Non-ICANS neurological events with cilta-cel in RRMM: Review of the CARTITUDE trials

A review by Rodríguez-Otero et al. evaluating non-immune effector cell-associated neurotoxicity syndrome (non-ICANS) neurological events in patients with relapsed/refractory multiple myeloma (RRMM) treated with ciltacabtagene autoleucel (cilta-cel) across the CARTITUDE-1 (NCT03548207), CARTITUDE-2 (NCT04133636), and CARTITUDE-4 (NCT04181827) trials was published in Clinical Lymphoma, Myeloma and Leukemia. The review focused on cranial nerve palsy (CNP) and immune effector cell (IEC)-parkinsonism, European Society for Blood and Marrow Transplantation (EBMT) recommendations, and a pooled biomarker analysis (N = 355). 

Key data: CNP occurred in 6.3% (21/332) of patients across the CARTITUDE trials, with a median onset at Day 22 after infusion; 86% had a maximum severity of Grade 2 and 14% had Grade 3. Most patients received corticosteroids (19/21), and 90% had complete resolution of facial nerve palsy. IEC-parkinsonism occurred in 6% of patients in CARTITUDE-1 and 1% each in CARTITUDE-2 and CARTITUDE-4, with a median onset of 56 days; treatment responses were variable. EBMT guidance recommends short course corticosteroids for CNP and dexamethasone (10–20 mg; 2–4 times daily) for IEC-parkinsonism, with cyclophosphamide considered for refractory or worsening disease. In the pooled biomarker analysis, Day 14 absolute lymphocyte count (ALC) and chimeric antigen receptor (CAR)+ T cell counts were higher in patients with IEC-parkinsonism vs controls (17,600 vs 970 cells/µL and 5,520 vs 384 cells/µL; both p < 0.0001) and CNP vs controls (2,180 vs 970 cells/µL; p < 0.0001 and 1,230 vs 384 cells/µL; p < 0.001). ALC correlated with CAR+ T cell counts on Day 14 (R = 0.79; p < 0.0001). 

Key learning: These findings emphasize the importance of patient and caregiver education, early post-infusion ALC monitoring, and prompt neurological assessment after cilta-cel infusion, as CNP often resolves and early recognition and intervention may improve the reversibility of IEC-parkinsonism.