CILTACABTAGENE AUTOLEUCEL VS STANDARD OF CARE IN LENALIDOMIDE-REFRACTORY MULTIPLE MYELOMA: PHASE 3 CARTITUDE-4 SUBGROUP ANALYSIS BY CYTOGENETIC RISK

Abstract

Background: The prognosis for patients (pts) with multiple myeloma (MM) who have high-risk (HR) cytogenetics is poor. In the phase 3 CARTITUDE-4 trial, ciltacabtagene autoleucel (cilta-cel) vs standard of care (SOC) significantly improved progression-free survival (PFS; p < 0.0001) in pts with relapsed and lenalidomide-refractory MM after 1–3 prior lines of therapy. Additionally, the proportion of pts with an overall response (OR) (85% vs 67%), complete response or better (≥CR; 73% vs 22%), and minimal residual disease (MRD) negativity rate (10–5; 61% vs 16%) was higher with cilta-cel vs SOC. Aims: To report the efficacy of cilta-cel vs SOC in pts with HR and standard-risk (SR) cytogenetics, including by type of cytogenetic abnormality from a post hoc subgroup analysis of CARTITUDE-4. Methods: Eligibility criteria for CARTITUDE-4 have been previously described. Pts in the cilta-cel arm underwent apheresis, received bridging therapy (pomalidomide, bortezomib, and dexamethasone [PVd] or daratumumab, pomalidomide, and dexamethasone [DPd]), and then a single cilta-cel infusion (target dose, 0.75 × 106 CAR+ viable T cells/kg) 5–7 days after the start of lymphodepletion. The SOC arm received PVd or DPd until progressive disease. HR cytogenetics was defined as pts with ≥1 of the following cytogenetic abnormalities at baseline determined by fluorescence in situ hybridization: del(17p), t(4;14), t(14;16), or gain/amp(1q). SR cytogenetics was defined as pts without del(17p), t(4;14), t(14;16), or gain/amp(1q) at baseline. Efficacy analyses were assessed in the intent-to-treat population (all randomized pts) and are summarized descriptively. Results: In CARTITUDE-4, 394/419 pts were evaluable for cytogenetics and had non-missing data; of these, 255 pts had HR cytogenetics (cilta-cel, n = 123; SOC, n = 132) and 139 had SR cytogenetics (cilta-cel, n = 69; SOC, n = 70). At the data cutoff (Nov 1, 2022), median follow-up was 15.9 mo (range, 0.1–27.3). In pts with HR cytogenetics, median PFS was not reached (NR; 95% CI, 18.4–not estimable [NE]) with cilta-cel vs 10.3 mo (95% CI, 7.6–12.5) with SOC; 12-mo PFS rates were 76% vs 43%, respectively. Among pts with SR cytogenetics, median PFS was NR (95% CI, NE–NE) with cilta-cel vs 20.6 mo (95% CI, 11.2–NE) with SOC; 12-mo PFS rates were 77% vs 59%, respectively. In pts with HR cytogenetics, a greater proportion had an OR (85% vs 66%), ≥CR (73% vs 20%), and MRD negativity (105; 70% vs 14%) with cilta-cel vs SOC. Similarly, in pts with SR cytogenetics a greater proportion had an OR (86% vs 71%), ≥CR (74% vs 26%), and MRD negativity (105; 49% vs 19%) with cilta-cel vs SOC. [YfA[1] Efficacy in pts with t(14;16) was excluded because the small number of pts in the cilta-cel (n = 3) and SOC (n = 7) arms precludes meaningful analyses. Summary/Conclusions: A single infusion of cilta-cel demonstrated favorable efficacy outcomes vs SOC in lenalidomide-refractory MM pts who had HR and standard-risk disease, with generally consistent results across different cytogenetic abnormalities although sample sizes for some individual types were small. Of note, cilta-cel induced comparable OR, ≥CR, and MRD-negativity rates in pts with HR and standard-risk disease, supporting the role of cilta-cel as a potential new SOC in pts with lenalidomide-refractory MM after 1–3 prior lines of therapy. Acknowledgments: This study was funded by Janssen Research & Development, LLC and Legend Biotech USA Inc.