Clin Cancer Res. 2024 May 7. doi: 10.1158/1078-0432.CCR-24-0378. Online ahead of print.
ABSTRACT
In February 2022, the U.S. Food and Drug Administration approved ciltacabtagene autoleucel, a chimeric antigen receptor (CAR) T cell therapy targeting the B-cell maturation antigen (BCMA), for adult patients with relapsed/refractory multiple myeloma (RRMM) after ≥4 lines of therapy including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. Approval was based on overall response rate (ORR), complete response (CR) rate and duration of response (DOR) in 97 adult patients in a single-arm, open-label, multicenter phase 2 trial (CARTITUDE-1 [NCT03548207]). Patients received a single infusion of ciltacabtagene autoleucel, preceded by lymphodepleting chemotherapy. Of the 97 patients evaluable, ORR was 97.9% (95% CI: 92.7, 99.7) with stringent CR rate of 78.4% (95% CI: 68.8, 86.1). After median follow-up of 18 months, median DOR was 21.8 months (95% CI: 21.8, not estimable [NE]) in responders (PR or better) and NE (95% CI: 21.8 months, NE) in patients who achieved stringent CR. Serious adverse reactions occurred in 55% of 97 patients evaluated for safety. Grade 3 or higher cytokine release syndrome and neurologic toxicities occurred in 5% and 11%, respectively, leading to a Risk Evaluation and Mitigation Strategy. Neurologic toxicities included immune effector cell associated neurologic syndrome (ICANS) typically seen with CAR-T products, Parkinsonism, peripheral neuropathy, cranial nerve palsies and Guillain-Barre Syndrome (GBS). One fatal case of hemophagocytic lymphohistiocytosis/macrophage activation syndrome occurred. Prolonged and recurrent grade 3 or 4 cytopenias occurred; a single patient required hematopoietic stem cell rescue.
PMID:38713595 | DOI:10.1158/1078-0432.CCR-24-0378