Pembrolizumab in relapsed or refractory Hodgkin lymphoma: 2-year follow-up of KEYNOTE-087

Abstract

Programmed death-1 inhibitors are approved for patients with relapsed or refractory classic Hodgkin lymphoma (RRcHL). We present the 2-year follow-up of the phase 2 KEYNOTE-087 study of pembrolizumab in 210 patients, based on HL progression after autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (BV; cohort 1); salvage chemotherapy and BV, with ineligibility for SCT owing to chemorefractory disease (cohort 2); and progression after SCT without BV (cohort 3). With a median follow-up of 27.6 months, the objective response rate (ORR) by blinded independent central review was 71.9% (95% CI, 65.3-77.9), the complete response rate (CRR) was 27.6%, and the partial response (PR) rate was 44.3%. Median duration of response was 16.5 months (range, 0.0+ to 27.0+ [+, no progressive disease at last assessment]) in all patients, 22.1 months in cohort 1, 11.1 months in cohort 2, and 24.4 months in cohort 3. Median progression-free survival was not reached in all patients with CR: 13.8 months (95% CI, 12.0-22.1) for patients with PR and 10.9 months (95% CI, 5.6-11.1) for patients with stable disease. Median overall survival was not reached in all patients or in any cohort. Treatment-related adverse events (TRAEs) of any grade occurred in 153 (72.9%) patients; grades 3 and 4 occurred in 25 (12.0%) patients; none resulted in death. Results confirmed effective antitumor activity, durability of response, and manageable safety of pembrolizumab monotherapy in RRcHL, regardless of prior treatment and including chemoresistant cHL. This trial was registered at www.clinicaltrials.gov as #NCT02453594.

