MM-181 CARTITUDE-1: Two-Year Post Last Patient in (LPI) Results From the Phase 1b/2 Study of Ciltacabtagene Autoleucel (Cilta-Cel), a B-Cell Maturation Antigen (BCMA)-Directed Chimeric Antigen Receptor T (CAR-T) Cell Therapy, in Patients With Relapsed/Refractory Multiple Myeloma (RRMM)

Context: Cilta-cel, a CAR-T cell therapy with 2 BCMA–targeting single-domain antibodies, led to early, deep, and durable responses in heavily pretreated patients with RRMM in the phase 1b/2 CARTITUDE-1 study (NCT03548207). Objective: To report updated results from CARTITUDE-1. Data 2-years post LPI (~30-month median follow-up [MFU]) will be presented; here we report results at 21.7-month MFU. Patients: Eligible patients with RRMM had ≥3 prior lines of therapy (LOT) or were refractory to a proteasome inhibitor (PI) and immunomodulatory drug (IMiD) and had received a PI, IMiD, and anti-CD38 antibody. Intervention: After apheresis, bridging therapy was allowed. A single infusion of cilta-cel (target dose 0.75×10⁶ CAR+ viable T cells/kg) was administered 5–7 days after lymphodepletion. Main Outcome Measures: Cilta-cel safety and efficacy were the primary objectives. Assessments included response (per IMWG criteria by independent review committee) and minimal residual disease (MRD) negativity (at 10^-5 by next-generation sequencing). Results: As of July 22, 2021, 97 patients (59% male; median age 61 years; median 6 [range 3–18] prior LOT) received cilta-cel. Overall response rate was 97.9% (94.9% very good partial response; 82.5% stringent complete response). Median times to first response, best response, and ≥complete response were 1.0, 2.6, and 2.9 months, respectively. Median duration of response was not reached. Among 61 MRD-evaluable patients, 92% were MRD negative (10^-5), sustained for ≥6 months in 44% and ≥12 months in 18%. Progression-free survival (PFS) at 2 years was 60.5%. Median PFS and overall survival were not reached. PFS rates at 2 years in patients with MRD negativity sustained for ≥6 months and ≥12 months were 91% and 100%, respectively. No new safety signals, new events of CAR-T cell neurotoxicity, movement and neurocognitive treatment-emergent adverse events, or treatment-related deaths have occurred since 1-year MFU. Over ~2 years MFU, 15 second, primary malignancies were reported in 11 patients. Conclusions: At ~2 years MFU, a single infusion of cilta-cel resulted in deepening and durable responses and manageable safety in heavily pretreated patients with RRMM. Additional research is ongoing to evaluate cilta-cel in earlier LOT and outpatient settings across the CARTITUDE program (NCT04133636, NCT04181827, NCT04923893).