Nivolumab for Relapsed/Refractory Classic Hodgkin Lymphoma After Failure of Autologous Hematopoietic Cell Transplantation: Extended Follow-Up of the Multicohort Single-Arm Phase II CheckMate 205 Trial

• Type of Material: Article
• Authors: Philippe Armand, Dana-Farber Cancer Institute; Andreas Engert, University Hospital of Cologne; Anas Younes, Memorial Sloan Kettering Cancer Center; Michelle Fanale, University of Texas; Armando Santoro, Humanitas University; Pier Luigi Zinzani, University of Bologna; John M. Timmerman, University of California Los Angeles; Graham P. Collins, Churchill Hospital; Radhakrishnan Ramchandren, Barbara Ann Karmanos Cancer Institute; Jonathon B Cohen, Emory University; Jan Paul De Boer, Antoni van Leeuwenhoek Hospital; John Kuruvilla, University of Toronto; Kerry J. Savage, BC Cancer Agency; Marek Trneny, Charles University; Margaret A. Shipp, Dana-Farber Cancer Institute; Kazunobu Kato, Bristol Myers Squibb; Anne Sumbul, Bristol Myers Squibb; Benedetto Farsaci, Bristol Myers Squibb; Stephen M. Ansell, Mayo Clinic
• Language: English
• Date: 2018-05-10
• Publisher: American Society of Clinical Oncology
• Publication Version: Final Published Version
• Copyright Statement: © 2018 by American Society of Clinical Oncology
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1200/JCO.2017.76.0793
• Title of Journal or Parent Work: Journal of Clinical Oncology
• ISSN: 0732-183X
• Volume: 36
• Issue: 14
• Start Page: 1428
• End Page: +
• Grant/Funding Information: Supported by Bristol-Myers Squibb, which also funded medical writing support.; Writing assistance, in the form of writing the first draft, drafting tables, and collating author comments, was provided by Matthew Thomas, at Caudex, under the direction of the authors, and was funded by Bristol-Myers Squibb.; P.A. acknowledges support from the Harold and Virginia Lash Foundation.; J.B.C. acknowledges support from the American Society of Hematology and Lymphoma Research Foundation (388017).; M.T. acknowledges support from Charles University (Q28 - 206028-9). M.A.S. acknowledges support from the US National Institutes of Health (R01CA161026) and the Miller Fund.; G.P.C. acknowledges support from the Blood Theme of the National Institute for Health Research Oxford Biomedical Research Centre and Cancer Research UK Experimental Cancer Medicines Centre.; Editorial assistance was also provided by Stephanie Wolfe (Caudex), funded by Bristol-Myers Squibb.
• Keywords: PD-1 BLOCKADE; PEMBROLIZUMAB; GEMCITABINE; EFFICACY; ACTIVATION; SOLID TUMORS; Life Sciences & Biomedicine; Science & Technology; BRENTUXIMAB VEDOTIN; Oncology; LIGAND; OUTCOMES; RESPONSE CRITERIA
• Research Categories: Health Sciences, Oncology

Abstract

Purpose Genetic alterations causing overexpression of programmed death-1 ligands are near universal in classic Hodgkin lymphoma (cHL). Nivolumab, a programmed death-1 checkpoint inhibitor, demonstrated efficacy in relapsed/refractory cHL after autologous hematopoietic cell transplantation (auto-HCT) in initial analyses of one of three cohorts from the CheckMate 205 study of nivolumab for cHL. Here, we assess safety and efficacy after extended follow-up of all three cohorts. Methods This multicenter, single-arm, phase II study enrolled patients with relapsed/refractory cHL after auto-HCT treatment failure into cohorts by treatment history: brentuximab vedotin (BV)–naïve (cohort A), BV received after auto-HCT (cohort B), and BV received before and/or after auto-HCT (cohort C). All patients received nivolumab 3 mg/kg every 2 weeks until disease progression/unacceptable toxicity. The primary end point was objective response rate per independent radiology review committee. Results Overall, 243 patients were treated; 63 in cohort A, 80 in cohort B, and 100 in cohort C. After a median follow-up of 18 months, 40% continued to receive treatment. The objective response rate was 69% (95% CI, 63% to 75%) overall and 65% to 73% in each cohort. Overall, the median duration of response was 16.6 months (95% CI, 13.2 to 20.3 months), and median progression-free survival was 14.7 months (95% CI, 11.3 to 18.5 months). Of 70 patients treated past conventional disease progression, 61% of those evaluable had stable or further reduced target tumor burdens. The most common grade 3 to 4 drug-related adverse events were lipase increases (5%), neutropenia (3%), and ALT increases (3%). Twenty-nine deaths occurred; none were considered treatment related. Conclusion With extended follow-up, responses to nivolumab were frequent and durable. Nivolumab seems to be associated with a favorable safety profile and long-term benefits across a broad spectrum of patients with relapsed/refractory cHL.