De-novo central nervous system demyelination following immune checkpoint inhibitors: a multicenter study and systematic literature review

Introduction This database includes the raw data linked with the paper “ De-novo central nervous system demyelination following immune checkpoint inhibitors: a multicenter study and systematic literature review ” that will be submitted for publication to the Journal of Neurology, Neurosurgery and Neuropsychiatry. In this paper, we report a multicentre retrospective case series and a systematic literature review of cases of de novo demyelinating disorders following treatment with immune-checkpoint inhibitors. Methods Retrospective study including consecutive irDEM patients recruited from 2011 to 2025 in 9 European centres. Additional cases were identified through a systematic literature review. IrDEM patients were compared to consecutive neuromyelitis-optica spectrum disorder (NMOSD; n=22) and myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD; n=42). Severe disability was defined as Modified-Rankin Scale (mRS)>2. Results (in brief) We identified 82 irDEM patients, 16 from the multicenter cohort and 66 from the literature review. Median age was 58 years, and 66% were male. IrDEM manifested after a median of 17 weeks following ICIs initiation, and were classified as: i) optic neuritis (n=15, 9 bilateral); ii) myelitis (n=27, 15 longitudinally extensive); iii) brain syndromes (n=8); iv) multifocal (n=32). Glial antibodies were found in 11/82 patients (AQP4-IgG=5; MOG-IgG=2; GFAP-IgG=4). After ICI discontinuation, patients were treated with first-line (77/82, 11/76 with no improvement) and second-line immunotherapy (23/82). Relapses occurred in 17/68 patients (25%), none after second line immunotherapy or ICI rechallenge (attempted in 7). At follow-up, 17/47 patients (36%) had severe disability and 14/82 died(2/14 for irDEM). Compared to NMOSD and MOGAD, irDEM patients were more frequently older, males, multifocal and with severe disability (p<0.001).