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denotes that this is a ticketed session.Type: Oral
Session: 705. Cellular Immunotherapies: Late Phase and Commercially Available Therapies: Cellular Therapy for Multiple Myeloma, B-cell Acute Lymphoblastic Leukemia and B Cell Lymphomas: Clinical Trial and Real World Evidence
Hematology Disease Topics & Pathways:
Research, clinical trials, Biological therapies, adult, Clinical Research, Plasma Cell Disorders, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Diseases, Therapies, Lymphoid Malignancies, Study Population, Human
A single ide-cel infusion showed significantly longer median progression-free survival (PFS) vs std regimens (13.3 vs 4.4 months [mo], HR 0.49, 95% CI 0.38–0.65, P < 0.001) with deep, durable responses in heavily pretreated TCE RRMM at an interim analysis (IA) of KarMMa-3 (NCT03651128); safety data were consistent with prior studies (Rodríguez-Otero et al. NEJM 2023). Ide-cel benefits were consistent across pts in high-risk subgroups and across 2–4 prior lines of therapy (Tx). Results of the preplanned final PFS analysis of KarMMa-3 with 12.3 mo additional follow-up are reported.
Methods
In the phase 3 KarMMa-3 trial, pts with RRMM who received 2–4 prior regimens, including an immunomodulatory agent, proteasome inhibitor, and daratumumab, and were refractory to last regimen were randomized 2:1 to ide-cel or a std regimen (DPd, DVd, IRd, Kd, or EPd). In the ide-cel arm, pts could receive ≤ 1 cycle of optional bridging Tx for disease control. Pts in the std regimens arm could receive ide-cel after confirmed disease progression (PD). The primary endpoint was IRC-assessed PFS in the ITT population; final PFS was planned to be analyzed with ~289 events. Key secondary endpoints were IRC-assessed overall response rate (ORR) and overall survival (OS); other secondary endpoints included complete response rate (CRR), duration of response (DOR), minimal residual disease (MRD) status, time to next anti-myeloma Tx (TTNT; time from randomization to next anti-myeloma Tx [MTx]), event-free survival (EFS; time from randomization to first PD, next MTx or any-cause death, whichever is first), PFS2 (time from randomization to second objective PD or any-cause death, whichever is first), safety, and health-related quality of life (QOL).
Results
Of 386 randomized pts (ide-cel, n = 254; std regimens, n = 132), 225 received ide-cel and 126 received a std regimen. Baseline characteristics were generally balanced. Median follow-up from randomization to data cutoff (April 28, 2023) was 30.9 mo (range 12.7–47.8). Ide-cel significantly improved median PFS (95% CI) vs std regimens (13.8 [11.8–16.1] vs 4.4 [3.4–5.8] mo), representing a 51% reduced risk of PD or death (HR 0.49, 95% CI 0.38–0.63; Figure); 18 mo PFS rates were 41% vs 19%, respectively. Ide-cel significantly improved ORR vs std regimens (71% vs 42%) with deeper (CRR 44% vs 5%; ≥CR and MRD negative status [sensitivity level 10-5], 22% vs 1%), more durable responses (median DOR 16.6 vs 9.7 mo; Table). PFS and ORR benefits of ide-cel vs std regimens were consistent with the IA. Interim OS will be included in the presentation. In pts who received ide-cel (n = 225) or a std regimen (n = 126), median PFS (95% CI) was 15.7 (12.5–18.9) vs 4.4 (3.4–5.8) mo, respectively. In the ITT population, median TTNT, EFS, and PFS2 were numerically longer with ide-cel vs std regimens. Median (range) TTNT was 20.9 (16.6–24.2) vs 7.0 (5.3–8.5) mo. Median (95% CI) EFS was 13.3 (11.3–15.7) vs 3.9 (3.0–5.3) mo. Median PFS2 (95% CI) was 23.5 (18.4–27.9) vs 16.7 (12.2–20.3) mo; ide-cel was next MTx in 70 (53%) pts in the std regimens arm. In the treated population, grade (gr) 3/4 infections occurred in 66/249 (27%) pts in the ide-cel arm vs 25/126 (20%) in the std regimens arm. In the ide-cel safety population, any gr cytokine release syndrome occurred in 197/225 (88%) pts, gr ≥ 3 in 11 (5%); median time to first onset was 1 d (1–14), median duration was 4 d (1–51). Any gr investigator-identified neurotoxicity occurred in 34/225 (15%) pts, gr ≥ 3 in 7 (3%); median time to onset was 3 d (range 1–317); median duration was 2.5 d (range 1–252). Ide-cel continued to demonstrate durable, clinically meaningful improvements in pt-reported outcomes, including symptoms, functioning, and QOL vs std regimens.
