OAB-024: Updated results from CARTITUDE-1: Ciltacabtagene autoleucel, a B-cell maturation antigen–directed chimeric antigen receptor T (CAR-T) cell therapy, in relapsed/refractory multiple myeloma (RRMM)

Abstract

<h3>Background</h3> Ciltacabtagene autoleucel (cilta-cel) is a CAR-T cell therapy with two B-cell maturation antigen–targeting single-domain antibodies. The phase 1b/2 CARTITUDE-1 study is evaluating cilta-cel in patients (pts) with RRMM. Here we report updated results from a longer median duration of follow-up of 18 months (mos). <h3>Methods</h3> Eligible pts had MM, received ≥3 prior regimens (or were double refractory to a proteasome inhibitor and immunomodulatory drug), and received anti-CD38 antibody. A single cilta-cel infusion (target dose: 0.75×10⁶ CAR+ viable T cells/kg; range, 0.5–1.0×10⁶) was given 5–7 days (d) after lymphodepletion with 300 mg/m² cyclophosphamide and 30 mg/m² fludarabine daily for 3 d. Primary objectives were to assess cilta-cel safety, confirm the recommended phase 2 dose (phase 1b), and evaluate efficacy (phase 2). Cytokine release syndrome (CRS) was graded by Lee et al (Blood 2014) and neurotoxicity by Common Terminology Criteria for Adverse Events (CTCAE), v5.0 in phase 1b. CRS and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded by American Society for Transplantation and Cellular Therapy (ASTCT) criteria in phase 2. Here, Lee et al and CTCAE v5.0 were mapped to ASTCT for CRS and ICANS, respectively. <h3>Results</h3> As of Feb 11, 2021, 97 pts (median of 6 prior lines) received cilta-cel. Overall response rate was 97.9% (95% CI, 92.7–99.7), with 80.4% achieving stringent complete response (sCR) and 94.8% achieving ≥very good partial response. Median time to first response was 1 mo (range, 0.9–10.7), and median time to ≥CR was 2.6 mos (range, 0.9–15.2). Median duration of response was 21.8 mos (95% CI, 21.8–NE). Of 61 pts evaluable for minimal residual disease (MRD), 91.8% were MRD negative at 10^-5. 18-month progression-free survival (PFS) and overall survival rates (95% CI) were 66% (54.9–75.0) and 80.9% (71.4–87.6), respectively. Median PFS was 22.8 mos (95% CI, 22.8–NE) for all pts, and not reached for pts with sCR. Grade 3/4 hematologic adverse events (AEs) ≥20% included neutropenia (95%), anemia (68%), leukopenia (61%), thrombocytopenia (60%), and lymphopenia (50%). CRS occurred in 95% of pts (4% grade 3/4); median time to onset was 7 d (range, 1–12), and median duration was 4 d (range, 1–14, except 1 pt with 97 d duration). CRS resolved in all but one with grade 5 CRS/haemophagocytic lymphohistiocytosis. CAR-T cell neurotoxicity occurred in 21% of pts (grade ≥3, 10%). 21 deaths occurred during the study after cilta-cel infusion: none within the first 30 d, 2 within 100 d, and 19 after 100 d. Ten deaths were due to disease progression, 6 were treatment-related, and 5 were due to AEs unrelated to treatment. <h3>Conclusions</h3> At a median follow-up of 18 mos, a single infusion of cilta-cel yielded early, deep, and durable responses in heavily pretreated pts with RRMM, with manageable safety. Cilta-cel is being investigated in other MM populations in earlier lines of therapy and in outpatient settings.