An indirect comparison of clinical trial data indicates that ciltacabtagene autoleucel (cilta-cel; Carvykti) provides superior outcomes compared to standard-of-care (SOC) regimens for patients with relapsed or refractory multiple myeloma that is refractory to lenalidomide. The analysis, presented at the 21st Annual International Myeloma Society Annual Meeting, adds further evidence supporting the FDA approval of cilta-cel in April 2024 for this patient population.
Efficacy Outcomes
The indirect comparison included data from 208 patients in the phase 3 CARTITUDE-4 trial who received cilta-cel, and 800 patients from nine other clinical trials who received daratumumab-based regimens. Results showed that in the cilta-cel arm, the overall response rate (ORR) was 83.70%, with a very good partial response (VGPR) or better rate of 79.80%, and a complete response (CR) or better rate of 72.10%. In contrast, the comparator arm had an unadjusted ORR of 51.90%, a VGPR or better rate of 29.10%, and a CR or better rate of 11.90%. After adjusting for differences between the trial populations, the ORR, VGPR or better rate, and CR or better rate were 59.30%, 35.30%, and 13.60%, respectively.
Survival Benefits
Benefits favoring cilta-cel were also observed in progression-free survival (PFS; HR, 0.37; 95% CI, 0.26-0.52; P < .0001), real-world PFS (HR, 0.27; 95% CI, 0.19-0.37; P < .0001), and time to next treatment (HR, 0.28; 95% CI, 0.20-0.39; P < .0001).
Expert Commentary
According to Michel Delforge, MD, PhD, a professor of medicine in the Department of Hematology at the University of Leuven in Belgium and lead author of the study, this analysis confirms the results from the CARTITUDE-4 trial and demonstrates cilta-cel's superiority over other SOC regimens in the relapsed/refractory setting. Delforge noted that the dataset used in the comparison covers a wide range of SOC regimens used in this setting.
Delforge also acknowledged the limitations inherent in indirect comparisons, stating, "The scientific world is not eagerly waiting for too many indirect comparisons… However, here it's confirmatory—nothing more, nothing less."
CARTITUDE-4 Trial
The CARTITUDE-4 trial compared a single infusion of cilta-cel with SOC regimens, including pomalidomide, bortezomib, and dexamethasone, or daratumumab, pomalidomide, and dexamethasone, in patients who had received at least one prior line of therapy and were lenalidomide refractory. The trial demonstrated a clear superiority of cilta-cel over SOC regimens in terms of efficacy, ORR, CR rate, PFS, and overall survival (OS).
Methodology
The comparator dataset included patients from nine large phase 3 trials, where patients received various daratumumab-based treatment regimens. The analysis included data from 204 patients in the cilta-cel arm of CARTITUDE-4 and data from 800 patients who received 1045 eligible lines of therapy, comprising 175 different treatment regimens. The data were adjusted to match the population of CARTITUDE-4 in terms of inclusion criteria.
