P-069: Idecabtagene vicleucel (ide-cel) in patients (pts) with triple-class–exposed (TCE) relapsed and refractory multiple myeloma (RRMM): the 5-year follow-up analysis from KarMMa

Introduction: Pts with RRMM have poor survival outcomes once they become TCE to immunomodulatory agents, proteasome inhibitors, and anti-CD38 mAbs. In a prior analysis (median follow-up: 24.8 mo) of the KarMMa trial (NCT03361748), in pts with TCE RRMM who received ≥3 prior lines of treatment (LoTs), treatment (tx) with ide-cel resulted in deep, durable responses (ORR 73%, median DOR [mDOR] 10.9 mo, median PFS [mPFS] 8.6 mo, and median OS [mOS] 24.8 mo; Anderson. ASCO 2021). Correlative analysis showed that lower soluble BCMA (sBCMA) levels at infusion were associated with better outcomes (Rytlewski. ASCO 2022). In the phase 3 KarMMa-3 trial (NCT03651128), ide‑cel significantly improved mPFS and ORR vs standard regimens (Rodríguez-Otero. NEJM 2023) in pts with TCE RRMM who received 2–4 prior LoTs. The KarMMa 5-y median follow-up analysis is presented here.

Methods: Pts with heavily pretreated RRMM who were TCE and had disease refractory to the last tx received a single infusion of ide-cel at a dose range of 150−450×10⁶ CAR+ T cells. Primary endpoint: ORR. Key secondary endpoint: complete response rate (CRR). Other secondary endpoints: PFS, OS, DOR, and safety.

Results: Of 149 pts enrolled, 137 pts who received ide-cel infusion were included in this analysis, including 9 pts from the Japanese cohort. At a median follow-up of 63.6 mo (range 48.4−70.5; data cutoff Dec 20, 2023), ORR was 76.6% (95%CI 69.6−83.7), CRR was 34.3% (95%CI 26.4−42.3), and mDOR was 11.3 mo (range 10.0−12.6). mPFS was 10.8 mo (95%CI 6.1−11.9); mOS was 28.2 mo (20.2–38.1). A subset of pts (n=9; 6.6%) who attained a stringent complete response (sCR; n=7), CR (n=1), and very good partial response (n=1) with a single infusion of ide-cel were still in remission at this data cutoff (DOR: 48.8−64.9 mo) despite being heavily pretreated and having high-risk features. Seventy-six (55.5%) pts received ≥1 subsequent anti-MM tx and had PFS2 of 15.2 mo (95%CI 12.8–18.7). Ide‑cel safety profile was consistent with prior reports; no new safety signals were observed. No long-term investigator-identified neurotoxicity, Guillain−Barré syndrome, or parkinsonism events were reported. Incidence rate (% per 100 pt‑y, 95%CI) of second primary malignancies (SPMs) was 3.7 (2.0−6.9). Hematologic SPMs were observed in 3 pts (2 myelodysplastic syndrome, 1 plasmablastic lymphoma); none were T-cell related. The strongest correlate of prolonged PFS was lower pre-infusion sBCMA level, which is an indicator of tumor burden.

Conclusions:
In this 5-y median follow-up analysis of the KarMMa trial, a single infusion of ide-cel continued to show deep and durable responses in pts with TCE RRMM. The correlation of lower pre‑infusion sBCMA levels with better PFS highlights the need for managing tumor burden before ide-cel tx. Safety profile of ide‑cel was consistent with previous reports; no new safety signals observed. This analysis supports the use of ide‑cel in TCE RRMM to achieve long-term survival outcomes with a favorable safety profile.