Management of TripleM Syndrome: A Systematic Review with Narrative Synthesis of Immune Checkpoint Inhibitor-Induced Myasthenia Gravis, Myositis and Myocarditis.

Background

The advent of immunotherapy has revolutionised cancer treatment by harnessing the immune system to target tumour cells. However, there is increasing awareness of immunotherapy-related adverse events, which can be severe and even fatal. While system-specific immune-related adverse events (ir-AEs) are well documented, growing evidence suggests the existence of overlap syndromes-distinct clusters of immune-mediated complications. One such syndrome is the overlap of myasthenia gravis, myositis and myocarditis, collectively known as Triple M (3M) syndrome. This syndrome is complex, varying in presentation and severity, with in-hospital mortality rates approaching 40%. Whilst there is consensus on the management of system-specific complications, there is no consensus guidance for the management of these overlap syndromes.

Methods

In this paper, we conduct a review of the literature, analysing reported cases of 3M syndrome, focusing on treatment approaches and patient outcomes at an individual level.

Conclusions

This review highlights the complexity of diagnosing and managing 3M syndrome due to inconsistent reporting, lack of standardised criteria for diagnosis, and treatment variability. While evidence remains limited, we offer broad clinical recommendations and underscore the urgent need for consensus definitions, prospective data collection, and structured treatment guidance.