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J Clin Oncol. 2016 Aug 10;34(23):2698-704. doi: 10.1200/JCO.2015.65.9789. Epub 2016 Jun 6.

Nivolumab in Patients With Relapsed or Refractory Hematologic Malignancy: Preliminary Results of a Phase Ib Study.

Author information

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.

PMID:
27269947
PMCID:
PMC5019749
DOI:
10.1200/JCO.2015.65.9789
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Authors’ disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article.

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