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

Philippe Armand, Andreas Engert, Anas Younes, Michelle Fanale, Armando Santoro, Pier Luigi Zinzani, John M. Timmerman, Graham P. Collins, Radhakrishnan Ramchandren, Jonathon B. Cohen, Jan Paul De Boer, John Kuruvilla, Kerry J. Savage, Marek Trneny, Margaret A. Shipp, Kazunobu Kato, Anne Sumbul, Benedetto Farsaci, Stephen Maxted Ansell

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1428-1439
Number of pages12
JournalJournal of Clinical Oncology
Volume36
Issue number14
DOIs
StatePublished - May 10 2018

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Cell Transplantation
Hodgkin Disease
Disease Progression
Safety
Advisory Committees
Neutropenia
Tumor Burden
Drug-Related Side Effects and Adverse Reactions
Treatment Failure
Lipase
Radiology
Disease-Free Survival
Therapeutics
History
nivolumab
Ligands
cAC10-vcMMAE

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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. / Armand, Philippe; Engert, Andreas; Younes, Anas; Fanale, Michelle; Santoro, Armando; Zinzani, Pier Luigi; Timmerman, John M.; Collins, Graham P.; Ramchandren, Radhakrishnan; Cohen, Jonathon B.; De Boer, Jan Paul; Kuruvilla, John; Savage, Kerry J.; Trneny, Marek; Shipp, Margaret A.; Kato, Kazunobu; Sumbul, Anne; Farsaci, Benedetto; Ansell, Stephen Maxted.

In: Journal of Clinical Oncology, Vol. 36, No. 14, 10.05.2018, p. 1428-1439.

Research output: Contribution to journalArticle

Armand, P, Engert, A, Younes, A, Fanale, M, Santoro, A, Zinzani, PL, Timmerman, JM, Collins, GP, Ramchandren, R, Cohen, JB, De Boer, JP, Kuruvilla, J, Savage, KJ, Trneny, M, Shipp, MA, Kato, K, Sumbul, A, Farsaci, B & Ansell, SM 2018, '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', Journal of Clinical Oncology, vol. 36, no. 14, pp. 1428-1439. https://doi.org/10.1200/JCO.2017.76.0793
Armand, Philippe ; Engert, Andreas ; Younes, Anas ; Fanale, Michelle ; Santoro, Armando ; Zinzani, Pier Luigi ; Timmerman, John M. ; Collins, Graham P. ; Ramchandren, Radhakrishnan ; Cohen, Jonathon B. ; De Boer, Jan Paul ; Kuruvilla, John ; Savage, Kerry J. ; Trneny, Marek ; Shipp, Margaret A. ; Kato, Kazunobu ; Sumbul, Anne ; Farsaci, Benedetto ; Ansell, Stephen Maxted. / 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. In: Journal of Clinical Oncology. 2018 ; Vol. 36, No. 14. pp. 1428-1439.
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title = "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",
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)–na{\"i}ve (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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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 Maxted

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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