Leaked data from the phase 3 CARTITUDE-4 trial indicate that ciltacabtagene autoleucel (cilta-cel; Carvykti) significantly reduces the risk of disease progression or death in patients with relapsed/refractory multiple myeloma. The study compared cilta-cel to pomalidomide, bortezomib, and dexamethasone (PVd), or daratumumab, pomalidomide, and dexamethasone (DPd) in patients who had received 1 to 3 prior lines of therapy.
The data, initially slated for presentation at the 2023 EHA Hybrid Congress, revealed a 74% reduction in the risk of disease progression or death with cilta-cel. Median progression-free survival (PFS) was not reached in the cilta-cel arm, compared to 12 months in the control arm. The 12-month PFS rate was 76% with cilta-cel and 49% with the control.
The overall response rate (ORR) was 88% in the cilta-cel group and 67% in the control group. Notably, 73% of patients treated with cilta-cel achieved complete response versus 22% with the control. Minimal residual disease (MRD) negativity was observed in 61% of patients in the cilta-cel arm, compared to 16% in the control arm. Overall survival (OS) data were not mature but indicated a trend favoring cilta-cel, with a hazard ratio of 0.78.
Safety Profile
Regarding safety, the data indicated no new safety signals. Cytokine release syndrome (CRS) occurred in 76% of patients receiving cilta-cel, with the majority of cases being grade 1 or 2. Only 1% of patients experienced a grade 3 CRS event, and no grade 4 or 5 events were reported. Immune effector cell–associated neurotoxicity syndrome occurred in 5% of patients, and all events were grade 1 or 2.
Trial Design and Patient Eligibility
The primary endpoint of the CARTITUDE-4 trial was PFS, with secondary endpoints including complete response (CR) rate, stringent CR (sCR) rate, MRD, OS, ORR, health-related quality of life, and safety. Eligible patients had measurable disease at screening, had received 1 to 3 prior lines of therapy including a proteasome inhibitor (PI) and immunomodulatory drug (IMiD), had documented progressive disease on or within 6 months of their last treatment regimen, and were refractory to lenalidomide.
Current Landscape and Prior Approvals
In February 2022, the FDA approved cilta-cel for relapsed/refractory multiple myeloma after 4 or more prior lines of therapy, based on the phase 1b/2 CARTITUDE-1 trial. That trial demonstrated an ORR of 98% and a sCR rate of 78%.
For context, idecabtagene vicleucel (ide-cel; Abecma) in the phase 3 KarMMa-3 trial, showed a median PFS of 13.3 months versus 4.4 months with standard-of-care. The FDA accepted a supplemental biologics license application for ide-cel on April 17, 2023, seeking approval for patients who have received an IMiD, a PI, and an anti-CD38 monoclonal antibody, based on KarMMA-3 data.