Conclusions
In this final PFS analysis of KarMMa-3, significantly longer PFS was maintained with ide-cel; PD or death risk reduced by 51%; responses were deeper and more durable vs std regimens. CRR with ide-cel increased since the IA, indicating a deepening response, but were unchanged with std regimens. A single ide-cel infusion vs continuous treatment with std regimens resulted in longer median TTNT and PFS2, indicating improved long-term disease control. The ide-cel safety profile was consistent with previous reports, with no parkinsonism or Guillain–Barré syndrome reported. These data continue to support use of ide-cel in pts with TCE RRMM.
Study support
2seventy bio and Celgene, a Bristol-Myers Squibb Company.
Disclosures: Rodríguez Otero: Sanofi: Membership on an entity's Board of Directors or advisory committees, Other: Honoraria for lectures; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees, Other: Honoraria for lectures; Amgen: Other: Honoraria for lectures; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Regeneron: Other: Honoraria for lectures; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Honoraria for lectures; Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Honoraria for lectures; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants; Roche: Consultancy. Ailawadhi: AbbVie, Amgen, Ascentage, BMS, Cellectar, GSK, Janssen, Pharmacyclics, Sanofi: Research Funding; Beigene, BMS, Cellectar, GSK, Janssen, Pfizer, Regeneron, Sanofi, Takeda: Consultancy. Arnulf: Bristol Myers Squibb: Consultancy, Honoraria, Other: Meeting travel payments; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Meeting travel payments; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Meeting travel payments; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Meeting travel payments; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Meeting travel payments, Research Funding. Patel: Takeda: Consultancy; AbbVie; Arcellx, AstraZeneca; Bristol Myers Squibb/Celgene Corporation; Caribou Science; Cellectis; Curio Bioscience; Genentech; Janssen Pharmaceuticals, Inc.; Karyopharm; Legend Biotech; Merck & Co., Inc.; Oncopeptides; Pfizer; Precision BioSciences: Consultancy; AbbVie; Allogene Therapeutics, Inc.; Arcellx; Bristol Myers Squibb/Celgene Corporation; Cellectis; Janssen Pharmaceuticals, Inc.; Nektar Therapeutic; Poseida Therapeutics; Precision BioSciences, Inc.; and Takeda Pharmaceuticals U.S.A., Inc.: Research Funding. Cavo: Adaptive: Honoraria; Roche: Honoraria; GlaxoSmithKline: Honoraria; Celgene/Bristol Myers Squibb: Consultancy, Honoraria, Speakers Bureau; Takeda: Honoraria; Amgen: Honoraria; Sanofi: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau. Nooka: Aduro Biotech, Amgen, Arch Oncology, Bristol Myers Squibb, Cellectis, Genentech, GlaxoSmithKline, Janssen, Karyopharm, Kite Pharma, Merck, Pfizer, Takeda: Honoraria, Research Funding; Adaptive Biotechnologies, Amgen, BeyondSpring, Bristol Myers Squibb, Cellectar Biosciences, GlaxoSmithKline, Janssen, Karyopharm, Oncopeptides, ONK therapeutics, Pfizer, Sanofi, Secura Bio, Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Manier: Janssen: Consultancy; BMS: Consultancy; Amgen: Consultancy; Abbvie: Consultancy; Pfizer: Consultancy; Regeneron: Consultancy; Roche: Consultancy; Sanofi: Consultancy. Costa: Adaptive biotechnologies: Consultancy, Honoraria; AbbVie: Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Genentech: Research Funding. Vij: Bristol Myers Squibb: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Legend: Honoraria; Pfizer: Honoraria; Harpoon: Honoraria; Janssen: Honoraria; Karyopharm: Honoraria; Sanofi: Honoraria, Research Funding. Bahlis: Abbvie: Consultancy, Honoraria, Other: member of steering committee; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria; GSK: Consultancy, Other: member of steering committee; Forus: Consultancy, Honoraria; Takeda: Consultancy; Karyopharm therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech/Roche: Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: IRC member and chair, Research Funding. Moreau: janssen, celgene BMS, abbvie, sanofi, amgen, takeda, pfizer: Honoraria, Other: advisory boards; GSK: Honoraria, Other: Advisory Board. Abrahamsen: Janssen: Consultancy, Other: Presentation support; Novartis: Membership on an entity's Board of Directors or advisory committees; Takeda: Other: Presentation support . Baz: Regeneron: Research