Idecabtagene Vicleucel (Ide-cel) in Patients (Pts) with Newly Diagnosed Multiple Myeloma (NDMM) with an Inadequate Response to Front-Line Autologous Stem Cell Transplantation (ASCT): KarMMa-2 Cohort 2c Extended Follow-up

Introduction

Induction therapy (Tx) followed by ASCT and lenalidomide (LEN) maintenance is the standard of care in transplant-eligible pts with NDMM. Pts who have suboptimal response after front-line ASCT, however, have an increased risk of progression or death. Ide-cel demonstrated significantly improved median progression-free survival (PFS) and overall response rate (ORR) vs standard regimens in KarMMa-3 in pts with early-line triple-class-exposed relapsed and refractory multiple myeloma (MM). KarMMa-2 (NCT03601078) is a multicohort, phase 2, multicenter trial evaluating the efficacy and safety of ide-cel in several MM disease settings; cohort 2c includes pts with NDMM who achieved < very good partial response (VGPR) after front-line ASCT. An extended follow-up analysis (median follow-up of 39.4 months) of cohort 2c was presented at ASH 2023 (Dhodapkar M, et al. ASH 2023; P2101). Here, we report results with 55.4 months of median follow-up and additional data on pts who received LEN maintenance at the investigator's discretion.

Methods

Adult pts with NDMM who received ≥ 3 cycles of induction Tx (proteasome inhibitor, immunomodulatory agent, dexamethasone), and had < VGPR 70-110 days after ASCT (single/tandem) were eligible. Pts received a single ide-cel infusion (150-450 × 10⁶ chimeric antigen receptor-positive T cells) and could receive maintenance Tx post-infusion at investigator discretion. The primary endpoint was complete response rate (CRR); secondary endpoints included ORR, duration of response (DOR), PFS, overall survival (OS), safety, cellular kinetics, and patient-reported outcomes on health-related quality of life (HRQoL). Minimal residual disease (MRD) negativity (sensitivity, 10^-5), an exploratory endpoint, is also reported.

Results

At data cutoff (June 28, 2024), with a median follow-up of 55.4 (range, 51.4-59.5) months, all 31 pts treated with ide-cel were alive; 28 (90.3%) remained in follow-up and 3 (9.7%) discontinued due to disease progression or withdrawal by pt. Eight pts received LEN maintenance after ide-cel at the investigator's discretion. Among all 31 ide-cel-treated pts, CRR and ORR were 80.6% and 87.1%, respectively. Among the 8 pts who received LEN maintenance, CRR and ORR were 75.0% and 100.0%, respectively. Median DOR, PFS, and OS were not reached; 36-month event-free rates were 81.5%, 76.8%, and 100.0%, respectively. Of the 8 pts who received LEN maintenance after ide-cel infusion, none experienced disease progression. At 36 months, MRD negativity was confirmed in 12/18 (66.7%) evaluable pts; all 12 achieved ≥ CR. Since last data cutoff, 1 pt with MRD-negative MM changed to MRD-positive at 36 months, and 1 pt who had previously achieved MRD negativity was indeterminate at 36 months. Among the 6 evaluable pts who received LEN maintenance, 3/6 (50.0%) achieved MRD negativity at 36 months. There were no new safety signals nor reports of parkinsonism or Guillain-Barré syndrome since the previous data cutoff. In the 8 pts who received LEN maintenance, 6 (75.0%) experienced grade 3/4 AE, most commonly neutropenia, and 1 (12.5%) experienced grade 3/4 infection on or after LEN maintenance. All 8 pts were still receiving LEN at data cutoff. Robust CAR+ T cell expansion was observed in 31 pts, with higher expansion in pts with ≥ CR vs < CR.

Following ide-cel treatment, HRQoL improved and disease symptoms were stable over time (assessed by European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Core Questionnaire and EORTC Quality of Life Multiple Myeloma Module 20 Questionnaire). More than 75% of pts had improved or stable global health status/QoL by month 3.

Conclusions

With extended follow-up, ide-cel continued to demonstrate deep, durable responses in pts with < VGPR to front-line ASCT. No new safety signals were observed and no deaths were reported. Data in a small group of pts in cohort 2c showed that ide-cel followed by LEN maintenance extended disease control. Pts who received LEN maintenance did not experience disease progression regardless of MRD status. Stable or improved HRQoL was observed after ide-cel treatment. Overall, ide-cel continued to show a favorable clinical benefit-risk profile in NDMM after ASCT. The phase 3 KarMMa-9 study (NCT06045806), currently recruiting, will compare ide-cel followed by LEN maintenance vs LEN maintenance alone in pts with NDMM after suboptimal response to ASCT.

