Neurologic Outcomes in People with Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder Exposed To Immune Checkpoint Inhibitors

ObjectiveTo determine neurologic outcomes in people living with multiple sclerosis (pwMS) and neuromyelitis optica spectrum disorder (NMOSD) after exposure to immune checkpoint inhibitors (ICIs). BackgroundICIs are associated with immune-related adverse events (irAEs) including CNS demyelination and exacerbation of pre-existing autoimmune diseases. The incidence of ICI-induced disease activity in pwMS and NMOSD (pwMS+) is unknown. Design/MethodsPwMS+ who were treated with ICIs were identified by retrospective chart review at 8 tertiary medical systems. Participating sites were recruited through the Medical Partnership 4 MS+ network. Using a structured instrument, data on MS+ history, cancer history, treatments, and outcomes were collected. ResultsWe identified 65 individuals (72% female) with MS and 4 with NMOSD who were treated with ICIs (median age 66yo). The median time from last relapse in pwMS prior to ICI initiation was 9 years. During a median of 6-months of ICI therapy, only 2 pwMS (3.4%) were diagnosed with a relapse during during ICI treatment, one patient with asymptomatic demyelinating lesions and the other with new brain lesions with mild worsening in gait that resolved with oral steroids. Two of the four NMOSD patients had new disease activity on ICI, one while being concomitantly treated with inebulizumab. In this patient, within 24 hours of the first dose of pembrolizumab, they developed an enhancing longitudinal extensive cervical cord lesion resulting in significant persistent disability. Three patients (4.5%) had non-MS+ nervous system irAEs and 21 (32.3%) had non-neurologic irAEs. Twenty-five (38.5%) subjects had either partial or complete remission of their cancer. ConclusionsIn this cohort study of pwMS+, who were predominantly older and not on DMT, MS relapses following ICI treatment were rare and mild. In contrast, our preliminary NMOSD cohort suggests that ICIs may be able to trigger severe NMOSD disease activity even in the setting of B-cell depleting therapy.