B09 CARTITUDE-2 COHORT B 18-MONTH FOLLOW-UP: CILTACABTAGENE AUTOLEUCEL (CILTA-CEL), A BCMA-DIRECTED CAR-T CELL THERAPY, IN PATIENTS WITH MULTIPLE MYELOMA (MM) AND EARLY RELAPSE AFTER INITIAL THERAPY (2023)

Introduction: Cohort B of the multicohort phase 2 CARTITUDE-2 (NCT04133636) study is evaluating cilta-cel in patients with multiple myeloma (MM) and early relapse (≤12 months after autologous stem cell transplant [ASCT] or ≤12 months after start of initial treatment with anti-myeloma therapy). This patient population has functionally high-risk disease and represents an unmet medical need, as progression within 1 year of starting initial therapy is a poor prognostic factor, with overall survival <2 years in these patients. Here we present updated clinical results and cytokine analyses. Methods: Patients with MM, 1 prior line of therapy (proteasome inhibitor and immunomodulatory drug required), early disease progression (≤12 months after ASCT or ≤12 months after start of anti-myeloma therapy for patients who did not undergo ASCT), and treatment-naive to CAR-T/anti-B-cell maturation antigen (BCMA) therapies were eligible. Bridging therapy was permitted between apheresis and CAR-T cell infusion. A single cilta-cel infusion (target dose 0.75×106 CAR+ viable T cells/kg) was administered post lymphodepletion. Safety and efficacy were evaluated. Primary endpoint was minimal residual disease (MRD) negativity by next generation sequencing at 10-5. Management strategies were used to reduce risk of movement/neurocognitive treatment-emergent adverse events (MNTs)/parkinsonism. Pharmacokinetics, CAR-T cell phenotype, and cytokine profiles are also being evaluated. Results: As of June 1, 2022, 19 patients received cilta-cel (median age 58 years [range 44–67]; 74% male; 16% high-risk cytogenetics, 63.2% standard risk, 21.1% unknown) and 16 remained on study. Median follow-up was 17.8 months (range 5.2–26.3). 79% of patients had prior ASCT. Overall response rate was 100% (100% very good partial response or better; 90% complete response or better) (Figure). Median time to first response was 0.95 months (range 0.9–9.7); median time to best response was 5.1 months (range 0.9–11.8). Of 15 MRD-evaluable patients, 14 (93%) achieved MRD 10-5 negativity during the study. Median duration of response was not reached. 12-month event-free rate was 84%; 12-month progression-free survival (PFS) rate was 90%. Most common treatment-emergent AEs (TEAEs) were hematologic (grade 3/4: neutropenia, 90%; lymphopenia, 42%; thrombocytopenia, 26%; leukopenia, 26%). Cytokine release syndrome (CRS) occurred in 16 (84.2%) patients (grade 4, n=1). Median time from cilta-cel infusion to onset of CRS was 8 days (range 5–11); CRS resolved in all patients. Immune effector cell-associated neurotoxicity syndrome (grade 1) occurred in 1 patient. Movement and neurocognitive TEAEs/parkinsonism (grade 3) occurred in 1 patient (previously reported). 3 patients died post cilta-cel at days 158, 417, and 451 due to progressive disease. Interleukin (IL)-6, interferon gamma, IL-2Rα, and IL-10 levels increased after infusion, peaking at days 7–14 and coincident with the timing of CRS, and returning to baseline levels within 2–3 months after infusion. Conclusions: In this functionally high-risk patient population (all of whom relapsed within a year of receiving standard of care upfront therapy, including ASCT [79%]), 90% remained progression-free at 1 year after cilta-cel treatment. At this longer follow-up of 18 months, results show durability and deepening of response to cilta-cel and maintenance of PFS rate, representing a potentially significant advancement in a population with high unmet need.