Background
Immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs). Patients with autoimmune diseases, such as multiple sclerosis (MS), might have an increased risk of irAEs. This study aims to investigate the risk of MS relapses and other irAEs in MS patients treated with ICIs.
Methods
This single-center retrospective study was conducted by electronically identifying MS patients receiving ICIs for solid-organ malignancy treatment at UH Seidman Cancer Center from inception to May 2024. We obtained information about outcomes after ICIs initiation including MS relapses, irAEs, and survival outcomes.
Results
We identified 12 patients with a median age (range) of 62.2 (35.9, 77.9) years (table 1). Indications for ICIs included non-small cell carcinoma (stage IIB, III, and IV, 50%), small cell carcinoma (stage IV, 16.7%), breast adenocarcinoma (stage IIA and IV, 16.7%), esophageal carcinoma (stage IV, 8.3%), and melanoma (stage IIIB, 8.3%). The agents used were Pembrolizumab (66.7%), Atezolizumab (16.7%), and Durvalumab (16.7%). The median follow-up time was 14.7 (0.6, 40.2) months and the median number of cycles of ICIs given was 7 (1, 17). All but one patients had relapsing-remitting MS (91.7%). At the time of ICI initiation, no patients had active MS lesions and 4 patients (33.3%) were on MS disease-modifying treatments (DMTs), including dimethyl fumarate/Tecfidera (16.7%), glatiramer acetate/Copaxone (8.3%), and interferon beta-1a/Avonex (8.3%). No patients had an MS relapse; including after termination. Two patients (16.7%) developed grade III-IV irAEs, both were pneumonitis, which occurred after 1–2 cycles and were treated with intravenous steroids. ICIs were not resumed and the time to next therapy (mean±SD) was 1.0±0.5 months. Overall, 2 patients died (16.7%, from pulmonary embolism and an unknown cause) and the responses to ICIs were complete response (8.3%), partial response (75%), and progressive disease (2%). Median treatment-free survival was 3.9 (0.6, 39.1) months and the durable response rate was 41.7%. Interestingly, for every additional year of age, the risk of disease progression decreased by 10% (hazard ratio (HR) 0.897 with 95% confidence interval (CI): 0.823–0.976, p=0.0120) and the risk of having irAE decreased by 14% (HR 0.858, 95%CI: 0.798–0.922, p<.0001). There was no significant difference in overall survival, progression-free survival, or the risk of irAE between patients with and without MS DMTs.
Conclusions
Our study suggests that ICI use were not associated with MS relapse. Although larger studies are required for more accurate risk assessment, ICIs should be considered for cancer treatment in MS patients.
Ethics Approval
This study was approved by the Institutional Review Board at University Hospitals. The ID of the approval was STUDY20221434 with the parent study’s full title of ‘Immunotherapy at UH: A Database for System Wide Evaluation of Response, Adverse Events for Study’. No participant informed consent was required for the study.
Abstract 473 Table 1
Demographic characteristics