Phase II Trial of Pembrolizumab Plus Gemcitabine, Vinorelbine, and Liposomal Doxorubicin as Second-Line Therapy for Relapsed or Refractory Classical Hodgkin Lymphoma.

Autor:	Moskowitz AJ; Lymphoma Disease Management Team, Memorial Sloan Kettering Cancer Center, New York, NY., Shah G; Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY., Schöder H; Lymphoma Disease Management Team, Memorial Sloan Kettering Cancer Center, New York, NY., Ganesan N; Lymphoma Disease Management Team, Memorial Sloan Kettering Cancer Center, New York, NY., Drill E; Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY., Hancock H; Lymphoma Disease Management Team, Memorial Sloan Kettering Cancer Center, New York, NY., Davey T; Lymphoma Disease Management Team, Memorial Sloan Kettering Cancer Center, New York, NY., Perez L; Lymphoma Disease Management Team, Memorial Sloan Kettering Cancer Center, New York, NY., Ryu S; Lymphoma Disease Management Team, Memorial Sloan Kettering Cancer Center, New York, NY., Sohail S; Lymphoma Disease Management Team, Memorial Sloan Kettering Cancer Center, New York, NY., Santarosa A; Lymphoma Disease Management Team, Memorial Sloan Kettering Cancer Center, New York, NY., Galasso N; Lymphoma Disease Management Team, Memorial Sloan Kettering Cancer Center, New York, NY., Neuman R; Lymphoma Disease Management Team, Memorial Sloan Kettering Cancer Center, New York, NY., Liotta B; Lymphoma Disease Management Team, Memorial Sloan Kettering Cancer Center, New York, NY., Blouin W; Lymphoma Disease Management Team, Memorial Sloan Kettering Cancer Center, New York, NY., Kumar A; Lymphoma Disease Management Team, Memorial Sloan Kettering Cancer Center, New York, NY., Lahoud O; Lymphoma Disease Management Team, Memorial Sloan Kettering Cancer Center, New York, NY., Batlevi CL; Lymphoma Disease Management Team, Memorial Sloan Kettering Cancer Center, New York, NY., Hamlin P; Lymphoma Disease Management Team, Memorial Sloan Kettering Cancer Center, New York, NY., Straus DJ; Lymphoma Disease Management Team, Memorial Sloan Kettering Cancer Center, New York, NY., Rodriguez-Rivera I; Lymphoma Disease Management Team, Memorial Sloan Kettering Cancer Center, New York, NY., Owens C; Lymphoma Disease Management Team, Memorial Sloan Kettering Cancer Center, New York, NY., Caron P; Lymphoma Disease Management Team, Memorial Sloan Kettering Cancer Center, New York, NY., Intlekofer AM; Lymphoma Disease Management Team, Memorial Sloan Kettering Cancer Center, New York, NY., Hamilton A; Lymphoma Disease Management Team, Memorial Sloan Kettering Cancer Center, New York, NY., Horwitz SM; Lymphoma Disease Management Team, Memorial Sloan Kettering Cancer Center, New York, NY., Falchi L; Lymphoma Disease Management Team, Memorial Sloan Kettering Cancer Center, New York, NY., Joffe E; Lymphoma Disease Management Team, Memorial Sloan Kettering Cancer Center, New York, NY., Johnson W; Lymphoma Disease Management Team, Memorial Sloan Kettering Cancer Center, New York, NY., Lee C; Lymphoma Disease Management Team, Memorial Sloan Kettering Cancer Center, New York, NY., Palomba ML; Lymphoma Disease Management Team, Memorial Sloan Kettering Cancer Center, New York, NY., Noy A; Lymphoma Disease Management Team, Memorial Sloan Kettering Cancer Center, New York, NY., Matasar MJ; Lymphoma Disease Management Team, Memorial Sloan Kettering Cancer Center, New York, NY., Pongas G; Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, FL., Salles G; Lymphoma Disease Management Team, Memorial Sloan Kettering Cancer Center, New York, NY., Vardhana S; Lymphoma Disease Management Team, Memorial Sloan Kettering Cancer Center, New York, NY., Sanin BW; Lymphoma Disease Management Team, Memorial Sloan Kettering Cancer Center, New York, NY., von Keudell G; Lymphoma Disease Management Team, Memorial Sloan Kettering Cancer Center, New York, NY., Yahalom J; Lymphoma Disease Management Team, Memorial Sloan Kettering Cancer Center, New York, NY., Dogan A; Lymphoma Disease Management Team, Memorial Sloan Kettering Cancer Center, New York, NY., Zelenetz AD; Lymphoma Disease Management Team, Memorial Sloan Kettering Cancer Center, New York, NY., Moskowitz CH; Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, FL.
