Objective:

To assess relapse and MRI activity in patients with multiple sclerosis (PwMS) receiving immune checkpoint inhibitor therapy (ICI). 

Background:

There are reports of disease activity in PwMS receiving ICI. However, this risk is not yet fully understood.

Design/Methods:

In this retrospective cohort study, adult PwMS who received ICI therapy between 2017-2023 were identified using the electronic medical record. Relapses were defined as new neurological symptoms for >24 hours. MRI activity was defined as new T2 or contrast-enhancing lesions. 

Results:

Among 9158 PwMS, 27 PwMS (67% female, median age=64, range=41-79) who received ICI were identified.  MS phenotypes included; primary progressive (2, [9%]), secondary progressive (1, [5%]), relapsing-remitting (17, [81%]) and clinically isolated syndrome (1, [5%]). ICI indications included; melanoma (5, [18%]), lung cancer (12, [44%]), genitourinary carcinoma (5, [18%]), squamous cell carcinoma [tongue, maxillary sinus, anus] (3, [11%]) and gynecologic cancer (2, [8%]). ICIs included; pembrolizumab (15, [55%]), nivolumab (10, [37%]) and durvalumab (2, [7%]). Concurrent disease modifying therapy (DMT) was continued in 11 (40%), including high (7) and low efficacy (4). Median clinical follow-up time was 1.2 years (IQR=0.26-3.5) after ICI treatment. Of 27 patients, 18 had MRI follow-up after ICI with a median radiological follow up of 1 year (IQR=0.22-1.8). Five patients experienced new disease activity; 1 (3.7%) had relapse with new MRI lesions (no DMT, fingolimod paused) and 4 (15%) developed new MRI lesions (no DMT, fingolimod paused [1], ocrelizumab [1], dimethyl fumarate [2]). MS disease activity occurred at a median of 15 days (range 12-226) from the last ICI dose. Seven patients experienced other irAE; Grade 2 (peripheral neuropathy, pneumonitis, colitis, rash), Grade 3 (pneumonitis, colitis) and grade 4 (myasthenia gravis).   

Conclusions:

In this PwMS cohort, clinical relapse after ICI was uncommon. However, asymptomatic new MRI activity was slightly more frequent suggesting a role for MRI monitoring in PwMS receiving ICI.