P-045: Idecabtagene vicleucel (ide-cel) in patients (pts) with clinical high-risk early relapse multiple myeloma (MM) without front-line (1L) autologous stem cell transplantation (ASCT): KarMMA-2 cohort 2B

Introduction: Despite improvements with triplet regimens in 1L MM treatment (tx), pts develop disease refractory to these agents, necessitating txs with novel mechanisms of action. The CAR T cell therapy ide‑cel significantly improved median progression-free survival (mPFS) vs standard regimens in KarMMa-3 in triple‑class–exposed relapsed and refractory MM (RRMM). KarMMa-2 (NCT03601078) is a multicohort, phase 2, multicenter trial of ide‑cel in clinical high-risk MM (early relapse after 1L tx including [cohort 2a] or excluding ASCT [2b] or inadequate response post-1L ASCT [2c]). In cohort 2a (median follow-up, 21.5mo), 24-mo PFS rate was 26% and incidences of grade (gr) 3/4 cytokine release syndrome (CRS) and investigator-identified neurotoxicity (iiNT) were numerically lower vs later tx lines in KarMMa. We report results from KarMMa-2 cohort 2b.

Methods: Adults with disease progression < 18mo post-1L tx (no ASCT; at least IMiD agent, proteasome inhibitor, dexamethasone) received one ide-cel infusion (150–450×10⁶ CAR+ T cells). Primary endpoint: complete response (CR) rate. Secondary endpoints: ORR, duration of response (DOR), PFS, overall survival (OS), safety, pharmacokinetics, health-related quality of life (QOL). Exploratory endpoint: minimal residual disease (MRD) negativity (neg; < 10^-5).

Results: Of 35 enrolled pts, 31 (89%) received ide-cel. At data cutoff (Dec 13, 2023), median follow-up was 30.1 (range 1.0–51.4) mo; 20/31 (65%) pts were ongoing in study and 11 discontinued, mostly due to death (n=7 [23%]; none considered ide-cel-related by investigator). At baseline, median age was 60 (range 32–77) y, 39% of pts had high-risk (HR) cytogenetics, 16% had ultra-HR cytogenetics, 68% had double-class–refractory MM, and 16% had triple-class–refractory MM.
ORR (95% CI) was 94% (79–99). CR rate was 71% (52–86); 16 (52%) pts had ongoing CR. High rates of MRD neg were achieved by evaluable pts with ≥ partial response (12mo, 14/18 [78%]; 24mo, 10/12 [83%]) and with ≥CR (12mo, 13/16 [81%]; 24mo, 9/11 [82%]). Median DOR was not reached (NR); 24mo rate was 65%. Median PFS and OS were NR (PFS rate, 70% at 12mo, 63% at 24mo; OS rate, 90% at 12mo, 79% at 24mo).
Gr 3/4 adverse events (AEs) occurred in 29 (94%) pts, gr 5 AEs in 2 (6%) pts (both MM progression). Gr 3/4 neutropenia and thrombocytopenia occurred in 29 (94%) and 11 (35%) pts, respectively; time to recovery was 1.5 and 2.0mo. Gr 3/4 infections occurred in 6 (19%) pts. CRS occurred in 26 (84%) pts and iiNT in 3 (10%) pts; none were gr ≥3. Robust CAR+ T cell expansion was seen in 31 pts (4.3-fold higher in pts with ≥CR vs < CR [AUC_0–28d]). Pts showed sustained QOL improvement; 75% achieved meaningful improvement by 3mo post-infusion.

Conclusions: In newly diagnosed MM that progressed < 18mo of tx initiation, a single ide-cel infusion demonstrated a favorable benefit–risk profile with frequent, deep, durable responses and a manageable safety profile, consistent with KarMMa-2 cohorts 2a and 2c.
Previously presented at EHA 2024.