Nivolumab in patients with relapsed or refractory hematologic malignancy: Preliminary results of a phase Ib study Journal Article

Authors: Lesokhin, A. M.; Ansell, S. M.; Armand, P.; Scott, E. C.; Halwani, A.; Gutierrez, M.; Millenson, M. M.; Cohen, A. D.; Schuster, S. J.; Lebovic, D.; Dhodapkar, M.; Avigan, D.; Chapuy, B.; Ligon, A. H.; Freeman, G. J.; Rodig, S. J.; Cattry, D.; Zhu, L. L.; Grosso, J. F.; Garelik, M. B. B.; Shipp, M. A.; Borrello, I.; Timmerman, J.
Article Title: Nivolumab in patients with relapsed or refractory hematologic malignancy: Preliminary results of a phase Ib study
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. (C) 2016 by American Society of Clinical Oncology
Keywords: ipilimumab; response criteria; antibody; expression; multiple-myeloma; b-cell lymphoma; blockade; advanced melanoma; cancer; b7-h1 pd-l1
Journal Title: Journal of Clinical Oncology
Volume: 34
Issue: 23
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2016-08-10
Start Page: 2698
End Page: 2704
Language: English
ACCESSION: WOS:000382467000005
DOI: 10.1200/jco.2015.65.9789
PMCID: PMC5019749
PUBMED: 27269947
Notes: Article -- Source: Wos
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  1. Alexander Meyer Lesokhin
    106 Lesokhin
  2. Deepika Cattry
    8 Cattry