OA-47: Additional analysis of CARTITUDE-4: Cilta-cel vs standard of care (PVd or DPd) in lenalidomide-refractory patients with multiple myeloma and 1-3 prior lines of therapy

Introduction: CARTITUDE-4 is a global, open-label, randomized controlled trial (NCT04181827) comparing the chimeric antigen receptor (CAR)-T cell therapy ciltacabtagene autoleucel (cilta-cel) with physician’s choice of standard of care (SOC; pomalidomide, bortezomib, and dexamethasone [PVd] or daratumumab, pomalidomide, and dexamethasone [DPd]) in lenalidomide (len)-refractory patients (pts) with multiple myeloma (MM). Cilta-cel significantly improved progression-free survival (PFS) vs SOC (median not reached [95% CI 22.8–not estimable] vs 11.8 months [mo] [95% CI, 9.7–13.8], hazard ratio (HR) 0.26 [95% CI, 0.18–0.38]; P< 0.0001) in the intent-to-treat (ITT) population. Here we report outcomes from prespecified subgroup analyses in the ITT population.

Methods: Eligible pts were len-refractory with 1–3 prior lines of therapy (LOT), including a proteasome inhibitor and immunomodulatory drug, and ECOG performance status score of ≤1. Pts randomized to cilta-cel underwent apheresis, received physician’s choice of PVd or DPd bridging treatment (tx), and then 1 cilta-cel infusion (target dose, 0.75×10⁶ CAR+ viable T cells/kg) 5–7 days after start of lymphodepletion. Pts randomized to SOC received physician’s choice of PVd or DPd until progression. Primary endpoint was PFS, analyzed using a weighted method to focus on PFS after the period during which both arms were on the same tx. Subgroup analyses of PFS was reported with HRs and 95% CIs.

Results: Pts were randomized between July 2020 and November 2021. As of November 1, 2022, median follow-up was 15.9 mo (range, 0.1–27). 208 pts were randomized to cilta-cel (of whom 176 received cilta-cel) and 211 to SOC. Arms were balanced at baseline; 32.5% of pts had 1 prior LOT and 6.2% were ISS stage III. 61.2% of pts had high-risk cytogenetics (ie, del(17p), t(14;16), t(4;14) or gain/amp(1q)); 22.0% had ≥2 high-risk abnormalities. 18.9% had soft tissue plasmacytomas, 20.5% had bone marrow plasma cells ≥60%, and 15.0% of pts had triple-class refractory disease. 12.9% of pts received PVd; 87.1% received DPd. Cilta-cel significantly improved PFS vs SOC in all subgroups analyzed, including pts aged < 65 yrs, HR 0.24 (95% CI, 0.15–0.38), and 65–75 yrs, 0.34 (0.19–0.61); with 1 prior LOT, 0.35 (0.19–0.66); ISS stage III, 0.33 (0.11–0.95); ≥1 cytogenetic high-risk abnormality, 0.25 (0.16–0.38); ≥2 high-risk abnormalities, 0.33 (0.17–0.64); soft tissue plasmacytomas, 0.39 (0.21–0.75); bone marrow plasma cells ≥60%, 0.28 (0.14–0.59); triple-class refractory disease, 0.15 (0.05–0.39), as well as pts treated with PVd, 0.31 (0.13–0.72) and DPd, 0.26 (0.18–0.39).

Conclusions: Cilta-cel significantly improved PFS across all analyzed subgroups of the ITT population, including by age, in those with high-risk features, after first relapse, and vs both SOC regimens. Benefit shown was similar to that seen in the overall ITT population, confirming efficacy of a single cilta-cel infusion in a range of clinically relevant MM subgroups.