Cohort B of CARTITUDE-2 evaluated the safety and efficacy of cilta-cel in high-risk patients who experienced early clinical relapse to determine its use in earlier lines of therapy.
Patients with multiple myeloma (MM) who experience early clinical relapse have a median overall survival of less than 2 years, despite treatment with novel agents. Ciltacabtagene autoleucel (cilta-cel) is a chimeric antigen receptor (CAR) T-cell therapy that was recently FDA approved for the treatment of adults after 4 or more prior lines of therapy. CARTITUDE-2 is a phase 2, multicohort study evaluating the safety and efficacy of cilta-cel in earlier lines of therapy. Cohort B enrolled patients who had early relapse after initial therapy with a proteasome inhibitor (PI) and immunomodulatory drug (IMiD). The initial results from cohort B of CARTITUDE-2 showed early and deep responses in patients with early clinical relapse with a manageable safety profile. At the 2022 American Society of Clinical Oncology conference, Niels W. C. J. van de Donk presented updated results from CARTITUDE-2 cohort B.
Patients in cohort B had progressive MM after early relapse with initial therapy (that included a PI and IMiD), which was defined as either ≤12 months after autologous stem-cell transplantation (ASCT) or ≤12 months after initiation of therapy for patients not treated with ASCT. The primary end point was minimal residual disease (MRD) negativity at 105. Additional assessments included overall response rate (ORR), duration of response (DOR), time to response, 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, with 1 patient being treated as an outpatient. After a median follow-up of 13.4 months, the ORR was 100% (95% confidence interval [CI], 82.4-100). Ninety percent achieved complete response or better (95% CI, 66.9-98.7) and 95% of patients achieved very good partial response or better (95% CI, 74.0-99.9). There were 15 MRD-evaluable patients at 105, 14 of which were MRD negative (95% CI, 68.1-99.8). Additional efficacy results included median DOR, which was not met; 12-month progression-free survival rate of 89.5% (95% CI, 64.1-97.3); and a median time to first and best response of 1.0 and 5.1 months, respectively. Peak expansion of CAR T-cells occurred on day 13 and lasted for an average of 77 days.
Cilta-cel had a manageable and predictable safety profile. CRS occurred in 16 patients, 1 of which was grade 3/4 and all of which were resolved. 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 patients; 1 patient experienced grade 1 ICANS with an onset and duration of 11 and 4 days, respectively, while 1 patient had treatment-emergent signs and symptoms of parkinsonism with an onset of 38 days. Across the program, the incidence of parkinsonism decreased after implementation of a patient-management strategy. The most common hematologic adverse event was neutropenia, occurring in 18 patients across all grades, and 11 patients experienced any-grade anemia and thrombocytopenia.
Treatment with cilta-cel in patients with MM who experienced early clinical relapse showed promising efficacy with an ORR of 100% and a tolerable safety profile. These findings support continued investigation into cilta-cel as treatment in earlier lines of therapy.
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