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denotes that this is a recommended PHD Trainee Session.
denotes that this is a ticketed session.Session: 704. Cellular Immunotherapies: Early Phase and Investigational Therapies: Poster I
Patients (pts) with multiple myeloma (MM) have a higher risk of progression/death following an inadequate response to frontline ASCT (van de Velde Eur J Haematol 2017). Therapies (Tx) with novel mechanisms of action may further improve response outcomes. Ide-cel previously demonstrated frequent, deep, and durable responses in KarMMa (Munshi N Engl J Med 2021) and significantly improved median progression-free survival (PFS) and overall response rate (ORR) versus standard regimens in KarMMa-3 (Rodríguez-Otero N Engl J Med 2023) in pts with triple-class–exposed relapsed and refractory MM. KarMMa-2 (NCT03601078) is a multicohort, phase 2, multicenter trial evaluating the efficacy and safety of ide-cel in pts with MM; cohort 2c included pts with NDMM who had an inadequate response to frontline Tx with ASCT. In cohort 2c, with a median follow-up of 27.9 months, ide-cel demonstrated deep and durable responses; complete response (CR) rate was 74.2% (ORR, 87.1%), with a 24-month PFS rate of 83.1% (Dhodapkar Blood 2022). Here, we report results with an additional 11.5 months of median follow-up for updated efficacy and safety data, and health-related quality of life (HRQoL) outcomes in cohort 2c.
Methods
Eligible pts had NDMM, received ≥ 3 cycles of induction Tx (including a proteasome inhibitor, an immunomodulatory agent, and dexamethasone), had < very good partial response (VGPR) 70–110 days after ASCT (single/tandem), and had Eastern Cooperative Oncology Group performance status ≤ 1. Pts received a single infusion of ide-cel (dose range: 150–450 × 106 CAR+ T cells) after lymphodepletion and could receive maintenance Tx post-infusion at investigator’s discretion. The primary endpoint CR rate and secondary endpoints ORR, duration of response (DOR), PFS, overall survival (OS), safety, and patient-reported outcomes on HRQoL, assessed via European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core 30 Questionnaire (QLQ-C30) and EORTC Quality of Life Multiple Myeloma Module 20 Questionnaire (QLQ-MY20), are reported. The exploratory endpoint of minimal residual disease (MRD) negativity (sensitivity, 10-5) is also reported.
Results
At data cutoff (May 3, 2023), with a median follow-up of 39.4 (range, 31.6–44.7) months, all 31 pts who were infused with ide-cel were alive; 28 (90.3%) remained in follow-up, with 3 (9.7%) having discontinued due to disease progression. The ORR and CR rates were 87.1% and 77.4%, respectively (Table); best overall response in 1 pt improved from VGPR to stringent CR. The median DOR was not reached (NR; 95% CI, NR–NR), neither was median PFS (95% CI, 38.0–NR) or median OS (95% CI, NR–NR); the 36-month event-free rates were 80.9%, 76.8%, and 100.0%, respectively. In pts who did not receive lenalidomide (LEN) maintenance, 9 (29.0%) had disease progression; of the 8 pts who received LEN maintenance post ide-cel infusion, none experienced disease progression. At 36 months, MRD negativity was confirmed in 9/14 (64.3%) evaluable pts; all 9 achieved ≥ CR.
In this extended follow-up, safety results were generally consistent with the previous data cutoff. All pts experienced ≥ 1 any-grade adverse event (AE), most commonly hematologic, including neutropenia (80.6%), anemia (38.7%), leukopenia (32.3%), and thrombocytopenia (29.0%); infection and infestation AEs occurred in 74.2% of pts. No grade 5 AEs were reported. Incidence of any-grade cytokine release syndrome (58.1%; no grade ≥ 3) was unchanged and there were no additional reports of parkinsonism since the previous report.
Overall, HRQoL improved (Figure) and MM disease symptoms were stable over time based on the EORTC QLQ-C30 and QLQ-MY20, respectively, following ide-cel treatment; by month 3, > 75% of pts had improved or stable global health status/QoL.
Conclusions
Ide-cel continued to demonstrate deep, durable responses in pts with an inadequate response to frontline ASCT, no new safety signals were observed with extended follow-up, and no deaths were reported. No pts who received LEN maintenance post ide-cel experienced disease progression. Ide-cel treatment resulted in stable or improved HRQoL. Overall, ide-cel continued to demonstrate a favorable clinical benefit–risk profile in NDMM after ASCT.
