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    Comparative Efficacy of CARVYKTI in CARTITUDE-4 versus Alternative Treatments from Daratumumab Clinical Trials for the Treatment of Patients with Lenalidomide-Refractory Multiple Myeloma

    P-016: Comparative Efficacy of CARVYKTI in CARTITUDE-4 versus Alternative Treatments from Daratumumab Clinical Trials for the Treatment of Patients with Lenalidomide-Refractory Multiple Myeloma

    Wednesday, September 25, 2024
    Introduction: In CARTITUDE-4, a phase 3 open-label randomized controlled trial, CARVYKTI (ciltacabtagene autoleucel; cilta-cel), demonstrated superior progression-free survival (PFS) and response rates over daratumumab, pomalidomide and dexamethasone [DPd], or pomalidomide, bortezomib and dexamethasone [PVd], in patients with relapsed and refractory multiple myeloma (RRMM) who are refractory to lenalidomide and have received 1-3 prior line(s) of therapy (LOTs) including an immunomodulatory agent (IMiD) and a proteasome inhibitor (PI). The objective of this abstract is to evaluate the comparative efficacy of cilta-cel vs. a combined group of alternative treatments from daratumumab clinical trials.

    Methods: Data were available for patients from CARTITUDE-4 who received cilta-cel, and from nine daratumumab trials (CASTOR, CANDOR, APOLLO, ALCYONE, MAIA, GRIFFIN, CASSIOPEIA, POLLUX and EQUULEUS) who received active or subsequent treatments with or without daratumumab (mixed cohort of regimens where the most frequently used were carfilzomib and dexamethasone [Kd], daratumumab with Kd [DKd], pomalidomide and dexamethasone [Pd], and DPd, among others). Patients from the daratumumab clinical trials had either newly diagnosed MM (NDMM) or RRMM at study enrolment. Patients were included in the comparator cohort if they satisfied the key eligibility criteria of CARTITUDE-4 at enrollment or at a subsequent line of therapy. Inverse probability of treatment weighting was used to adjust for imbalances between cohorts on key patient characteristics. Overall response rate (ORR), very good partial response or better rate (≥VGPR), complete response or better rate (≥CR), PFS, real-world PFS (RW-PFS) and time to next treatment (TTNT) were assessed. Sensitivity analyses were conducted using different analytical methods and additional characteristics.

    Results: The cilta-cel cohort consisted of 208 patients in the CARTITUDE-4 trial and the combined comparator cohort included 800 patients from the daratumumab trials. After adjustment, baseline covariates were similar across the cohorts. Cilta-cel demonstrated improved ORR (odds ratio [OR]: 3.51; 95% confidence interval [CI]: 2.21-5.65), ≥VGPR (OR: 7.25; 95% CI: 4.66-11.49), and ≥CR (OR: 16.45; 95% CI: 9.99-28.00) vs. the comparator cohort. Cilta-cel was found to reduce the risk of progression or death by 63% (PFS hazard ratio [HR]: 0.37; 95% CI: 0.26-0.52) and 73% (RW-PFS HR: 0.27; 95% CI: 0.19-0.37), and reduce the risk of progression, death or next treatment by 72% (TTNT HR: 0.28; 95% CI: 0.20-0.39). All results were statistically significant (p< 0.0001) and consistent across sensitivity analyses.

    Conclusions: Cilta-cel showed superior efficacy compared to alternative treatments from the daratumumab clinical trials across all outcomes, highlighting the potential for cilta-cel to be considered a new standard of care option for lenalidomide-refractory RRMM patients, who have received 1-3 prior LOTs, including an IMiD and a PI.