P866: IDECABTAGENE VICLEUCEL (IDE-CEL) VS STANDARD REGIMENS IN PATIENTS WITH TRIPLE-CLASS–EXPOSED (TCE) RELAPSED AND REFRACTORY MULTIPLE MYELOMA (RRMM): KARMMA-3 SUBGROUP ANALYSIS BY PRIOR LINES OF THERAPY

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Because of earlier use of immunomodulatory (IMiD®) agents, proteasome inhibitors (PIs), and anti-CD38 monoclonal antibody combinations, patients (pts) with RRMM are becoming TCE earlier in their disease course, which represents a therapeutic challenge. In the phase 3 KarMMa-3 trial (NCT03651128), ide-cel, a BCMA-directed CAR T cell therapy, significantly improved median progression-free survival (mPFS, 13.3 vs 4.4 mo; hazard ratio [HR], 0.49; P<0.0001) and overall response rate (ORR, 71% vs 42%; P<0.0001) vs standard (std) regimens in pts with TCE RRMM who received 2–4 prior lines of therapy (LoT). We assessed the consistency of ide-cel benefit vs std regimens across numbers (no.) of prior LoT in pts with TCE RRMM in KarMMa-3. Aims: To compare efficacy and safety of ide-cel vs std regimens by no. of prior LoT in KarMMa-3 pts. Methods: Pts with RRMM who received 2–4 prior LoT, were TCE (IMiD agent, PI, and daratumumab), and had disease refractory to the last regimen were randomized 2:1 to receive ide-cel (target dose range: 150–450 x 106 CAR+ T cells) or a std regimen (DPd, DVd, IRd, Kd, or EPd); randomization stratification factors included no. of prior LoT (2 vs 3 or 4). In this analysis, efficacy and safety were assessed by no. of prior LoT. An analysis was performed to determine the relationship between soluble BCMA (sBCMA) levels and prior LoT. Results: Baseline characteristics were generally balanced between arms across prior LoT subgroups. In both arms, the proportion of pts with triple-class–refractory (TCR) disease increased and median time to progression on last prior therapy decreased from 2 to 4 prior LoT (ide-cel: 50% to 88% and 9.3 to 5.1 mo, respectively). High-risk clinical features were generally balanced across prior LoT in each arm. At a median follow-up of 18.6 (range, 0.4–35.4) mo, PFS improvement for ide-cel vs std regimens was consistent across prior LoT (HR range, 0.45–0.58; Table). In pts with 2 and 3 or 4 prior LoT, mPFS with ide-cel was 15.1 and 12.0 mo, and with std regimens was 4.8 and 4.2 mo, respectively. The 12-mo PFS rates in the ide-cel arm were 64%, 54%, and 46% in pts with 2, 3, and 4 prior LoT, respectively. ORRs and complete response rates (CRRs) were numerically higher with ide-cel vs std regimens regardless of prior LoT. Baseline sBCMA levels were similar in pts with 2 vs 3 or 4 prior LoT in both arms; at nadir, a greater proportion of pts in the ide-cel arm with 2 vs 3 or 4 prior LoT cleared sBCMA level (82% vs 68%; P=0.0238). Proportion of pts who had serious AEs was similar in subgroups by prior LoT (ide-cel, 51–55%; std regimens, 37–39%) and to the overall population (ide-cel, 52%; std regimens, 38%). The safety profile of ide-cel, including cytokine release syndrome (CRS), was similar across prior LoT. Grade 5 CRS occurred in 1 pt each in the 2 and 3 prior LoT subgroups. Investigator-identified neurotoxicity was lowest in pts who had 2 prior LoT (2, 7%; 3 or 4, 19%). Summary/Conclusion: Across prior LoT, the benefit of ide-cel vs std regimens was maintained and the safety profile of ide-cel was consistent. With increasing LoT, pts were more likely to have TCR disease and had numerically poorer efficacy outcomes in both arms. Greater proportion of pts in the ide-cel arm with 2 vs 3 or 4 prior LoT had clearance of tumor burden as measured by sBCMA, raising the possibility of earlier ide-cel use in TCE RRMM.Keywords: Multiple myeloma, CAR-T, Clinical trial, Antigen-specific T cells

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