Despite novel treatment options, patients with multiple myeloma (MM) who experience early clinical relapse have a median overall survival of <2 years, highlighting the need for more durable treatment options for these patients.
Ciltacabtagene autoleucel (cilta-cel) is a CAR T-cell therapy; its safety and efficacy are currently being investigated in patients with relapsed/refractory MM in CARTITUDE-2, a phase 2, multicohort study. van de Donk and colleagues recently released an analysis of data from cohort B in this study, which included patients who had early relapse after initial therapy with a proteasome inhibitor (PI) and immunomodulatory drug (IMiD). The first results from cohort B of CARTITUDE-2 showed early and deep responses in patients with early clinical relapse to initial therapy, with a manageable safety profile.
Patients in cohort B had progressive MM after early relapse following initial therapy with a PI and IMiD. Early relapse was defined as disease progression ≤12 months after autologous stem-cell transplantation (ASCT) or ≤12 months of initiation of therapy for patients not treated with ASCT. The primary end point was minimal residual disease (MRD) negativity at 10-5. Additional assessments included overall response rate (ORR), complete response (CR), very good partial response (VGPR), progression-free survival (PFS), time to response, duration of response (DOR), and incidence and severity of adverse events, including cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS).
As of January 2022, 19 patients had received cilta-cel; 1 patient was treated in the outpatient setting. After a median follow-up of 13.4 months, ORR was 100%, CR was 90%, and VGPR was 95%. A total of 15 MRD-evaluable patients were at 10-5, and 14 (93.3%) of these achieved MRD negativity. In addition, 12-month PFS rate was 89.5%, median time to first response was 1.0 month, and median time to best response was 5.1 months. Median DOR was not met. Peak expansion of CAR T-cells occurred on day 13 and lasted for a median of 77 days.
The safety of cilta-cel was manageable and predictable. CRS occurred in 16 (84%) patients, 1 of whom was grade 3/4, and was resolved in all patients. Median time to onset of CRS was 8 days, with an average duration of 3.5 days. Higher cytokine levels were associated with CRS severity. Neurotoxicity occurred in 5 (26%) patients; 1 patient experienced grade 1 ICANS with onset at 11 days and duration of 4 days; 1 patient had treatment-emergent signs and symptoms of parkinsonism with an onset at 38 days. Across the CARTITUDE program, the incidence of parkinsonism decreased after implementation of a patient management strategy. The most common hematologic adverse event was neutropenia, occurring in 18 (95%) patients across all grades, and 11 (58%) patients experienced any grade anemia or thrombocytopenia.
Treatment with cilta-cel in patients with MM who experienced early clinical relapse showed promising efficacy with a tolerable safety profile. These findings support continued investigation into cilta-cel as treatment to be used in earlier lines of therapy.
Source
van de Donk NWCJ, Cohen A, Cohen Y, et al. Biological correlative analyses and updated clinical data of ciltacabtagene autoleucel (cilta-cel), a BCMA-directed CAR-T cell therapy, in patients with multiple myeloma (MM) and early relapse after initial therapy: CARTITUDE-2, cohort B. Presented at: American Society of Clinical Oncology Annual Meeting; June 3-7, 2022; Chicago, IL.