TY - JOUR
T1 - Nivolumab for relapsed/refractory classic hodgkin lymphoma after failure of autologous hematopoietic cell transplantation
T2 - Extended follow-up of the multicohort single-arm phase II checkmate 205 trial
AU - Armand, Philippe
AU - Engert, Andreas
AU - Younes, Anas
AU - Fanale, Michelle
AU - Santoro, Armando
AU - Zinzani, Pier Luigi
AU - Timmerman, John M.
AU - Collins, Graham P.
AU - Ramchandren, Radhakrishnan
AU - Cohen, Jonathon B.
AU - De Boer, Jan Paul
AU - Kuruvilla, John
AU - Savage, Kerry J.
AU - Trneny, Marek
AU - Shipp, Margaret A.
AU - Kato, Kazunobu
AU - Sumbul, Anne
AU - Farsaci, Benedetto
AU - Ansell, Stephen M.
N1 - Funding Information:
Supported by Bristol-Myers Squibb, which also funded medical writing support. The views expressed in this article are the authors’ own and not an official position of Bristol-Myers Squibb or their respective institutions. P.A. acknowledges support from the Harold and Virginia Lash Foundation. 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. 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. The authors thank all co-investigators and the patients and families who participated in the trial. 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. Editorial assistance was also provided by Stephanie Wolfe (Caudex), funded by Bristol-Myers Squibb.
Funding Information:
On the basis of encouraging initial data, nivolumab was approved by the US Food and Drug Administration for the treatment of adults with cHL that has relapsed/progressed after auto-HCTand BV treatment or three or more prior lines of systemic therapy including auto-HCT,12 and by the European Medicines Agency for the treatment of adults with relapsed/refractory cHL after auto-HCT and BV.19 The efficacy of PD-1 blockade in relapsed/refractory cHL was further supported by positive results in a recent phase II study of pem-brolizumab.20 This extended analysis of three CheckMate 205 cohorts confirms the favorable safety profile of nivolumab in relapsed/refractory cHL. After the 18-month follow-up, safety outcomes remained consistent with previous reports, and most events were G1 or G2. In addition, nivolumab led to frequent and durable responses, including in patients naïve to BV, patients who received BV at differing times relative to auto-HCT, and patients refractory to prior lines of therapy.
Publisher Copyright:
© 2018 by American Society of Clinical Oncology.
PY - 2018/5/10
Y1 - 2018/5/10
N2 - 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.
AB - 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.
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U2 - 10.1200/JCO.2017.76.0793
DO - 10.1200/JCO.2017.76.0793
M3 - Article
C2 - 29584546
AN - SCOPUS:85045947562
VL - 36
SP - 1428
EP - 1439
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
SN - 0732-183X
IS - 14
ER -