Conflict of interest statement

Conflict-of-interest disclosure: R.C. reports employment, a leadership position, or an advisory role at Seattle Genetics, Pharmacyclics, Merck & Co, Inc, Genentech, Inc, and Millennium Pharmaceuticals, Inc; honoraria from Seattle Genetics; research funding from Merck & Co, Inc, Bristol-Myers Squibb, Seattle Genetics, Millennium Pharmaceuticals, Inc, and Pharmacyclics. P.L.Z. reports consulting for Verstem, Merck & Co, Inc, Eusapharma, and Sanofi; speaker fees from Verastem, Celltrion, Gilead, Janssen-Cilag, Bristol-Myers Squibb, Servier, Merck & Co, Inc, Immune Design, Celgene, Portola, Roche, Eusapharma, and Kyowa Kirin; and advisory board fees from Verastem, Celltrion, Gilead, Janssen-Cilag, Bristol-Myers Squibb, Servier, Sandoz, Merck & Co, Inc, Immune Design, Celgene, Portola, Roche, Eusapharma, and Kyowa Kirin. P.A. reports employment, a leadership position, or an advisory role at Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc, Kenilworth, NJ, Bristol-Myers Squibb, and Infinity Pharmaceuticals; research funding from Merck & Co, Inc, Bristol-Myers Squibb, Pfizer, Inc, Affimed, Roche, Serventa, Otsuka, and Sigma-Tau; and travel fees, gifts, and other compensation from Bristol-Myers Squibb and Merck & Co, Inc. N.A.J. reports employment, a leadership position, or an advisory role at Roche, AbbVie, Inc, and Lundbeck; honoraria from Roche, AbbVie, Inc, Lundbeck, and Seattle Genetics; research funding from Roche, AbbVie, Inc, and Lundbeck; and travel fees, gifts, and other compensation from Roche and Lundbeck. P.B. reports honoraria from Takeda France, and Bristol-Myers Squibb; consulting and advisory roles at Takeda France; and research funding from Millennium and Takeda. J.R. reports employment, a leadership position, or an advisory role at Takeda Pharmaceutical Company, Seattle Genetics, and Novartis; stock ownership or options from GlaxoSmithKline and AstraZeneca; and research funding from Takeda Pharmaceutical Company. V.R. reports honoraria from Infinity Pharmaceuticals, Bristol-Myers Squibb, Eisai, PharmaMar, and Gilead Sciences; consulting or advisory roles for Infinity Pharmaceuticals, PharmaMar, Gilead Sciences, NanoString Technologies, Incyte, Bristol-Myers Squibb, Merck & Co, Inc, Roche/Genentech, Epizyme, AstraZeneca, and Immune Design; research funding from Argenx BVBA; patents, royalties, and other intellectual property regarding trial BAY1000394 for mantle cell lymphoma; expert testimony for Servier; travel, accommodations and expenses from Roche, Bristol-Myers Squibb, and AstraZeneca; and service as principal or subinvestigator of clinical trials for AbbVie, Agios Pharmaceuticals, Amgen, Argenx BVBA, Arno Therapeutics, Astex Pharmaceuticals, AstraZeneca, Aveo, Bayer Healthcare AG, BBB Technology, BV, Blueprint Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene Corporation, Chugai Pharmaceutical Co, Clovis Oncology, Daiichi Sankyo, Debiopharm, SA, Eisai, Eli Lilly, Exelixis, Forma, Gamamabs, Genentech, Inc, GlaxoSmithKline, H3 Biomedicine, Inc, Hoffmann-La Roche AG, Innate Pharma, Iris Servier, Janssen Cilag, Kyowa Kirin Pharmaceutical Development, Inc, Loxo Oncology, Lytix Biopharma AS, Medimmune, Menarini Ricerche, Merck Sharp & Dohme, Chibret, Merrimack Pharmaceuticals, Merus, Millennium Pharmaceuticals, Nanobiotix, Nektar Therapeutics, Novartis Pharmaceuticals, Octimet Oncology, NV, Oncoethix, Onyx Therapeutics, Orion Pharma, Oryzon Genomics, Pfizer, Inc, Pharma Mar, Pierre Fabre, Roche, Sanofi Aventis, Taiho Pharma, Tesaro, Inc, and Xencor. V.R. also reports the following to his institution: as part of the Drug Development Department (DITEP): principal or subinvestigator of clinical trials for AbbVie, Aduro Biotech, Agios Pharmaceuticals, Amgen, Argenx, BVBA, Arno Therapeutics, Astex Pharmaceuticals, AstraZeneca, AstraZeneca, AB, Aveo, Bayer Healthcare, AG, Bbb Technologies, BV, Beigene, Bioalliance Pharma, Biontech AG, Blueprint Medicines, Boehringer Ingelheim, Boston Pharmaceuticals, Inc, Bristol-Myers Squibb, Bristol-Myers Squibb International Corporation, Celgene Corporation, Cephalon, Chugai Pharmaceutical Co, Clovis Oncology, Daiichi Sankyo, Debiopharm, SA, Eisai, Eli Lilly, Exelixis, Forma, Gamamabs, Genentech, Inc, Gilead Sciences, Inc, GlaxoSmithKline, Glenmark Pharmaceuticals, H3 Biomedicine, Inc, Hoffmann-La Roche, AG, Incyte Corporation, Innate Pharma, Institut de Recherche Pierre Fabre, Iris Servier, Janssen-Cilag, Janssen Research Foundation, Kura Oncology, Kyowa Kirin Pharmaceutical Development, Inc, Lilly France, Loxo Oncology, Lytix Biopharma, AS, Medimmune, Menarini Ricerche, Merck KGaA, Merck Sharp & Dohme, Chibret, Merrimack Pharmaceuticals, Merus, Millennium Pharmaceuticals, Nanobiotix, Nektar Therapeutics, Nerviano Medical Sciences, Novartis Pharmaceuticals, Octimet Oncology NV, Oncoethix, Oncomed, Oncopeptides, Onyx Therapeutics, Orion Pharma, Oryzon Genomics, Pfizer, Inc, Pharma Mar, Pierre Fabre Medicament, Plexxikon, Rigontec, GmbH, Roche, Sanofi Aventis, Sierra Oncology, Taiho Pharma, Tesaro, Tioma Therapeutics, Wyeth Pharmaceuticals France, Xencor, and Y’s Therapeutics; research grants from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Janssen-Cilag, Merck & Co, Inc, Novartis, Pfizer, Inc, Roche, and Sanofi; and nonfinancial support (drug supplied) from AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Johnson & Johnson, Eli Lilly, Medimmune, Merck & Co, Inc, NH TherAGuiX, Pfizer, Inc, and Roche. D.M. reports honoraria from Roche Holding AG, Merck & Co, Inc, Bristol-Myers Squibb, and Takeda Pharmaceutical Company. T.P.V. reports employment, a leadership position, or an advisory role at Roche, Takeda Pharmaceutical Company, Genesis Pharmaceutical, Inc, Novartis, and Bristol-Myers Squibb; honoraria from Roche, Takeda Pharmaceutical Company, Novartis, and Bristol-Myers Squibb; and travel fees, gifts, and other compensation from Roche, Takeda Pharmaceutical Company, and Genesis Pharmaceutical, Inc. B.v.T. reports other compensation from Novartis, Takeda Pharmaceutical Company, Amgen, Celgene, and Merck Sharp & Dohme Corp. M.A.S. reports employment, a leadership position, or an advisory role at AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme Corp, Gilead Sciences, Inc, and Takeda Pharmaceutical Company; honoraria from AstraZeneca, Bristol-Myers Squibb, Merck & Co, Inc, Gilead Sciences, Inc, and Takeda Pharmaceutical Company; and research funding from Bristol-Myers Squibb and Bayer. J.L., E.K. and A.N. report employment at Merck Sharp & Dohme Corp. A.B. reports employment, a leadership position, or an advisory role at Merck Sharp & Dohme Corp and stock ownership in Merck Sharp & Dohme Corp and Amgen. C.H.M. reports employment, a leadership position, or an advisory role at Celgene, Genentech, Inc, Merck Sharp & Dohme Corp, and Seattle Genetics; and research funding from Pharmacyclics, Genentech, Inc, Merck & Co, and Seattle Genetics. H.J.L. and A.T. declare no competing financial interests.

© 2019 by The American Society of Hematology.

Figures

Graphical abstract

Figure 1.

Kaplan-Meier estimate of duration of response. Responders by cohort (A) and by best response (B). *Based on Kaplan-Meier estimate.

Figure 2.

Kaplan-Meier estimate of PFS. In all patients and by cohort (A) and patients with complete or PR in all patients (B), cohort 1 (C), cohort 2 (D), and cohort 3 (E). *Based on Kaplan-Meier method for censored data.

Figure 3.

Kaplan-Meier estimate of overall survival, in all patients and by cohort.

Figure 4.

Duration of response in first course and second course in patients treated with a second pembrolizumab course. Patient 10 discontinued the second course because of an adverse event.