Ciltacabtagene autoleucel (cilta-cel) vs standard of care (SOC) in patients (pts) with relapsed/refractory multiple myeloma (MM): CARTITUDE-4 survival subgroup analyses.

Abstract

7539 Background: In CARTITUDE-4, a single cilta-cel infusion significantly improved progression-free survival (PFS; hazard ratio [HR] weighted, 0.29 [95% CI, 0.22–0.39]) and overall survival (OS; HR, 0.55 [0.39–0.79]; P =0.0009) vs SOC in pts with relapsed and lenalidomide-refractory MM after 1–3 prior lines of treatment (pLOT) at 33.6 mo median follow-up (Mateos et al, IMS 2024). PFS and OS from subgroups in the intent-to-treat (ITT) population are reported. Methods: Pts randomized to cilta-cel underwent apheresis, received pomalidomide, bortezomib, and dexamethasone (PVd), or daratumumab, pomalidomide, and dexamethasone (DPd) bridging treatment, lymphodepletion, and then cilta-cel infusion. Pts randomized to SOC received physician’s choice of PVd or DPd until progression. HR for PFS was analyzed using unweighted Cox proportional hazards model for the ITT set. Results: As of May 1, 2024, median follow-up was 33.6 mo. PFS and OS benefit of cilta-cel over SOC in the ITT analysis was consistent across pts with standard-risk cytogenetics and high-risk cytogenetics, defined as del(17p), t(4;14), t(14;16), or gain/amp(1q) (Table). Comparing cilta-cel (n=21) vs SOC (n=18) in pts with extramedullary disease (EMD), median PFS was 13 mo vs 4 mo (HR, 0.71 [95% CI, 0.34–1.49]), respectively, and median OS was not reached (NR) vs 16 mo (HR, 0.61 [95% CI, 0.26–1.47]). In pts with 1, 2, or 3 pLOT (cilta-cel, n=68, 83, 57; SOC, n=68, 87, 56), median PFS was NR with cilta-cel across all pLOT vs 17 mo (HR, 0.41 [95% CI, 0.25–0.67]), 12 mo (HR, 0.30 [95% CI, 0.19–0.49]), and 8 mo (HR, 0.20 [95% CI, 0.11–0.34]) with SOC, respectively; median OS was NR with cilta-cel across all pLOT vs NR (HR, 0.56 [95% CI, 0.28–1.11]), NR (HR, 0.63 [95% CI, 0.36–1.09]), and 34 mo (HR, 0.49 [95% CI, 0.26–0.91]) with SOC. Conclusions: ITT analysis showed that cilta-cel improved PFS and OS vs SOC in all subgroups, including pts with EMD and 1 pLOT and beyond. Compared with SOC, cilta-cel improved PFS and OS in pts with high-risk cytogenetics, suggesting it may overcome the poor prognosis associated with these high-risk features. These data continue to support a positive benefit-risk ratio for cilta-cel in pts with lenalidomide-refractory MM as early as after first relapse. Clinical trial information: NCT04181827 . Cilta-cel, n SOC, n Median PFS cilta-cel, mo Median PFS SOC, mo HR (95% CI) Median OS cilta-cel, mo Median OS SOC, mo HR (95% CI) Standard-risk cytogenetics 69 70 NR 21 0.43 (0.26–0.72) NR NR 0.62 (0.33–1.19) High-risk cytogenetics a 123 132 37 10 0.38(0.27–0.52) NR 38 0.54(0.35–0.85) del(17p) 49 43 30 9 0.40 (0.24–0.68) NR NR 0.52 (0.26–1.04) t(4;14) 30 30 37 7 0.34 (0.17–0.68) NR 27 0.46 (0.20–1.08) gain/amp(1q) 89 107 37 10 0.39 (0.27–0.57) NR 38 0.58 (0.35–0.96) ≥2 cytogenetic abnormalities a 43 49 30 7 0.43 (0.25–0.73) NR 23 0.57 (0.30–1.07) a Cytogenetic abnormalities: del(17p), t(4:14), t(14;16), or gain/amp(1q).