Five-year follow-up of KEYNOTE-087: pembrolizumab monotherapy for relapsed/refractory classical Hodgkin lymphoma

Philippe Armand, Pier Luigi Zinzani, Hun Ju Lee, Nathalie A Johnson, Pauline Brice, John Radford, Vincent Ribrag, Daniel Molin, Theodoros P Vassilakopoulos, Akihiro Tomita, Bastian von Tresckow, Margaret A Shipp, Alex F Herrera, Jianxin Lin, Eunhee Kim, Samhita Chakraborty, Patricia Marinello, Craig H Moskowitz, Philippe Armand, Pier Luigi Zinzani, Hun Ju Lee, Nathalie A Johnson, Pauline Brice, John Radford, Vincent Ribrag, Daniel Molin, Theodoros P Vassilakopoulos, Akihiro Tomita, Bastian von Tresckow, Margaret A Shipp, Alex F Herrera, Jianxin Lin, Eunhee Kim, Samhita Chakraborty, Patricia Marinello, Craig H Moskowitz

Abstract

Previous analyses of the phase 2 KEYNOTE-087 (NCT02453594) trial of pembrolizumab monotherapy demonstrated effective antitumor activity with acceptable safety in patients with relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL). However, long-term response durability and outcome of patients who receive a second course after treatment discontinuation after complete response (CR) remain of clinical interest. We present KEYNOTE-087 data after >5 years of median follow-up. Patients with R/R cHL and progressive disease (PD) after autologous stem cell transplantation (ASCT) and brentuximab vedotin (BV; cohort 1), salvage chemotherapy and BV without ASCT (cohort 2), or ASCT without subsequent BV (cohort 3), received pembrolizumab for ≤2 years. Patients in CR who discontinued treatment and subsequently experienced PD were eligible for second-course pembrolizumab. Primary end points were the objective response rate (ORR) using blinded central review and safety. The median follow-up was 63.7 months. ORR was 71.4% (95% confidence interval [CI], 64.8-77.4; CR, 27.6%; partial response, 43.8%). Median duration of response (DOR) was 16.6 months; median progression-free survival was 13.7 months. A quarter of responders, including half of complete responders, maintained a response for ≥4 years. Median overall survival was not achieved. Among 20 patients receiving second-course pembrolizumab, ORR for 19 evaluable patients was 73.7% (95% CI, 48.8-90.8); median DOR was 15.2 months. Any-grade treatment-related adverse events occurred in 72.9% of patients and grade 3 or 4 adverse events occurred in 12.9% of patients; no treatment-related deaths occurred. Single-agent pembrolizumab can induce durable responses, particularly in patients achieving CR. Second-course pembrolizumab frequently reinduced sustained responses after relapse from initial CR.

Conflict of interest statement

Conflict-of-interest disclosure: P.A. reports grants or contracts to his institution from Merck, BMS, Adaptive, Genentech, IGM, and AstraZeneca within the last 24 months and Affimed, Tensha, Otsuka, and Sigma Tau; research funding from Kite within the last 24 months; consulting fees from Merck, BMS, ADC Therapeutics, GenMab, Enterome, Genentech/Roche, ATB Therapeutics, and Foresight within the last 24 months and from Pfizer, Affimed, Infinity, ADC Therapeutics, Celgene, Morphosys, Daiichi Sankyo, Miltenyi, Tessa, GenMab, C4, Enterome, Regeneron, Epizyme, and AstraZeneca; and honoraria from Merck and BMS. P.L.Z. reports honoraria from Roche, Takeda, Gilead, Sanofi, Incyte, Novartis, Merck, BMS, AstraZeneca, and Kyowa Kirin. H.J.L. reports grants or contracts from BMS, Seagen, Oncternal, Merck, and Takeda; consulting fees from Century Therapeutics; and honoraria from Aptitude Health and the Korean Society of Cardio-Oncology. N.A.J. reports consulting fees from Merck, AbbVie, BeiGene, Roche, BMS, and Kite; and honoraria from Roche, AbbVie, and BeiGene. V.R. reports advisory board roles with Gilead, Infinity, MSD, BMS, Nanostring, Incyte, Roche, and AstraZeneca; and research funding from Astex, Argen-X, and GSK. D.M. reports honoraria from MSD and BMS. T.P.V. reports grants or contracts from Merck, Takeda, Amgen, Pfizer, and Dr Reddy’s; consulting fees from Takeda, Roche, Genesis Pharma, and Novartis; honoraria from Takeda, Roche, Genesis Pharma, Merck, Novartis, Amgen, GSK, AbbVie, Integris, and AstraZeneca; and stock or stock options in Merck. A.T. reports grants or contracts from Chugai Pharmaceutical, Kyowa Kirin, Perseus Proteomics, Pfizer Japan, and Novartis Pharma K.K.; and honoraria from Chugai Pharmaceutical, Takeda Pharmaceutical, Nippon Shinyaku, Ono Pharmaceutical, and Eisai. B.v.T. reports grants or contracts from Novartis, Takeda, and Merck Sharp & Dohme; consulting fees from Allogene, BMS/Celgene, Cerus, Incyte, Miltenyi, Novartis, Pentixafarm, Roche, Amgen, Pfizer, Takeda, Merck Sharp & Dohme, and Gilead Kite; honoraria from AstraZeneca, Novartis, Roche Pharma AG, Takeda, and Merck Sharp & Dohme; and support for attending meetings and/or travel from AbbVie, AstraZeneca, Kite-Gilead, Merck Sharp & Dohme, Takeda, and Novartis. M.A.S. reports grants or contracts from BMS, Bayer, AbbVie, and AstraZeneca; and consulting fees from AstraZeneca. A.F.H. reports grants or contracts from BMS, Genentech, Merck, Seattle Genetics, AstraZeneca, Karyopharm, Kite Pharma, Gilead Sciences, AstraZeneca, and ADC Therapeutics; and consulting fees from BMS, Genentech, Merck, Seattle Genetics, AstraZeneca, Karyopharm, ADC Therapeutics, Takeda, Tubulis, Regeneron, Genmab, and Pfizer. J.L. reports employment at Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ, and is a share/stockholder or has stock options in Merck & Co Inc, Rahway, NJ. E.K. reports employment at Merck Sharp & Dohme LLC, a subsidiary of Merck & Co Inc, Rahway, NJ, at the time of this analysis. S.C. reports employment at Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ, and is a share/stockholder or has stock options in Merck & Co Inc, Rahway, NJ. P.M. reports employment at Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ, and is a share/stockholder or has stock options in Merck & Co, Inc, Rahway, NJ. C.H.M. reports research funding from Merck & Co, Inc. The remaining authors declare no competing financial interests.

© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

Figures

Graphical abstract
Graphical abstract
Figure 1.
Figure 1.
ORR per IWG 2007 and Lugano 2014 criteria for the overall population and by cohort. NA, not assessed; SD, stable disease.
Figure 2.
Figure 2.
Kaplan-Meier estimates for the overall population and by cohort. (A) Response duration; (B) PFS; (C) OS.
Figure 3.
Figure 3.
Kaplan-Meier estimates for the overall population based on the best objective response. (A) Response duration; (B) PFS; (C) OS.
Figure 4.
Figure 4.
Kaplan-Meier estimates for patients who received second-course treatment. (A) Duration of the second response; (B) PFS; (C) OS.

References

    1. Chen R, Zinzani PL, Fanale MA, et al. Phase II study of the efficacy and safety of pembrolizumab for relapsed/refractory classic hodgkin lymphoma. J Clin Oncol. 2017;35(19):2125–2132.
    1. Chen R, Zinzani PL, Lee HJ, et al. Pembrolizumab in relapsed or refractory Hodgkin lymphoma: 2-year follow-up of KEYNOTE-087. Blood. 2019;134(14):1144–1153.
    1. Armand P, Engert A, Younes A, et al. 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. J Clin Oncol. 2018;36(14):1428–1439.
    1. Armand P, Kuruvilla J, Michot JM, et al. KEYNOTE-013 4-year follow-up of pembrolizumab in classical Hodgkin lymphoma after brentuximab vedotin failure. Blood Adv. 2020;4(12):2617–2622.
    1. Hoppe RT, Advani RH, Ai WZ, et al. NCCN Guidelines® insights: Hodgkin lymphoma, version 2.2022. J Natl Compr Canc Netw. 2022;20(4):322–334.
    1. Keytruda (pembrolizumab) injection, for intravenous use. Merck Sharp & Dohme LLC; Prescribing information: 2023.
    1. Cheson BD. The International Harmonization Project for response criteria in lymphoma clinical trials. Hematol Oncol Clin North Am. 2007;21(5):841–854.
    1. Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014;32(27):3059–3068.
    1. Zinzani PL, Chen R, Armand P, et al. Pembrolizumab monotherapy in patients with primary refractory classical Hodgkin lymphoma who relapsed after salvage autologous stem cell transplantation and/or brentuximab vedotin therapy: KEYNOTE-087 subgroup analysis. Leuk Lymphoma. 2020;61(4):950–954.
    1. Kuruvilla J, Ramchandren R, Santoro A, et al. Pembrolizumab versus brentuximab vedotin in relapsed or refractory classical Hodgkin lymphoma (KEYNOTE-204): an interim analysis of a multicentre, randomised, open-label, phase 3 study. Lancet Oncol. 2021;22(4):512–524.
    1. Merryman RW, Castagna L, Giordano L, et al. Allogeneic transplantation after PD-1 blockade for classic Hodgkin lymphoma. Leukemia. 2021;35(9):2672–2683.
    1. Ansell SM, Bröckelmann PJ, von Keudell G, et al. Nivolumab for relapsed or refractory (R/R) classical Hodgkin lymphoma (CHL) after autologous transplantation: 5-year overall survival from the phase 2 CheckMate 205 study. Hematol Oncol. 2021;39(suppl 2):122–125.

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere