, respectively. Median time of follow-up observation was 66.6 weeks (range, 1.6 to 132.0+ weeks). Durations of response in individual patients ranged from 6.0 to 81.6+ weeks. CONCLUSION:Nivolumab was well tolerated and exhibited antitumor activity in extensively pretreated patients with relapsed or refractory B- and T-cell lymphomas. Additional studies of nivolumab in these diseases are ongoing.
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