Jazyk:	angličtina
Zdroj:	Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2021 Oct 01; Vol. 39 (28), pp. 3109-3117. Date of Electronic Publication: 2021 Jun 25.
DOI:	10.1200/JCO.21.01056
Abstrakt:	Purpose: We conducted a phase II study evaluating pembrolizumab plus gemcitabine, vinorelbine, and liposomal doxorubicin (pembro-GVD) as second-line therapy for relapsed or refractory (rel/ref) classical Hodgkin lymphoma (cHL) (ClinicalTrials.gov identifier: NCT03618550). Methods: Transplant eligible patients with rel/ref cHL following first-line therapy were treated with two to four cycles of pembrolizumab (200 mg intravenous [IV], day 1), gemcitabine (1,000 mg/m 2 IV, days 1 and 8), vinorelbine (20 mg/m 2 IV, days 1 and 8), and liposomal doxorubicin (15 mg/m 2 , days 1 and 8), given on 21-day cycles. The primary end point was complete response (CR) following up to four cycles of pembro-GVD. Patients who achieved CR by labeled fluorodeoxyglucose-positron emission tomography (Deauville ≤ 3) after two or four cycles proceeded to high-dose therapy and autologous hematopoietic cell transplantation (HDT/AHCT). HDT/AHCT was carried out according to institutional standards, and brentuximab vedotin maintenance was allowed following HDT/AHCT. Results: Of 39 patients enrolled, 41% had primary ref disease and 38% relapsed within 1 year of frontline treatment. 31 patients received two cycles of pembro-GVD, and eight received four cycles. Most adverse events were grade 1 or two, whereas few were grade 3 and included transaminitis (n = 4), neutropenia (n = 4), mucositis (n = 2), thyroiditis (n = 1), and rash (n = 1). Of 38 evaluable patients, overall and CR rates after pembro-GVD were 100% and 95%, respectively. Thirty-six (95%) patients proceeded to HDT/AHCT, two received pre-HDT/AHCT involved site radiation, and 13 (33%) received post-HDT/AHCT brentuximab vedotin maintenance. All 36 transplanted patients are in remission at a median post-transplant follow-up of 13.5 months (range: 2.66-27.06 months). Conclusion: Second-line therapy with pembro-GVD is a highly effective and well-tolerated regimen that can efficiently bridge patients with rel/ref cHL to HDT/AHCT. Competing Interests: Alison J. MoskowitzHonoraria: Seattle GeneticsConsulting or Advisory Role: Seattle Genetics, Takeda, Imbrium Therapeutics, Merck, Janpix, Kyowa Kirin International, miRagen, ADC Therapeutics, Bristol Myers SquibbResearch Funding: Incyte, Seattle Genetics, Merck, Bristol Myers Squibb, miRagen, ADC Therapeutics, BeiGene Gunjan ShahResearch Funding: Janssen, Amgen Anita KumarStock and Other Ownership Interests: BridgebioConsulting or Advisory Role: Celgene, Kite, a Gilead company, AstraZeneca/MedImmuneResearch Funding: AbbVie/Genentech, Adaptive Biotechnologies, Celgene, Seattle Genetics, AstraZeneca/MedImmune, Pharmacyclics Oscar LahoudConsulting or Advisory Role: MorphoSysTravel, Accommodations, Expenses: MorphoSysOpen Payments Link: https://openpaymentsdata.cms.gov/physician/225358/summary Connie L. BatleviStock and Other Ownership Interests: Moderna Therapeutics, Novavax, Pfizer, Bristol Myers Squibb, Regeneron, ViatrisHonoraria: DAVAOncologyConsulting or Advisory Role: Lifesci Capital, GLG, Juno Therapeutics, Celgene, Seattle Genetics, Kite, a Gilead company, TG Therapeutics, Karyopharm TherapeuticsResearch Funding: Janssen Biotech, Novartis, Epizyme, Xynomic Pharma, Bayer, Roche, AutolusOpen Payments Link: https://openpaymentsdata.cms.gov/physician/2778694 Paul HamlinConsulting or Advisory Role: Juno Therapeutics, Karyopharm Therapeutics, Celgene, Sandoz, AstraZeneca/MerckResearch Funding: Spectrum Pharmaceuticals, Seattle Genetics, Janssen, Portola Pharmaceuticals, GlaxoSmithKline, Molecular Templates, Incyte David J. StrausConsulting or Advisory Role: Takeda, Seagen, EpizymeResearch Funding: Takeda Ildefonso Rodriguez-RiveraStock and Other