Ciltacabtagene autoleucel (cilta-cel; Carvykti) has demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) compared to standard-of-care (SOC) regimens for patients with relapsed/refractory multiple myeloma. The findings come from the second interim analysis of the phase 3 CARTITUDE-4 trial (NCT04181827), evaluating cilta-cel in lenalidomide-refractory patients who had received one to three prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug.
The open-label, randomized trial compared a single infusion of cilta-cel to SOC regimens, including pomalidomide plus bortezomib and dexamethasone (PVd) or daratumumab plus pomalidomide and dexamethasone (DPd). Patients in the control arm continued treatment until disease progression and were not permitted to cross over to the cilta-cel arm.
The primary endpoint of the study was progression-free survival (PFS), with key secondary endpoints including OS, overall response rate, and minimal residual disease negativity. The updated results on OS will be presented at an upcoming medical meeting and submitted to global regulatory authorities.
Key Findings from CARTITUDE-4
The CARTITUDE-4 trial enrolled patients with relapsed/refractory multiple myeloma who had received 1 to 3 prior lines of therapy and were refractory to lenalidomide. Prior results from the trial, which supported the FDA's approval of cilta-cel in April 2024 for this patient population, showed a 59% reduction in the risk of disease progression or death compared to SOC regimens (HR, 0.26; 95% CI, 0.18-0.38; P <.001) at a median follow-up of 15.9 months.
At the 2023 ASCO Annual Meeting, data showed that median PFS was not reached in the cilta-cel arm vs 11.8 months in the SOC arm (HR, 0.26; 95% CI, 0.18-0.38; P <.0001). The 12-month PFS rate was 75.9% in the cilta-cel arm vs 48.6% in the SOC arm. The overall response rate (84.6% vs 67.3%), complete response rate (73.1% vs 21.8%), and MRD-negative rate (60.6% vs 15.6%) were also superior in the cilta-cel arm compared to the SOC arm.
Expert Commentary
"[Cilta-cel], a one-time infusion, is now the first cell therapy to significantly improve OS vs SOC for patients with myeloma as early as [the] second line," said Jordan Schecter, MD, vice president and Multiple Myeloma Disease Area Leader at Johnson & Johnson Innovative Medicine. Ying Huang, PhD, chief executive officer of Legend Biotech, added, "We are gratified to have observed an OS benefit with a one-time infusion of [cilta-cel] in the latest analysis of the CARTITUDE-4 study."
Cilta-cel's Role in Multiple Myeloma Treatment
Cilta-cel is a BCMA-directed CAR T-cell therapy approved for the treatment of adult patients with relapsed or refractory multiple myeloma. The FDA originally approved cilta-cel in February 2022 for patients who had received four or more prior lines of therapy. The indication was expanded in April 2024 to include patients who have received at least one prior line of therapy, including an immunomodulatory agent and a proteasome inhibitor, and are refractory to lenalidomide.
The therapy's label includes a boxed warning for cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, Parkinsonism, and Guillain-Barre syndrome, as well as associated complications and secondary malignancies.
