Efficacy and safety of ciltacabtagene autoleucel ± lenalidomide maintenance in newly diagnosed multiple myeloma with suboptimal response to frontline autologous stem cell transplant: CARTITUDE-2 cohort D.

7505 Background: CARTITUDE-2 is a phase 2 multicohort study evaluating ciltacabtagene autoleucel (cilta-cel) across various clinical settings. Cohort D is evaluating cilta-cel ± lenalidomide (len) maintenance in patients (pts) with newly diagnosed multiple myeloma (NDMM) who achieved less than complete response (CR) after autologous stem cell transplant (ASCT) frontline therapy (tx). We report efficacy and safety for this cohort. Methods: Adults with NDMM per IMWG criteria, best response of <CR and ≥stable disease after 4–8 cycles of initial tx, including induction, high-dose chemotherapy and ASCT ± consolidation, and without exposure to CAR-T or anti-BCMA tx received a single cilta-cel infusion (target dose, 0.75×10 6 CAR+ viable T cells/kg) 5–7 d after the start of lymphodepletion. Per protocol, safety was assessed in the first 5 pts with cilta-cel only; subsequently, 12 pts initiated continuous len maintenance ≥21 d post cilta-cel for ≤2 yrs. Primary endpoint was minimal residual disease negativity (MRD neg) at 10 –5 based on next-generation sequencing or flow. Results: As of Sept 5, 2023 (median follow-up, 22 mo range, 5–39), 17 pts received cilta-cel (with len, n=12; without len, n=5). Median age was 54 yrs; 6% had high-risk cytogenetics; and 100% were International Staging System stage I at baseline. Of 15 MRD-evaluable pts, 12 (80%) achieved MRD neg at 10 –5 ; median time to MRD neg was 1 mo (range, 1–6). Overall response rate was 94% (n=16/17; ≥CR, 94%). Median duration of response was not reached, and median time to first response was 1 mo. Progression-free survival (investigator-assessed) and overall survival rates at 18 mo were 94% each. CAR+ T cells peaked in blood at a median of 12 d post infusion (mean, 2187 cells/µL; SD, 2102 cells/µL) and remained detectable for a median of 43 d (range, 26–209). All pts had grade (gr) 3/4 TEAEs. Hematologic TEAEs included neutropenia (94%), lymphopenia (65%), thrombocytopenia (47%), and leukopenia (41%). Infections occurred in 12 (71%) pts (gr 3/4, 29%). CRS occurred in 14 (82%) pts, and median time to onset was 8 d. All CRS events were gr 1/2 and recovered in a median of 3 d. ICANS occurred in 1 pt (gr 1); median time to onset was 7 d and recovery was 1 d. Other neurotoxicities occurred in 6 pts (gr 1, n=1; gr 2, n=4; gr 3, n=1); median time to onset was 21 d and recovery was 70 d (n=4). No MNTs/parkinsonism occurred. 1 pt had a secondary malignancy of gr 3 MDS with an onset on d 353 that was not treatment related per investigator assessment. Conclusions: In pts with NDMM and <CR after frontline ASCT, a single cilta-cel infusion ± len maintenance demonstrated deep responses that were durable. TEAEs were consistent with the known safety profile of cilta-cel. These data show promising efficacy and safety with cilta-cel ± len maintenance in pts with NDMM who achieved <CR after ASCT frontline tx. Clinical trial information: NCT04133636 .