P-032: Ide-cel versus standard regimens in patients with triple-class–exposed (TCE) relapsed and refractory multiple myeloma (RRMM): a KarMMa-3 analysis in the modified intention to-treat (mITT) population

Introduction: With use of combination regimens, including immunomodulatory (IMiD®) agents, proteasome inhibitors (PI) and daratumumab, patients (pts) with RRMM become TCE earlier in their treatment (tx), which represents an unmet need. In KarMMa-3 (NCT03651128), ide-cel significantly improved median progression-free survival (mPFS 13.3 vs 4.4 mo; HR 0.49; P< 0.001) and overall response rates (ORR 71% vs 42%; P< 0.001) vs standard (std) regimens in pts with TCE RRMM (Rodriguez-Otero, NEJM 2023). Efficacy was analyzed in the KarMMa-3 intent-to-treat (ITT) population (pop). Here, we report outcomes in the mITT pop of pts who received the study tx to which they were randomly assigned.

Methods: Pts with RRMM who received 2–4 prior lines of therapy, were TCE (IMiD agents, PI, and daratumumab), and had disease refractory to the last regimen, were randomized 2:1 to receive ide-cel or a std regimen (DPd, DVd, IRd, Kd or EPd). Efficacy (PFS and ORR) and safety were assessed in the mITT pop who received the study tx to which they were randomly assigned.

Results: Of the 386 pts in the ITT pop, 351 received study tx and constituted the mITT pop (225 pts, ide-cel; 126 pts, std regimens); 35 randomized pts in the ITT pop did not receive ide-cel (n=29) or std regimens (n=6). Of the 29 pts who did not receive ide-cel, 5 did not undergo leukapheresis and 24 underwent leukapheresis but did not receive ide-cel due to physician decision (n=7), eligibility criteria (n=6), death (n=4), adverse events (AEs; n=4), and manufacturing failure (n=3). Six pts did not receive std regimens (consent withdrawal [n=3], physician decision [n=2], and progressive disease [PD; n=1]). In the mITT pop, baseline characteristics were generally balanced between tx arms, and comparable to the ITT pop. Among pts who did not receive ide-cel (n=29), a greater proportion had high-risk features vs the mITT pop (R-ISS stage III [38% vs 9%] and higher tumor burden [52% vs 25%]). In the mITT pop, tx with ide-cel led to longer PFS vs std regimens (mPFS [95% CI], 14.5 [12.2−17.3] vs 4.4 [3.4−5.9] mo; HR 0.43; 95% CI 0.33−0.56). ORR was higher with ide-cel vs std regimens (80% vs 44%), with higher rates of deep response (≥complete response: 44% vs 6%). In the mITT pop, grade 3/4 AEs occurred in 213/225 (95%) and 94/126 (75%) pts in the ide-cel and std regimens arms, respectively; most commonly neutropenia (80% vs 40%), anemia (51% vs 18%) and thrombocytopenia (44% vs 17%). Grade 5 AEs occurred in 12% and 6% of pts, of which 4.9% and 2.4%, respectively, were due to PD.

Conclusions: In the mITT pop, the benefit of ide-cel over std regimens was consistent with the ITT pop; while the mPFS for std regimens remained same in both pop, the mPFS for ide-cel was longer in the mITT pop than in the ITT pop, reflecting ide-cel efficacy in infused pts.