Ciltacabtagene autoleucel, a B-cell maturation antigen–targeting chimeric antigen receptor (CAR) T-cell therapy, significantly slows or stops progression of multiple myeloma when compared with standard-of-care treatments among patients with lenalidomide-refractory disease. Results from the CARTITUDE-4 trial were presented by Dhakal et al at the 2023 ASCO Annual Meeting (Abstract LBA106).
Trial Details
CARTITUDE-4 enrolled 419 participants from 16 countries, including locations in the United States, Europe, Asia, and Australia. The study participants were around 61 years old, 55% were men, and 75% were White.
Patients had already received one to three lines of treatment, including lenalidomide, which was no longer effective. There were 208 participants in the ciltacabtagene autoleucel arm and 211 participants in the standard-of-care treatment arm, which used either a combination of bortezomib, pomalidomide, and dexamethasone or a combination of daratumumab, pomalidomide, and dexamethasone.
CARTITUDE-4 is one of only two phase III clinical trials investigating CAR T-cell therapy in the early lines of therapy for multiple myeloma; CARTITUDE-4 is the only phase III study to currently explore using CAR T-cell therapy after the first relapse of the disease.
Key Findings
After a median follow-up of 16 months, the researchers found that ciltacabtagene autoleucel reduced the risk of disease progression by 74% compared with the standard-of-care treatments in this patient population. Objective response rates were 84.6% in the group assigned to ciltacabtagene autoleucel compared with 67.3% in the group assigned to standard-of-care treatment. Those receiving ciltacabtagene autoleucel also had better measurable residual disease negativity (60.6%) compared with those assigned to standard of care (15.6%).
“Lenalidomide-based therapies are used extensively as front-line treatments, in both young and elderly patients and including [both] those who are transplant-eligible and transplant-ineligible. This causes an increase in the number of cases where the disease no longer responds to lenalidomide early in the course of the disease,” said lead study author Binod Dhakal, MD, of the Medical College of Wisconsin. “These findings show that ciltacabtagene autoleucel is highly effective in patients with lenalidomide-refractory multiple myeloma as early as after first relapse.”
Most participants (97% receiving ciltacabtagene autoleucel and 94% receiving standard of care) experienced grade 3 or 4 adverse events, including infections (27% vs 25%) and low blood cell counts (94% vs 86%), including neutropenia, thrombocytopenia, and anemia. Seventy-six percent of participants who received ciltacabtagene autoleucel developed cytokine-release syndrome, and around 5% of those receiving the CAR T-cell therapy developed immune effector cell–associated neurotoxicity syndrome.
Next Steps
The researchers will continue to follow the study participants to determine the long-term effects of ciltacabtagene autoleucel. Additional analyses of the data are ongoing, such as health-related quality of life, subgroup analyses, and biomarker analyses. Ciltacabtagene autoleucel is also being studied as front-line therapy in additional ongoing clinical trials.
ASCO Perspective
“Lenalidomide has become a foundation of care for people with [multiple] myeloma, but as its use has expanded, so has the number of patients whose disease will no longer respond to the treatment. Ciltacabtagene autoleucel has not only shown that it delivers remarkably effective outcomes compared to patients’ current options, but also that it can be used safely earlier in the treatment phase,” said ASCO Expert Oreofe Odejide, MD.
Disclosure: The was funded by Janssen Research & Development and Legend Biotech USA. For full disclosures of the study authors, visit coi.asco.org.