Funding; GSK: Honoraria; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding; HIKMA Cancer Network: Honoraria; Curio Science: Honoraria; AHOMPR: Honoraria; ASH: Honoraria. Broijl: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees. Chen: Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Other: Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events, Research Funding; Beigene: Membership on an entity's Board of Directors or advisory committees, Other: Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events; Abbvie: Membership on an entity's Board of Directors or advisory committees, Other: Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events; Bristol Myers Squibb: Other: Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events; Gilead Sciences, Inc.: Membership on an entity's Board of Directors or advisory committees, Other: Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events, Research Funding. Jagannath: Bristol Myers Squibb: Consultancy; Janssen: Consultancy; Sanofi: Consultancy; Caribou Biosciences: Consultancy; Takeda: Consultancy; Regeneron: Consultancy; DMC: Membership on an entity's Board of Directors or advisory committees; Mount Sinai Hospital: Current Employment. Raje: Immuneel: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; GlaxoSmithKline: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Caribou Biosciences: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; K36 Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Delforge: Sanofi: Consultancy, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau; Bristol Myers Squibb: Consultancy, Speakers Bureau; Stemline: Consultancy, Speakers Bureau. Iida: Janssen: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Research Funding; Ono: Honoraria, Research Funding; Abbvie: Consultancy, Research Funding; Chugai: Research Funding; Novartis: Consultancy, Research Funding; Otsuka: Research Funding; Amgen: Research Funding; GlaxoSmithKlein: Consultancy, Research Funding; Alexion: Research Funding; Pfizer: Consultancy, Research Funding; Shionogi: Research Funding; Otsuka: Consultancy; Regeneron: Consultancy; Takeda: Consultancy, Honoraria, Research Funding; Bristol-Myers Scuibb: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding. Berdeja: Kite Pharma: Consultancy; Karyopharm: Research Funding; Janssen: Consultancy, Research Funding, Speakers Bureau; Incyte: Research Funding; Ichnos Sciences: Research Funding; GSK: Research Funding; Genentech: Research Funding; Fate Therapeutics: Research Funding; EMD Serono: Research Funding; CRISPR Therapeutics: Consultancy, Research Funding; Celularity: Research Funding; Cartesian: Research Funding; CARsgen: Research Funding; C4 Therapeutics: Research Funding; Celgene: Consultancy, Research Funding; Amgen: Research Funding; AbbVie: Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Acetylon: Research Funding; 2seventy bio: Consultancy, Research Funding; Legend Biotech: Consultancy; Lilly: Research Funding; Novartis: Research Funding; Poseida: Research Funding; Sanofi: Research Funding; Takeda: Consultancy, Research Funding; Roche: Consultancy; Teva: Research Funding. Truppel-Hartmann: 2seventy bio: Current Employment. Bhatnagar: Bristol Myers Squibb: Consultancy; Syneos Health: Current Employment. Wu: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Piasecki: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months, Other: Current holder of stock options in publicly-traded company. Eliason: GlaxoSmith-Kline: Ended employment in the past 24 months; Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Dhanda: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Felten: Bristol Myers Squibb: Current Employment. Caia: Bristol Myers Squibb: Current Employment. Cook: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Popa-McKiver: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Giralt: Amgen, Actinuum, Celgene/BMS, Kite Pharma, Janssen, Jazz Pharmaceuticals, Johnson & Johnson, Novartis, Spectrum Pharma, Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen, Actinuum, Celgene/BMS, Omeros, Johnson & Johnson, Miltenyi, Takeda: Research Funding.
OffLabel Disclosure: In the US, ide-cel is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. The current abstract presents data from the phase 3 KarMMa-3 trial of ide-cel vs standard regimens in patients with RRMM who had received two to four prior regimens and were refractory to the last regimen.