Phase III CARTITUDE-4 Trial Meets Primary Endpoint in Lenalidomide-Refractory Multiple Myeloma

Ciltacabtagene autoleucel showed a “favorable” risk-benefit profile across populations of patients with lenalidomide-refractory multiple myeloma (MM), according to results from the phase III CARTITUDE-4 trial.

Binod Dhakal, MD, of the Medical College of Wisconsin, and colleagues presented the data during the 2023 American Society of Clinical Oncology Annual Meeting.

The global randomized controlled trial compared ciltacabtagene autoleucel with standard of care in patients with MM who were refractory to lenalidomide. Eligible patients had received one to three prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug.

The patients were randomized to receive ciltacabtagene autoleucel (n=208) or standard of care (n=211). The standard of care was the physician’s choice of pomalidomide, bortezomib, and dexamethasone (n=28) or daratumumab, pomalidomide, and dexamethasone (n=183), which patients received until progression.

A total of 176 patients received ciltacabtagene autoleucel as study treatment, 20 more received it after disease progression on bridging therapy, and 208 patients received the standard of care. The researchers balanced baseline characteristics between the randomized treatment groups.

Patients who were randomized to the chimeric antigen receptor (CAR) T-cell therapy received physician’s choice of bridging therapy followed by a single infusion of ciltacabtagene autoleucel five to seven days after lymphodepletion. No manufacturing failures were reported. The median dose was 0.71×10⁶ CAR-T cells/kg.

The primary endpoint was progression-free survival (PFS) in the intent-to-treat population. The median follow-up was 16 months at the data cutoff of November 1, 2022.

The study met its primary endpoint, as ciltacabtagene autoleucel reduced the risk of progression or death by 74% (hazard ratio [HR], 0.26; P<.0001). The median PFS was not estimable in the patients receiving ciltacabtagene autoleucel, while it was 12 months in those receiving standard of care. Patients who received the CAR-T therapy had a 12-month PFS rate of 76%, while it was 49% in patients receiving standard of care.

The overall response rate was 85% in patients who received ciltacabtagene autoleucel, while it was significantly lower at 67% in patients receiving standard of care (P<.0001).

The proportion of patients achieving at least a complete response was 73% in the group receiving ciltacabtagene autoleucel, while it was significantly lower at 46% in patients receiving standard of care (P<.0001). There were also significant differences in the percentage of patients achieving measurable residual disease (MRD) negativity, with a rate of 61% in those receiving the CAR-T therapy, and a rate of 16% in those receiving standard of care.

Grade 3 or 4 adverse events (AEs) occurred in 97% of patients receiving the CAR T therapy and in 94% of those receiving standard of care. Grade 3 to 4 infections occurred in 27% of patients receiving ciltacabtagene autoleucel, and in 25% of those receiving standard of care. Grade 3 to 4 cytopenias occurred in 94% of patients receiving the CAR-T and in 86% of those receiving standard of care.

Among the group receiving ciltacabtagene autoleucel, 39 patients died, including 14 due to progressive disease. Among those receiving standard of care, 46 patients died, including 30 due to progressive disease. In the patients who received CAR-T as study treatment (n=176), 76% had cytokine release syndrome, while 5% had immune effector cell-associated neurotoxicity syndrome.

A single ciltacabtagene autoleucel infusion “significantly improved PFS” versus standard of care in patients with lenalidomide-refractory MM who had received one to three prior lines of therapy, with a
“favorable benefit/risk profile” across patient populations,  according to Dr. Dhakal and colleagues.

“The 74% reduction in progression or death and high rates of CR and MRD negativity highlight the potential for [ciltacabtagene autoleucel] to become a key therapy for [patients] with MM after first relapse,” the study’s authors concluded.

Reference

Dhakal B, Yong K, Harrison SJ, et al. First phase 3 results from CARTITUDE-4: Cilta-cel versus standard of care (PVd or DPd) in lenalidomide-refractory multiple myeloma. Abstract LBA106. Presented at the 2023 American Society of Clinical Oncology Annual Meeting; June 2-6, 2023; Chicago, Illinois.