Ciltacabtagene autoleucel in patients with lenalidomide-refractory multiple myeloma: CARTITUDE-2 cohort A expansion subgroup.
Authors: Adam D. Cohen, Peter M. Voorhees, Thomas G. Martin, Alexander M. Lesokhin, Jens Hillengass, Jonathan L. Kaufman, Jordan Mark Schecter, Kevin C. De Braganca, Helen Varsos, Christina Corsale, Pankaj Mistry, Qingxuan Song, Mythili Koneru, Muhammad Akram, Octavio Costa Filho, Hermann Einsele
Journal: Journal of Clinical Oncology (2024)

7535 Background: The phase 2 multicohort CARTITUDE-2 study is evaluating ciltacabtagene autoleucel (cilta-cel) in patients (pts) with MM across multiple settings. Cohort A is examining cilta-cel in earlier lines of treatment (tx; LOT) in pts with lenalidomide (len)-refractory multiple myeloma (MM). Initial results for cohort A (N=20; median follow-up, 30 mo) showed cilta-cel led to minimal residual disease negativity (MRD neg) at 10 –5 in 100% of pts with evaluable samples (n=17). ORR was 95% (19/20), median DOR was not reached (NR), and the 24-mo PFS rate was 75%. We report protocol-specified results for the expansion subgroup. Methods: Pts with len-refractory MM after 1–3 LOT, including a PI and IMiD, and no anti-BCMA tx were enrolled. A single cilta-cel infusion (target dose, 0.75×10 6 [range, 0.5–1.0×10 6 ] CAR+ viable T cells/kg) was given 5–7 d after the start of lymphodepletion. Cohort A initially evaluated cilta-cel manufactured by clinical trial processes and later expanded to evaluate cilta-cel manufactured by commercial processes. Primary endpoint was MRD neg at 10 –5 . Efficacy is reported for pts who received cilta-cel at target dose; demographics, baseline disease characteristics, and safety are reported for all treated pts in the expansion subgroup. Results: As of Sept 5, 2023, median follow-up was 16 mo. Of 24 pts enrolled, 23 received cilta-cel infusion (22 at target dose). Median age was 63 y, 52% were male, and 61% were triple-class exposed. Of 16 MRD-evaluable pts, 100% achieved MRD neg at 10 –5 ; median time to MRD neg was 2 mo (range, 1–12). ORR was 91% (20/22). Median DOR was NR; 79% of responders remained in response at 12 mo. Median (range) time to first and best responses were 1 mo (1–10) and 6 mo (1–19), respectively. 12-mo PFS and OS rates were 77% and 91%, respectively. All pts had TEAEs (grade [gr] 3/4, n=22; gr 5, n=1). Hematologic TEAEs included neutropenia (96%), leukopenia (65%), lymphopenia (65%), anemia (57%), and thrombocytopenia (57%). Infections occurred in 8 (35%) pts (gr 3/4, n=1; gr 5, n=1 due to sepsis). CRS occurred in 23 (100%) pts (gr 1/2, n=23); median time to onset was 8 d and recovery was 4 d. ICANS occurred in 4 (17%) pts (gr 1, n=3; gr 4, n=1); median time to onset was 10 d and recovery was 2 d. No other neurotoxicities or MNTs/parkinsonism occurred. 2 pts had secondary malignancies (SM); 1 pt had separate SM of gr 2 basal cell carcinoma and gr 2 squamous cell carcinoma and 1 pt had MDS diagnosed on d 846 that later transformed to AML. Per investigator assessment, SM were not tx-related. Conclusions: In the expansion subgroup of cohort A, cilta-cel led to deep and durable responses in pts with len-refractory MM as early as after first relapse; safety was consistent with the known mechanism of action of CAR-T tx. Results in the expansion and initial subgroups are comparable. Data for CARTITUDE-2 cohort A underscore observations in CARTITUDE-4 which enrolled a similar pt population. Clinical trial information: NCT04133636 .