Neuropathy following chimeric antigen receptor T-cell therapy: Incidence and associated risk factors.

Abstract

e23448 Background: Neurotoxicity associated with chimeric antigen receptor T-cell (CAR-T) therapy, particularly immune effector cell–associated neurotoxicity syndrome (ICANS), is well described and affects up to 20-70% of patients. However, data on the development of peripheral and cranial neuropathies post CAR-T are limited. We aimed to evaluate the incidence of neuropathy post CAR-T and identify associated risk factors. Methods: We conducted a retrospective cohort study using the TriNetX database (2014–2025). We included adults (age ≥18y) who received any one of the six CAR-Ts (Tisagenlecleucel, Axicabtagene, Brexucabtagene, Lisocabtagene, Idecabtagene and Ciltacabtagene) and had no pre-existing neuropathy within 1 y prior to receiving CAR-T. Neuropathy occurring within 3 months and 1 y post–CAR-T were identified using ICD codes for peripheral or cranial neuropathies. Diabetic, hereditary, and paraneoplastic neuropathies were excluded. We then compared CAR-T recipients who developed neuropathy to those who did not. Univariate analyses were performed to assess associations with demographics, malignancy type, CAR-T product, prior medications, comorbidities and ICANS. Results: Among 2472 CAR-T recipients without pre-existing neuropathy, 357 (14.4%) developed neuropathy within 1 y, including 175 (7%) cases occurring within 3 months. Of the 357 patients, 286 (80%) developed peripheral neuropathy and 71 (20%) developed cranial neuropathy; facial nerve involvement being the most common cranial neuropathy (n = 52, 73%). Patients who developed neuropathy had a mean age of 62.8 y, were predominantly male (64%), non-Hispanic (79%) and White (79%). In univariate analysis, when compared to CAR-T recipients who did not develop neuropathy, we identified factors significantly associated with neuropathy. These included- primary cancer diagnosis of multiple myeloma (34% vs 25%, P < 0.001 ), and solitary plasmacytoma (6% vs 3%, P = 0.02 ); use of CAR-T Ciltacabtagene (14% vs 8%, P < 0.001 ) ; use of cisplatin(8% vs 5%, P < 0.01 ), oxaliplatin (11% vs 7%, P < 0.01 ), gemcitabine (14% vs 8%, P < 0.001 ), carfilzomib (12% vs 6%, P < 0.001 ), talquetamab (6% vs 3%, P = 0.02 ); comorbidities like alcohol use disorder (6% vs 4%, P = 0.03 ), primary hypertension (65% vs 56%, P < 0.01 ), obesity (32% vs 25%, P < 0.01 ), hyperlipidemia (46% vs 37%, P < 0.01 ), and CKD (25% vs 19%, P < 0.01 ). Development of ICANS (18% vs 13%, P < 0.01 ) was also significantly associated with subsequent neuropathy. Conclusions: Neuropathy occurs in 14.4% of patients within 1 y of CAR-T, with half of the cases within 3 months. Peripheral neuropathy predominates, and facial nerve involvement is the most common cranial neuropathy. Risk is higher among patients with multiple myeloma, those receiving Ciltacabtagene and those who develop ICANS. Early neurologic surveillance may be beneficial, particularly in high-risk patients during early post CAR-T period.