CARTITUDE-4: Cilta-cel meets expectations in lenalidomide-refractory MM

Cilta-cel was superior to the standard of care in patients with lenalidomide-refractory multiple myeloma (MM), results from the phase 3 CARTITUDE-4 trial showed. According to the authors, cilta-cel has the potential to become the new standard of care for patients with lenalidomide-refractory MM after a first relapse.

Cilta-cel is a dual-binding B-cell maturation antigen (BCMA)-directed CAR T-cell therapy, which has demonstrated a median progression-free survival of approximately 3 years in patients with MM who had received at least 3 prior lines of therapy in the previous CARTITUDE-1 trial (NCT03548207) [1]. Progressing from there, Dr Hermann Einsele (University of Würzburg, Germany) presented the primary results of the current phase 3 CARTITUDE-4 trial (NCT04181827), which tested cilta-cel against standard of care in earlier lines of therapy. The trial randomised 419 participants with lenalidomide-refractory MM who had received 1-3 prior lines of therapy 1:1 to cilta-cel or to the standard of care therapy by physician’s choice (DPd or PVd) [2]. The primary outcome measure was progression-free survival (PFS).

After a median follow-up of 15.9 months, the primary endpoint was met: PFS was significantly improved in participants in the cilta-cel arm compared with standard of care (HR 0.26; 95% CI 0.18–0.38; P<0.0001, see Figure). The corresponding 12-month PFS rates were 76% and 49%. This result was consistent across pre-defined subgroups. Dr Einsele added: “Importantly, the data suggest that participants who had received only 1 prior line of therapy may benefit more from cilta-cel than participants having received 2 or 3 prior lines of therapy”. Overall response rates were 84.6% versus 67.3% and the complete response rate was 73.1% in the cilta-cel versus 21.8% in the standard of care arm, respectively. In an as-treated analysis, the complete response rate was even higher in the as-treated population  (99.4% vs 86.4%).

Looking at safety, 85%–90% of the patients experienced neutropenia. These events were almost exclusively grade 3 or 4 events, but mostly resolved to low-grade events by day 30. The grade 3 or 4 infection rate was similar for the 2 arms, with 26.9% in the experimental arm and 24.5% in the control arm. Cytokine release syndrome was seen in 76.1% of the ‘as-treated with cilta-cel’ population, but only 2 cases were grade 3 or 4 events. Finally, neurotoxicity was reported in 20.5% of the participants, including 5 cases that were of grade 3 or 4.

Figure: Primary endpoint of progression-free survival from the CARTITUDE-4 trial [2]



SOC, Standard of care; HR, hazard ratio; CI, confidence interval; mo, months; mPFS, mean progression-free survival; No., number; NE, not estimable.

1. Berdeja JG, et al. Lancet. 2021;398(10297):314–324
2. Einsele H, et al. Phase 3 results from CARTITUDE-4: Cilta-cel versus standard of care (PVd or DPd) in lenalidomide-refractory multiple myeloma. Plenary abstracts session, EHA 2023 Annual Congress, 8─11 June, Frankfurt, Germany.

 

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Posted on 2 August 202327 March 2024