Brentuximab vedotin, nivolumab, doxorubicin, and dacarbazine for advanced-stage classical Hodgkin lymphoma
- PMID: 39622165
- DOI: 10.1182/blood.2024024681
Brentuximab vedotin, nivolumab, doxorubicin, and dacarbazine for advanced-stage classical Hodgkin lymphoma
Abstract
Treatment options for stage I/II bulky and advanced-stage disease have recently extensively changed. For decades in North America, ABVD (doxorubicin hydrochloride [Adriamycin], bleomycin sulfate, vinblastine sulfate, and dacarbazine) has been a frontline standard-of-care option for patients with advanced classical Hodgkin lymphoma (cHL). Recent data on combining brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine demonstrated improved overall survival compared with ABVD but increased adverse events (AEs). We hypothesized that replacing vinblastine with nivolumab (brentuximab vedotin and nivolumab [AN] + doxorubicin and dacarbazine [AD]; AN+AD) may improve efficacy and safety. This phase 2, open-label multipart, multicenter study enrolled patients with treatment-naive stage II bulky or III/IV cHL. Patients received ≤6 cycles of AN+AD; granulocyte-colony stimulating factor (G-CSF) prophylaxis was optional, per institutional guidelines. At the time of planned analysis (N = 57), complete response (CR) and objective response rates were 88% (95% confidence interval [CI], 76.3-94.9) and 93% (95% CI, 83.0-98.1), respectively. With a median follow-up of 24.2 months (95% CI, 23.4-26.9), the 2-year progression-free survival rate was 88% (95% CI, 75.7-94.6); 88% (95% CI, 75.7-94.6) had a response lasting >2 years. Most common grade ≥3 treatment-related AEs were alanine aminotransferase increased (11%) and neutropenia (9%); 44% had treatment-related peripheral sensory neuropathy (grade 1/2, 40%; grade 3, 4%). No febrile neutropenia occurred; 49% received G-CSF prophylaxis. AN+AD led to a high CR rate and favorable safety profile. Further evaluation of programmed death receptor 1 inhibitor and CD30 antibody-drug conjugate combination regimens in frontline advanced-stage cHL is warranted. This trial was registered at www.clinicaltrials.gov as #NCT03646123 and www.clinicaltrialsregister.eu as #EudraCT 2020-004027-17.
Conflict of interest statement
Conflict-of-interest disclosure: H.J.L. serves as a consultant to Century Therapeutics; received honoraria from Aptitude Health, Cancer Experts, Curio Sciences, Deloitte, Guidepoint, Janssen, Korean Society of Cardiology, and Olson Research; and reports research funding/grants from Bristol Myers Squibb (BMS), Celgene, Oncternal Therapeutics, Pharmacyclics, Seagen (acquired by Pfizer in December 2023), and Takeda. R.R. serves as a consultant to BMS, Merck, Pharmacyclics, and Seagen (acquired by Pfizer in December 2023) and reports research funding/grants from Merck, Pharmacyclics, Seagen (acquired by Pfizer in December 2023), Curis, Trillium, and Cellectar. J.F. reports stock ownership in Amgen, Abbott, and AbbVie and serves on a speakers bureau for Jazz Pharmaceuticals and AstraZeneca. J.M. serves on a speakers bureau for AstraZeneca and Janssen. I.W.F. serves as a consultant for AbbVie, BeiGene, Genentech, Genmab, Kite Pharma, Roche, and Vincerx Pharma; reports research grants from AbbVie, Acerta Pharma, Agios, ArQule, AstraZeneca, BeiGene, Biopath, BMS, Calibr, CALGB, Celgene, City of Hope National Medical Center, Constellation Pharmaceuticals, Curis, CTI Biopharma, Epizyme, Fate Therapeutics, Forma Therapeutics, Forty Seven, Genentech, Gilead Sciences, InnoCare Pharma, IGM Biosciences, Incyte, Infinity Pharmaceuticals, Janssen, Kite Pharma, Loxo, Marker Therapeutics, Merck, Millennium Pharmaceuticals, MorphoSys, Myeloid Therapeutics, Novartis, Nurix, Pfizer, Pharmacyclics, Portola Pharmaceuticals, Rhizen Pharmaceuticals, Roche, Seattle Genetics, Step Pharma, Tessa Therapeutics, TG Therapeutics, Trillium Therapeutics, Triphase Research and Development Corporation, Unum Therapeutics, Verastem, Vincerx Pharma, and 2seventy bio; and serves on an advisory committee for Vincerx. J.M.B. serves on a speakers bureau for BioGene; is a consultant to AbbVie, Adaptive Biotechnologies, ADC Therapeutics (ADCT), AstraZeneca, BeiGene, BMS, Constellation, Eli Lilly, Foresight, Genentech, Genmab, Kura, Kymera, MorphoSys, Novartis, Nurix, Regeneron, Seagen (acquired by Pfizer in December 2023), and TG Therapeutics; and reports research funding/grants from MorphoSys. Y.L. serves as an advisory board member for Pfizer, AbbVie, Spectrum, Genmab, TG Therapeutics, Seagen (acquired by Pfizer in December 2023), BeiGene, Gilead, BMS, and Genentech; is a consultant to Pfizer; serves on the speakers bureau for Kyowa; and reports research funding/grants from BeiGene, ADCT, Genentech, and Seagen (acquired by Pfizer in December 2023). M.P. was previously employed at Brooke Army Medical Center. M.R. serves as an advisory board member for AstraZeneca, Alexion, Sanofi Genzyme, BMS, ADCT, GlaxoSmithKline (GSK), Adaptive, Epizyme, Agios, PharmaEssentia, Takeda, and BeiGene; is a consultant to Takeda, Sanofi Genzyme, and GSK; serves on a speakers bureau for Takeda, AstraZeneca, AbbVie, Alexion, Epizyme, Ipsen, Astellas, Incyte/MorphoSys, BeiGene, ADCT, Sanofi, Adaptive, CTI, GSK, Genmab, and BMS; reports research funding/grants from Amgen, Genentech, Seagen (acquired by Pfizer in December 2023), Merck, Janssen, AstraZeneca, AbbVie, Sanofi Genzyme, Novartis, GSK, Epizyme, Karyopharm, and MorphoSys. R.C. serves as an advisory board member for AbbVie, AstraZeneca, Daiichi Sankyo, BMS, Kite Pharmaceuticals, MorphoSys, Janssen, Pfizer, Biotheranostics, and GSK and received honoraria from Curio Sciences, Amerisource Bergen, Cardinal health, and MJH Life Sciences. T.A.F. serves as an advisory board member for BMS, Seagen (acquired by Pfizer in December 2023), Genmab, and AstraZeneca; reports travel expenses from AbbVie, Kite Pharma, Seagen (acquired by Pfizer in December 2023), and Takeda; serves as a consultant to AstraZeneca, BMS, MorphoSys, and Seagen (acquired by Pfizer in December 2023); serves on a speakers bureau for AbbVie and Seagen (acquired by Pfizer in December 2023); reports research funding and grants from Amgen, BMS, Celgene, Cell Medica, Corvus, Eisai, Kyowa Hakko Kirin, Pfizer, Portola Pharma, Roche, Seagen (acquired by Pfizer in December 2023), Trillium, and Viracta; and received honoraria from AbbVie, BMS, Kite Pharma, Pharmacyclics, Seagen (acquired by Pfizer in December 2023), Takeda, and Genmab. H.Y. serves on a speakers bureau for AbbVie, AstraZeneca, BeiGene, GlaxoSmithKline, Janssen Biotech, Karyopharm Therapeutics, and Takeda. M.I.-O. serves as an advisory board member for ADCT, Kite, Jansen Biotech, and Incyte. A.P. serves on an advisory board for Janssen and AbbVie. L.M. serves on a speakers bureau for Incyte and Taiho Oncology; and serves on the scientific advisory board for Pfizer. A.D. serves on a speakers bureau for Janssen/Pharmacyclics, AVEO, Lilly, Seagen (acquired by Pfizer in December 2023), and Astellas. V.R. received honoraria from MJH Holdings and Curio Sciences. M.D.G. serves as an advisory board member for Janssen Oncology and Sanofi. J.R. serves as an advisory board member for Genentech; serves on a speakers bureau for Amgen, AbbVie, Karyopharm, AstraZeneca, and BeiGene; reports employment at Texas Oncology; and serves as a consultant to Seagen (acquired by Pfizer in December 2023), Novocure, AADI, and AbbVie. L.H., M.A.F., and W.G. report equity ownership and employment for Pfizer, Inc. C.A.Y. serves on a speakers bureau for BeiGene and as a consultant to Seagen (acquired by Pfizer in December 2023) and reports research funding/grants from Seagen (acquired by Pfizer in December 2023). P.G. declares no competing financial interests.
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