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.
IM3OS predominantly affected older males in both the single-center series and systematic review.
The most common tumor types in the single-center series were non-small cell lung cancer and urothelial carcinoma.
Diplopia, ptosis, and dyspnea were the most common presenting manifestations in the single-center series, while ptosis and weakness predominated in the systematic review.
Most patients in both the single-center series and systematic review required high-dose corticosteroids and additional immunosuppressive agents.
The systematic review identified 71 studies encompassing 103 patients with IM3OS published between 2015 and 2025.
IM3OS carries a high mortality rate and is characterized as a rare, early-onset, and clinically severe immune-related overlap syndrome.
This research suggests that when cancer patients receiving immune checkpoint inhibitor therapy (a modern form of immunotherapy) develop a simultaneous combination of three serious immune-related side effects—heart muscle inflammation (myocarditis), skeletal muscle inflammation (myositis), and a neuromuscular weakness disorder (myasthenia gravis)—the resulting condition, called IM3OS, is extremely dangerous. The study combined findings from seven patients treated at a single Spanish hospital with a review of 103 additional cases reported in the medical literature over the past decade. Patients were predominantly older males, and the most common early warning signs included drooping eyelids, double vision, and shortness of breath. Treatment typically required aggressive immunosuppression, including high-dose steroids and intravenous immunoglobulins, with most patients also needing additional immune-suppressing medications. Despite this intensive treatment, the syndrome carries a high death rate. The tumors most commonly associated with this syndrome in the broader literature were melanoma, kidney cancer, and lung cancer, while the single-center experience highlighted lung and bladder cancers. This research suggests that oncology teams need to be vigilant about recognizing this rare but life-threatening combination of side effects early, as it requires coordinated care from multiple medical specialties including cardiology, neurology, and oncology. The authors note that because all available evidence comes from individual case reports rather than clinical trials, it is not yet possible to determine which treatment approach works best, underscoring the need for prospective research and standardized reporting of this overlap syndrome.
Soriano J, Martínez-Rubiño M, Vicente Elcano M, Pellicer Pérez M, Bergua de Roque A, Tanco Mulero S, et al.. (2026). Immune checkpoint inhibitor-related myocarditis, myositis, and myasthenia gravis overlap syndrome: a single-center case series and systematic review.. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. https://doi.org/10.1007/s00520-026-11363-w