S185: CARTITUDE-2 COHORT B: UPDATED CLINICAL DATA AND BIOLOGICAL CORRELATIVE ANALYSES OF CILTACABTAGENE AUTOLEUCEL IN PATIENTS WITH MULTIPLE MYELOMA AND EARLY RELAPSE AFTER INITIAL THERAPY

Abstract

Background: CARTITUDE-2 (NCT04133636) is a phase 2, multicohort study evaluating the efficacy and safety of the chimeric antigen receptor (CAR) T-cell therapy ciltacabtagene autoleucel (cilta-cel) in patients (pts) with multiple myeloma (MM). Cohort B enrolled pts who had early relapse after initial therapy. These pts have functionally high-risk disease, as early relapse following autologous stem cell transplantation (ASCT) is associated with poor prognosis, representing an unmet medical need. Aims: To present updated results from CARTITUDE-2 cohort B. Methods: All pts provided informed consent. Pts had MM, received 1 prior line of therapy (proteasome inhibitor and immunomodulatory drug required), had disease progression per International Myeloma Working Group criteria (either ≤12 months after ASCT or ≤12 months after initiation of anti-myeloma therapy for pts not treated with ASCT), and were naive to CAR-T or other anti-B-cell maturation antigen therapies. After lymphodepletion, a single cilta-cel infusion was administered at a target dose of 0.75×106 CAR+ viable T cells/kg. Efficacy and safety were evaluated. The primary endpoint was minimal residual disease (MRD) negativity at 10-5. Patient management strategies were used to minimize risk of movement and neurocognitive adverse events (MNTs). Pharmacokinetic (PK) analyses, including Cmax and Tmax of CAR+ T-cell transgene levels in blood are being performed. Additional assessments include levels of cytokine release syndrome (CRS)-related cytokines (eg, IL-6) over time, peak levels of cytokines by response and CRS, association of cytokine levels with immune effector cell-associated neurotoxicity syndrome (ICANS), and CAR+ T cell CD4/CD8 ratio by response, CRS, and ICANS. Results: 19 pts (median age: 58.0 years [range: 44-67]; 74% male) received cilta-cel as of January 2022; 79% received prior ASCT. Median follow-up was 13.4 months (range: 5.2-21.7). Overall response rate was 100.0%, with 90% of pts achieving ≥complete response, and 95% achieving ≥very good partial response. Median time to first response was 0.95 months (range: 0.9-9.7) and median time to best response was 5.1 months (range: 0.9-11.8). Among 15 MRD-evaluable pts, 14 (93%) achieved MRD 10-5 negativity. Median duration of response was not reached. The 12-month progression-free survival rate was 90%; 12-month event-free rate was 88.9%. CRS occurred in 16 (84.2%) pts (1 grade 4); median time to onset was 8 days (range: 5-11) and all events resolved. ICANS (grade 1) and MNT (grade 3, previously reported) occurred in 1 pt each. 1 pt died post cilta-cel (progressive disease, day 158). Preliminary PK data showed peak expansion of CAR-T cells on day 13.1 (range: 8.96-209.9); median persistence was 76.9 days (range: 40.99-221.8). Summary/Conclusion: This functionally high-risk pt population with early relapse after initial therapy experienced deep and durable responses with manageable safety following a single cilta-cel infusion. Cilta-cel led to responses in pts with ineffective or insufficient response to ASCT. Follow-up is ongoing and responses continue to deepen. We will present updated and detailed PK, cytokine, and CAR-T subset analyses as well as clinical correlation to provide insight into biological correlates of efficacy and safety in these pts.