Abstract
BACKGROUND: Anti-BCMA (B-cell maturation antigen) chimeric antigen receptor (CAR) T-cell therapy has demonstrated high efficacy in patients with relapsed/refractory multiple myeloma (R/R MM). Acute toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), typically occur within two weeks of infusion and resolve promptly. However, data on long-term neurological safety remain scarce. Emerging evidence suggests the possibility of movement and neurocognitive treatment-emergent toxicities (MNTs), characterised by irreversible parkinsonism, cognitive impairment, and personality changes, typically arising a median of 36 days [range: 14-914] after CRS/ICANS resolution. This study aims to prospectively assess the long-term neurological safety of ide-cel in R/R MM patients, using standardized cognitive and motor evaluations. MATERIAL AND METHODS: We conducted a prospective, systematic neurological evaluation in a cohort of R/R MM patients treated with ide-cel between November 2021 and December 2024 at our center. Only progression-free patients were included. Neurological assessments were performed by a neurologist at baseline (≤2 months before infusion) and at follow-up visits up to 18 months [range 10.5-17.3} post-infusion. Assessments included the Montreal Cognitive Assessment (MoCA) for global cognitive function and the motor subscale of the Unified Parkinson’s Disease Rating Scale (UPDRS) for extrapyramidal symptoms. Pre-treatment brain MRI (<3 months) excluded structural abnormalities. CRS and ICANS were retrospectively recorded. Neurotoxicity triggered further neurological assessment. RESULTS: Among 88 patients treated with ide-cel, 40 were excluded due to early relapse, death, or loss to follow-up. Of the 48 eligible patients, 27 remain in follow-up, and 21 have completed full neurological assessments. At baseline, the median MoCA score was 26/30. The highest UPDRS motor score was 4/56, observed in two patients. ICANS was reported in three patients (two Grade 1 and one Grade 4 requiring ICU care). Cognitive and motor scores remained stable between baseline and follow-up assessments, including in those with initially elevated UPDRS scores. CONCLUSION: In this real-world, prospective cohort of ide-cel-treated R/R MM patients, no long-term cognitive or motor deterioration was observed up to 18 months post-infusion. Despite the limited number of patients evaluable at this time point, these preliminary findings support the long-term neurological safety of ide-cel when patients are systematically assessed using standardized tools such as the MoCA and UPDRS. Updated results will be presented at the EANO meeting.