OBJECTIVES: Compare baseline characteristics and clinical outcomes of patients in the CARTITUDE-1 study receiving ciltacabtagene autoleucel (cilta-cel) considered out-of-specification (OOS) per FDA commercial release criteria versus in-specification cilta-cel.

METHODS: Cilta-cel is a chimeric antigen receptor T-cell therapy approved for treatment of relapsed/refractory multiple myeloma after ≥4 prior lines of therapy, including a proteasome inhibitor, immunomodulatory drug, and anti-CD38 monoclonal antibody, which demonstrated early, deep, and durable responses in CARTITUDE-1. Patients who met inclusion criteria and enrolled in CARTITUDE-1 were identified post hoc as having received OOS cilta-cel. OOS was defined as receiving cilta-cel that did not meet or had insufficient data to confirm ≥1 predefined commercial product release criteria.

RESULTS: Of the 97 cilta-cel–treated patients in CARTITUDE-1, we identified 16 who received OOS cilta-cel. Baseline characteristics were generally comparable with the other 81 patients (non-OOS); notable differences included higher median age (66 years vs 60 years), lower incidence of plasmacytomas (6.3% vs 22.2%), and higher incidence of high-risk cytogenetics (37.5% vs 21.0%) in OOS versus non-OOS groups, respectively. At 27.7-month median follow-up, overall response rates were 93.8% and 98.8%, with stringent complete response rates of 81.3% and 82.7% for OOS and non-OOS patients, respectively. Median duration of response was not estimable (NE) for the 15 OOS responders (95% CI 9.4–NE) and 80 non-OOS responders (95% CI 24.3–NE). Medians for progression-free survival and overall survival were NE for both groups. There were no significant differences in rates of cytokine release syndrome (100% vs 93.8%) or neurotoxicity (31.3% vs 19.8%), including immune effector cell-associated neurotoxicity syndrome (12.5% vs 17.3%), in OOS versus non-OOS groups, as expected.

CONCLUSIONS: This limited post hoc analysis showed no significant differences in efficacy or safety between OOS and non-OOS cilta-cel based on commercial specifications applied to CARTITUDE-1, but additional real-world studies will be needed.