A systematic review and meta-analysis published in the European Journal of Neurology in 2025 has examined the impact of immune checkpoint inhibitors (ICIs) on multiple sclerosis (MS) disease activity. The study aimed to synthesize the current evidence regarding the potential effects of ICI treatment on MS course, addressing an important knowledge gap as the use of these cancer therapies increases among MS patients.
The research team conducted a comprehensive literature search following PRISMA 2020 guidelines, identifying five observational studies that met their inclusion criteria. These studies, published up to early May 2024, provided data on clinical and neuroradiological outcomes in MS patients treated with ICIs for various malignancies.
For the analysis of clinical disease activity, the meta-analysis included a pooled cohort of 90 MS patients with a total follow-up of 103.74 patient-years. The mean age of patients ranged from 48 to 67.4 years, with disease durations spanning 10 to 26.8 years. The most common malignancies treated were melanoma (45%) and lung cancer (33.3%).
The results showed a pooled relapse rate of 5.45 per 100 patient-years (95% CI: 1.86-14.92) following ICI treatment. Importantly, no relapses were observed in patients over 58 years of age, suggesting a potential protective effect of age against ICI-induced disease activity. The study also found that 60% of patients experiencing a relapse were not on disease-modifying therapy (DMT) at ICI initiation, indicating a possible protective role of DMT against ICI-induced relapses.
Regarding MRI disease activity, the analysis included 36 MS patients with a total of 41.94 patient-years of follow-up. The pooled rate of new MRI lesions was 24.9 per 100 patient-years (95% CI: 10.9-47.3). However, this higher rate of neuroradiological activity should be interpreted cautiously, as 80% of patients with new MRI lesions had suspended DMT at ICI initiation, potentially leading to an overestimation of the event rate.
A key finding was that all disease activity events, both clinical and neuroradiological, occurred within the first 6 months of ICI treatment. This observation highlights the importance of close monitoring during the initial months of ICI administration in MS patients.
The study has several limitations, including the small number of available studies, their retrospective nature, and potential treatment selection bias. The inclusion of a pre-print study accounting for a large portion of the patients may also introduce bias. Additionally, the complete absence of data on the potential impact of ICIs on disease progression is a significant limitation.
Despite these limitations, the authors conclude that ICI administration in MS patients with cancer results in a low and manageable risk of relapse. They suggest that the use of ICIs should be considered in MS patients given their significant prognostic impact on malignancies. To minimize the risk of disease reactivation, the authors recommend continuing DMT during ICI administration and implementing intensive monitoring of disease activity during the first 6 months of treatment.
The potential clinical impact of this study is significant, as it provides valuable guidance for neurologists and oncologists managing MS patients who require ICI treatment for cancer. The findings suggest that ICIs can be used with relative safety in this population, particularly when appropriate precautions are taken. However, the authors emphasize the need for larger, multicentric, long-term, prospective studies to more accurately estimate the risk of disease activity and provide data on the potential impact on future disease progression.
This meta-analysis represents an important step in understanding the intersection of MS management and cancer immunotherapy. As the MS population ages and the use of ICIs becomes more widespread, this research provides a foundation for evidence-based decision-making in clinical practice. However, it also underscores the need for continued research to refine our understanding of the long-term impacts of ICI treatment on MS disease course.
References
Gelibter S, Saraceno L, Susani E, Pirro F, Sessa M, Protti A. Do immune checkpoint inhibitors affect the course of multiple sclerosis? A systematic review and meta-analysis. Eur J Neurol. 2025;32(1):e16547. doi:10.1111/ene.16547