Study support
2seventy bio and Celgene, a Bristol-Myers Squibb Company.
Disclosures: Dhodapkar: Sanofi: Membership on an entity's Board of Directors or advisory committees; Lava Therapeutics: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees. Alsina: Janssen Oncology: Consultancy, Speakers Bureau; Genzyme: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Research Funding; RevHealth LLC, Red Med LLC: Honoraria. Berdeja: 2seventy bio: Consultancy, Research Funding; Acetylon: Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Sanofi: Research Funding; Poseida: Research Funding; Novartis: Research Funding; Lilly: Research Funding; Legend Biotech: Consultancy; 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; Roche: Consultancy; Teva: Research Funding. Patel: 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; 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; Takeda: Consultancy. Richard: Bristol Myers Squibb: Honoraria; C4 Therapeutics: Research Funding; Heidelberg Pharma: Research Funding; Janssen: Honoraria. Vij: Bristol Myers Squibb: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Janssen: Honoraria; Harpoon: Honoraria; Karyopharm: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria, Research Funding; Legend: Honoraria. Leleu: Takeda: Honoraria; Novartis: Honoraria; Sanofi: Honoraria; Merck: Honoraria; AbbVie: Honoraria; Harpoon Therapeutics: Honoraria; GSK: Honoraria; Amgen: Honoraria; Janssen: Honoraria; BMS/Celgene: Honoraria. Bergsagel: CellCentric: Consultancy; Salarius: Consultancy; Janssen: Consultancy; Pfizer: Research Funding; Aptitude Health: Honoraria; Novartis: Patents & Royalties: Royalty for hCRBN mice; Mayo Clinic: Patents & Royalties: Royalty for hCRBN and Vk*MYC mice; Radmetrix: Consultancy; Omeros: Consultancy. Reshef: Gilead Sciences: Consultancy, Honoraria, Other: Travel support, Research Funding; Bristol Myers Squibb: Honoraria, Research Funding; Atara Biotherapeutics: Consultancy, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Research Funding; Synthekine: Consultancy, Research Funding; Orca: Consultancy; MidaTech: Consultancy; Capstan: Consultancy; Jasper: Consultancy; J&J: Research Funding; Precision Biosciences: Research Funding; Bayer: Consultancy; Regeneron: Consultancy; TScan: Consultancy, Research Funding; CareDx: Research Funding; Instil Bio: Consultancy; Allogene: Consultancy; Quell Biotherapeutics: Consultancy; Sanofi: Research Funding; Immatics: Research Funding; TCR2: Research Funding. Usmani: Novartis: Membership on an entity's Board of Directors or advisory committees; EdoPharma: Membership on an entity's Board of Directors or advisory committees; K36 Therapeutics: Membership on an entity's Board of Directors or advisory committees; Merck: Research Funding; Pharmacyclics: Research Funding; Array Biopharma: Research Funding; TeneoBio: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; SkylineDX: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead Sciences: Membership on an entity's Board of Directors or advisory committees, Research Funding; SecuraBio: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Moderna: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Meyer Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees, Research Funding. Truppel-Hartmann: 2seventy bio: Current Employment. Basudhar: Bristol Myers Squibb, IOCT-TRC: Current Employment. Thompson: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Zheng: Bristol Myers Squibb: Current Employment; Janssen: Ended employment in the past 24 months. Eliason: GlaxoSmith-Kline: Ended employment in the past 24 months; Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Zhong: Bristol Myers Squibb: Current Employment. Greggio: Bristol Myers Squibb: Current Employment. Tran: Bristol Myers Squibb: Current Employment. Chaudhry: Bristol Myers Squibb: Current Employment. Carrasco-Alfonso: Bristol Myers Squibb: Current Employment; Kyverna Therapeutics: Ended employment in the past 24 months; Achilles Therapeutics: Other: Holder of stock options in a privately-held company in the past 36 months. Siegel: Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celularity Scientific: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.
OffLabel Disclosure: Ide-cel is currently approved for the treatment of patients with relapsed/refractory multiple myeloma who have received 3 or more prior treatments. Here, ide-cel efficacy and safety was explored in the newly diagnosed setting (inadequate response to frontline ASCT) in a phase 2 clinical trial.
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