Paul:Johnson & Johnson: Membership on an entity's Board of Directors or advisory committees; Regeneron Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Research Funding; AbbVie Inc: Membership on an entity's Board of Directors or advisory committees. Dhodapkar:Janssen: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Lava Therapeutics: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees. Alsina:Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: 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. Berdeja:Janssen: Speakers Bureau; AstraZeneca, Bristol Myers Squibb, Caribou, Galapagos, Janssen, K36, Kite Pharma, Legend Biotech, Pfizer, Regeneron, Roche, Sanofi, Sebia, Takeda: Consultancy; 2 Seventy Bio, Abbvie, Amgen, BMS, C4 Therapeutics, Caribou Biosciences, CARsgen, Cartesian Therapeutics, Celularity, CRISPR Therapeutics, Fate Therapeutics, Genentech, GSK, Ichnos Sciences, Incyte, Janssen, Juno Therapeutics, K36 Therapeutics. Karyopharm: Research Funding. Richard:Heidelberg Pharma: Research Funding; C4 Therapeutics: Research Funding; Gracell Therapeutics: Other: Steering Committee, Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Steering Committee, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Vij:Sanofi, BMS, Takeda: Other, Patents & Royalties; Janssen, Pfizer, GSK, Regeneron, Karyopharm: Other, Patents & Royalties. Leleu:Kite, A Gilead Company: Consultancy, Honoraria. Bergsagel:Oncopeptides: Consultancy; Pfizer: Research Funding; Omeros: Consultancy; Cellcentric: Consultancy; Janssen: Consultancy; Sanofi: Research Funding; BMS/Celgene: Research Funding; Novartis: Research Funding. Reshef:TScan: Consultancy, Research Funding; TCR2: Research Funding; Sanofi: Research Funding; Atara Biotherapeutics: Research Funding; Immatics: Research Funding; Takeda: Research Funding; BMS: Research Funding; Abbvie: Research Funding; Sana Biotechnology: Consultancy; CareDx: Research Funding; Cabaletta: Research Funding; Synthekine: Research Funding; Gilead Sciences: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Quell Biotherapeutics: Consultancy; Orca Bio: Consultancy; Autolus: Consultancy; Bayer: Consultancy; J&J: Research Funding; Genentech: Research Funding; Allogene: Consultancy; Precision Biosciences: Research Funding. Usmani:Merck: Research Funding; Pharmacyclics: Research Funding; SecuraBio: Consultancy; Bristol-Myers Squibb - Celgene:: Consultancy, Research Funding; Bristol-Myers Squibb - Celgene: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding; EdoPharma: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Sanofi: Consultancy, Research Funding; Genentech: Consultancy; Gilead: Research Funding; Pfizer: Consultancy; Sanofi: Consultancy, Research Funding; Array Biopharma: Research Funding; Amgen: Consultancy, Research Funding; TeneoBio: Consultancy; Gracell: Consultancy; SeaGen: Consultancy, Research Funding; Oncopeptides: Consultancy; Takeda: Consultancy, Research Funding; SkylineDX: Consultancy, Research Funding; GSK: Consultancy, Research Funding; Johnson & Johnson - Janssen: Consultancy, Research Funding. Truppel-Hartmann:2seventy bio: Current Employment, Current equity holder in publicly-traded company. Basudhar:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties: PCT/US2023/078557 - Filed: November 2, 2023. Thompson:BMS: Current Employment. Wu: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. Eliason:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Park:Bristol Myers Squibb: Current Employment. Tran:Bristol Myers Squibb: Current Employment. Chaudhry:Bristol Myers Squibb: Current Employment. Siegel:Merck: Honoraria; Envision Pharma: Honoraria; Sanofi: Honoraria; Prothena: Honoraria; Sebia: Honoraria; Roche: Honoraria; K36 Therapeutics: Honoraria; Pfizer: Honoraria; COTA: Current holder of stock options in a privately-held company; Envision Pharma: Honoraria; BMS: Honoraria. Patel:BMS: Consultancy, Other: chair of scientific advisory board ; Abbvie: Consultancy; Caribou Sciences: Consultancy; Sanofi: Consultancy; Takeda: Consultancy; AstraZeneca: Consultancy; Kite, A Gilead company: Consultancy, Other: scientific advisory board; Merck: Consultancy; Johnson & Johnson (Janssen): Consultancy; Pfizer: Consultancy; Genentech: Consultancy; Poseida: Consultancy; Oricel: Consultancy, Other: Chair of scientific board.