Ownership Interests: Pfizer Philip CaronStock and Other Ownership Interests: AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Johnson & Johnson/Janssen, Novartis, Pfizer, Teva Steven M. HorwitzConsulting or Advisory Role: Celgene, Millennium, Kyowa Hakko Kirin, Seattle Genetics, ADC Therapeutics, Verastem, Takeda, Astex Pharmaceuticals, Kura Oncology, Acrotech Biopharma, C4 Therapeutics, Janssen Oncology, Trillium Therapeutics, Vividion Therapeutics, Myeloid Therapeutics, Ono Pharmaceutical, Secura Bio, Shoreline Biosciences Inc, TubulisResearch Funding: Celgene, Seattle Genetics, Takeda, Kyowa Hakko Kirin, Aileron Therapeutics, ADC Therapeutics, Verastem, 47, Trillium Therapeutics, Daiichi Sankyo, Affimed Therapeutics, Secura Bio Lorenzo FalchiConsulting or Advisory Role: GenmabResearch Funding: Roche, Genmab Erel JoffeConsulting or Advisory Role: AstraZeneca, Epizyme Christina LeeHonoraria: WebMDConsulting or Advisory Role: Intellisphere LLC M. Lia PalombaStock and Other Ownership Interests: Seres TherapeuticsHonoraria: Flagship Biosciences, Evelo Therapeutics, Jazz Pharmaceuticals, Therakos, Amgen, Merck, Seres TherapeuticsConsulting or Advisory Role: Flagship Biosciences, Novartis, Evelo Therapeutics, Jazz Pharmaceuticals, Therakos, Amgen, Merck, Seres Therapeutics, Kite, a Gilead company, Novartis, BeiGeneResearch Funding: Seres TherapeuticsPatents, Royalties, Other Intellectual Property: Intellectual Property Rights, Juno intellectual property rights Ariela NoyConsulting or Advisory Role: MorphoSys, Janssen Biotech, Prime OncologyResearch Funding: Pharmacyclics, Rafael PharmaceuticalsTravel, Accommodations, Expenses: Pharmacyclics, Janssen Oncology Matthew J. MatasarStock and Other Ownership Interests: MerckHonoraria: Genentech, Roche, Bayer, Pharmacyclics, Seattle Genetics, Takeda, Immunovaccine, ADC Therapeutics, Karyopharm TherapeuticsConsulting or Advisory Role: Genentech, Bayer, Merck, Juno Therapeutics, Roche, Teva, Rocket Medical, Seattle Genetics, Daiichi Sankyo, TakedaResearch Funding: Genentech, Roche, GlaxoSmithKline, Bayer, Pharmacyclics, Janssen, Rocket Medical, Seattle Genetics, Immunovaccine, IGM BiosciencesTravel, Accommodations, Expenses: Genentech, Roche, Seattle Genetics, Bayer Georgios PongasHonoraria: Atara Biotherapeutics, Curio Science, OncLive/MJH Life SciencesTravel, Accommodations, Expenses: Atara Biotherapeutics Gilles SallesHonoraria: Roche/Genentech, Janssen, Celgene, Gilead Sciences, Novartis, AbbVie, MorphoSysConsulting or Advisory Role: Roche/Genentech, Gilead Sciences, Janssen, Celgene, Novartis, MorphoSys, Epizyme, Alimera Sciences, Genmab, Debiopharm Group, Velosbio, BMS, BeiGene, Incyte, Miltenyi Biotec, Ipsen Santosha VardhanaHonoraria: AgiosConsulting or Advisory Role: Immunai, ADC Therapeutics Gottfried von KeudelllHonoraria: PharmacyclicsConsulting or Advisory Role: Pharmacyclics, Merck, Incyte Ahmet DoganConsulting or Advisory Role: Seattle Genetics, Takeda, EUSA Pharma, AbbVie, Peerview, Physicans' Education ResourceResearch Funding: Roche/Genentech Andrew D. ZelenetzHonoraria: NCCN, Clinical Care Options, Oncology Information Group, PER, PlexusConsulting or Advisory Role: Gilead Sciences, Amgen, Genentech/Roche, Celgene, AstraZeneca, DAVAOncology, MorphoSys, BeiGene, MEI Pharma, Vaniam Group, Verastem, Pharmacyclics, Karyopharm Therapeutics, Debiopharm Group, Seattle Genetics, Quant Health Ltd, Kite, a Gilead company, Curis, Coherus Biosciences, Juno/Celgene/Bristol Myers Squibb, Curio ScienceResearch Funding: Genentech/Roche, Gilead Sciences, MEI Pharma, BeiGene Craig H. MoskowitzConsulting or Advisory Role: Merck Sharp & Dohme, Molecular Templates, Takeda, AstraZeneca, IncyteResearch Funding: AstraZeneca, Merck Sharp & DohmeNo other potential conflicts of interest were reported.
Databáze:	MEDLINE
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