Cilta-cel versus conventional treatment in patients with relapse/refractory multiple myeloma.

Abstract

8030 Background: CARTITUDE-1 is a single arm study of Ciltacabtagene autoleucel (cilta-cel; JNJ-68284528) anti-BCMA CAR-T cell therapy in US patients (pts) with relapsed multiple myeloma (RRMM) refractory to both IMiD and proteasome inhibitor (PI) or with at least 3 prior lines of therapy and previously exposed to anti-CD38 monoclonal antibody (MoAb). While recently reported efficacy results of cilta-cel were encouraging, it is unknown how they compare with similar pts receiving conventional (non CAR-T) treatment. Methods: We utilized a contemporary US-based dataset of pts with MM refractory to anti-CD38 MoAb (MAMMOTH) to identify pts who would meet eligibility for CARTITUDE-1 and who received conventional therapy. We analyzed the intent-to-treat population (ITT) in CARTITUDE-1, defined as pts who underwent apheresis (N=113) and a modified ITT population (mITT) defined as subset of pts who received cilta-cel at the RP2D (N=97). From the MAMMOTH dataset, we identified a population corresponding to CARTITUDE-1 ITT (N=190) and a mITT population, pts without death or progression within 47 days (median time between apheresis and cilta-cel infusion) from onset of therapy (N=122). We calculated propensity scores (PS) with demographics, N of prior therapies, cytogenetics and refractoriness to MM agents as covariates. An analyst blinded to outcomes performed nearest neighbor 1:1 PS matching. We analyzed overall response rate (ORR), progression-free (PFS) and overall survival (OS) for ITT and mITT in CARTITUDE-1 vs matching MAMMOTH cohorts. Results: Ninety-five ITT (75 received bridging therapy, 82 received cilta-cel) and 69 mITT (54 received bridging) CARTITUDE-1 pts matched MAMMOTH pts (Table). Among the pts in the MAMMOTH ITT cohort 34% received pomalidomide, 24% anti-CD38 MoAb, 19% carfilzomib and 35% cytotoxic chemotherapy in next therapy. ORR in the ITT cohorts was higher in CARTITUDE-1 (84% vs. 28%). Compared to their MAMMOTH counterparts, pts in CARTITUDE-1 ITT cohort had improved PFS (12 mo. 73% vs. 12%) and OS (12 mo. 83% vs 39%). Between the mITT cohorts, CARTITUDE-1 pts had superior ORR (96% vs. 30%), PFS (12 mo 79% vs. 15%) and OS (12 mo. 88% vs. 41%). Conclusions: In pts with RRMM beyond therapy with IMID, PI, and anti-CD38 MoAb, treatment with cilta-cel is associated with higher response rate and superior PFS and OS when compared to conventional treatment.[Table: see text]