Immune checkpoint inhibitor-related myocarditis, myositis, and myasthenia gravis overlap syndrome: a single-center case series and systematic review.

PURPOSE: The aim of our study was to evaluate the clinical, diagnostic, therapeutic, and prognostic features of immune checkpoint inhibitor-related myocarditis, myositis, and myasthenia gravis overlap syndrome (IM3OS).

METHODS

We conducted a single-center retrospective case series of seven patients with IM3OS treated at Hospital del Mar between 2020 and 2025, together with a systematic review and descriptive patient-level synthesis of the published literature. PubMed/MEDLINE and Embase were searched for reports published between 2015 and 2025, following PRISMA 2020 guidelines. Eligible studies included case reports, case series, letters, correspondence, and conference abstracts providing sufficient individual patient-level data.

RESULTS

In our series, all seven patients were male, with a median age of 81 years. The most frequent tumor types were non-small cell lung cancer (NSCLC) (42.8%) and urothelial carcinoma (28.5%). Diplopia (71.4%), ptosis (71.4%), and dyspnea (71.4%) were the most common presenting manifestations. Most patients received high-dose corticosteroids (71.4%), intravenous immunoglobulins (85.7%), and additional non-steroidal immunosuppressive agents (85.7%). The systematic review included 71 studies and 103 patients. Median age was 71 years, and 68.9% were male. Melanoma (35.9%), renal cell carcinoma (16.5%), and NSCLC (16.5%) were the most frequent malignancies. Ptosis (71.8%) and weakness (62.1%) were the most common presenting symptoms. The most frequently reported initial regimen was methylprednisolone 1 g/day (35.9%), and 52.4% of patients received additional non-steroidal immunosuppressive agents.

CONCLUSION

IM3OS is a rare, early-onset, clinically severe immune-related overlap syndrome with a high mortality rate requiring prompt recognition, structured multisystem assessment, close cardiorespiratory monitoring, and multidisciplinary management. Current evidence remains observational and does not allow conclusions regarding therapeutic superiority.