As reported in The Lancet Oncology by Einsele et al, an updated analysis of the phase III CARTITUDE-4 trial has shown that a single infusion of ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen–directed chimeric antigen receptor (CAR) T-cell therapy, prolonged overall survival vs standard of care in patients with lenalidomide-refractory multiple myeloma. The previously reported primary analysis showed prolonged progression-free survival with cilta-cel.
Study Details
In the U.S. multicenter open-label trial, 419 patients with one to three previous treatment lines, including a proteasome inhibitor and an immunomodulatory drug, were randomly assigned between July 2020 and November 2021 to receive a single infusion of cilta-cel at 0.75 × 106 CAR T cells/kg (n = 208) or standard of care (n = 211; consisting of pomalidomide/bortezomib/dexamethasone or daratumumab/pomalidomide/dexamethasone). The current report features updated findings in progression-free survival and results of a prespecified second interim analysis of overall survival in the intention-to-treat population.
Key Findings
At a median follow-up of 33.6 months (interquartile range = 20.3–35.0 months), median progression-free survival was not reached (95% confidence interval [CI] = 34.5 months to not evaluable) in the cilta-cel group vs 11.8 months (95% CI = 9.7–14.0 months) in the standard-of-care group (hazard ratio [HR] = 0.29, 95% CI = 0.22–0.39).
In the second interim analysis, median overall survival was not reached (95% CI = not evaluable to not evaluable) in the cilta-cel group vs not reached (95% CI = 37.7 months to not evaluable) in the standard-of-care group (HR = 0.55, 95% CI = 0.39–0.79, P = .0009).
As assessed by the Multiple Myeloma Symptom and Impact Questionnaire, worsening of symptoms occurred in 30 patients in the cilta-cel group and 49 in the standard of care group. Median time to symptom worsening was not reached (95% CI = not evaluable to not evaluable) in the cilta-cel group vs 34.3 months (95% CI = 32.2 months to not evaluable) in the standard of care group (HR = 0.38, 95% CI = 0.24–0.61).
Rates of maximum grade 3 adverse events were 14% in the cilta-cel group vs 37% in the standard of care group, and rates of maximum grade 4 events were 75% vs 56%; most of these events were cytopenias. Second primary malignancies occurred in 13% vs 12% of patients. Treatment-related death occurred in six patients in the cilta-cel group (four due to infection) and in five patients in the standard of care group (all due to infection).
The investigators concluded: “The significantly improved overall survival and patient-reported measures in CARTITUDE-4 reinforce the use of cilta-cel in treating relapsed or refractory multiple myeloma as early as after first relapse.”
Hermann Einsele, MD, of Universitatsklinikum Wurzburg, Medizinische Klinik und Poliklinik II, Wurzburg, Germany, is the corresponding author for The Lancet Oncology article.
DISCLOSURE: The study was funded by Johnson & Johnson and Legend Biotech USA. For full disclosures of the study authors, visit thelancet.com.
