An indirect comparison indicates that ciltacabtagene autoleucel (cilta-cel; Carvykti) may offer superior outcomes compared to standard-of-care (SOC) regimens for patients with lenalidomide-refractory relapsed/refractory multiple myeloma. The analysis, which was presented at the 21st Annual International Myeloma Society Annual Meeting, combined data from the phase 3 CARTITUDE-4 trial (NCT04181827) and nine other clinical trials, suggesting a significant advantage for cilta-cel in this patient population.
The CARTITUDE-4 trial findings supported the FDA's April 2024 approval of cilta-cel for adult patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent, and who are refractory to lenalidomide.
Response Rates
The indirect comparison assessed 208 patients who received cilta-cel in the CARTITUDE-4 trial and 800 patients who received daratumumab (Darzalex)-based regimens across nine other clinical trials. The cilta-cel arm demonstrated an overall response rate (ORR) of 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 showed 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 for the comparator arm were 59.30%, 35.30%, and 13.60%, respectively.
Progression-Free Survival
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
In an interview, Michel Delforge, MD, PhD, a professor of medicine at the University of Leuven in Belgium and lead study author, highlighted the importance of these findings. "This study confirms the results from CARTITUDE-4 and shows that cilta-cel, based on this indirect comparison, has a clear superiority over all the other SOC regimens that are used in the relapsed/refractory setting," Delforge stated. He also noted the limitations inherent in indirect comparisons but emphasized that the results are confirmatory, reinforcing the benefits observed in the CARTITUDE-4 trial.
Delforge further elaborated on the rationale for the study, explaining that while CARTITUDE-4 demonstrated the superiority of cilta-cel over two specific SOC regimens, it was crucial to compare cilta-cel with a broader range of treatments commonly used in clinical practice. The analysis included data from nine large phase 3 trials featuring daratumumab-based regimens, encompassing 175 different treatment regimens.
Clinical Significance
The clinical significance of these results lies in the confirmation of cilta-cel's efficacy and its potential to improve outcomes for patients with relapsed/refractory multiple myeloma. The data suggest that cilta-cel offers a substantial advantage over various SOC regimens, providing a valuable treatment option for this challenging patient population. However, the authors acknowledge the limitations of indirect comparisons and emphasize the need for cautious interpretation of the results.
