B07: SAFETY AND EFFICACY OF CILTACABTAGENE AUTOLEUCEL, A CHIMERIC ANTIGEN RECEPTOR T-CELL THERAPY DIRECTED AGAINST B-CELL MATURATION ANTIGEN IN PATIENTS WITH MULTIPLE MYELOMA AND EARLY RELAPSE AFTER INITIAL THERAPY: CARTITUDE-2 RESULTS
Authors: NWCJ van de Donk, M Delforge, M Agha, AD Cohen, YC Cohen, J Hillengass, S Anguille, T Kerre, W Roeloffzen, JM Schecter, KC De Braganca, H Varsos, L Wang, M Vogel, E Zudaire, C Corsale, M Akram, D Geng, T Nesheiwat, L Pacaud, P Sonneveld, S Zweegman
Journal: HemaSphere (2022)

Introduction: CARTITUDE-2 (NCT04133636) is a phase 2, multicohort study evaluating the safety and efficacy of ciltacabtagene autoleucel (cilta-cel), a chimeric antigen receptor T-cell (CAR-T) therapy with two B-cell maturation antigen (BCMA)-targeting single-domain antibodies, in patients with multiple myeloma (MM) in various disease settings. Objective: To present the first results from cohort B of CARTITUDE-2, which enrolled patients following early relapse after initial therapy that included a proteasome inhibitor (PI) and immunomodulatory drugs (IMiDs). Methods: Eligible cohort B patients had MM, received 1 prior line of therapy (PI and IMiD required), had disease progression ≤12 months after autologous stem cell transplantation (ASCT) or frontline therapy, and were naive to CAR-T or anti-BCMA therapies. A single cilta-cel infusion (target dose: 0.75×106 CAR+ viable T cells/kg) was given 5–7 days after initiation of lymphodepletion (300 mg/m2 cyclophosphamide and 30 mg/m2 fludarabine daily for 3 days). The primary objective was minimal residual disease (MRD) negativity at 10-5. Adverse events were graded by Common Terminology Criteria for Adverse Events version 5.0 (cytokine release syndrome [CRS]) and immune effector cell associated neurotoxicity syndrome (ICANS) using American Society for Transplantation and Cellular Therapy (ASTCT) criteria. Results: As of April 15, 2021, 18 patients (median age: 57.0 years [range: 44–67]; 78% men) received cilta-cel. Median follow-up was 4.7 months (range: 0.6–13.5), and median time from diagnosis to enrollment was 1.1 years (range: 0.5–1.9). Two (11.1%) patients had high cytogenetic risk and 5 (27.8%) had bone marrow plasma cells >30%; 14 (77.8%) patients had prior ASCT, and 15 (83.3%) were refractory to their prior therapy. Overall response rate was 88.9% (95% CI: 65.3–98.6) with ≥complete response (CR) achieved by 27.8% (95% CI: 9.7–53.5) and ≥very good partial response (VGPR) achieved by 66.7% (95% CI: 41.0–86.7). Median time to first response was 0.9 months (range: 0.9–2.6), median time to best response was 1.4 months (range: 0.9–11.8), and median time to ≥CR was 1.8 months (range: 0.9–11.6). Of 13 patients with ≥3 months follow-up, 5 (38%) achieved ≥CR. All MRD-evaluable patients (n=9) were MRD negative at 10-5 (Figure). Hematologic treatment emergent adverse events (TEAEs) in ≥20% of patients were neutropenia (88.9%), thrombocytopenia (61.1%), anemia (50.0%), leukopenia (27.8%), and lymphopenia (22.2%). CRS occurred in 15 (83.3%) patients (1 grade 4); median time to onset was 8 days (range: 5–11), and median duration was 4 days (range: 1–7). One patient had ICANS (grade 1). One patient experienced movement and neurocognitive TEAEs (grade 3) on Day 38 post cilta-cel infusion. No deaths were reported post cilta-cel infusion. Conclusions: In patients who experienced early clinical relapse or treatment failure to initial therapy, a single cilta-cel infusion resulted in early and deep responses with a manageable safety profile. Responses continue to deepen, and follow-up is ongoing. These findings support the investigation of cilta-cel in earlier lines of therapy and incorporation into potentially curative frontline regimens.