Use of rituximab for fulminant and refractory cases of immune checkpoint inhibitor induced myocyte injury clinically presenting with features of myasthenia gravis: a case series.

[BACKGROUND] Immune checkpoint inhibitor-related overlap syndromes are serious and potentially life-threatening complications of immunotherapy. The available evidence is scarce to guide treatment for refractory cases, and patients often experience poorer outcomes.

[CASE SUMMARY] We describe two patients who presented with non-specific symptoms of fatigue and weakness. Both exhibited biomarker evidence of skeletal muscle and myocardial injury, along with clinical features suggestive of myasthenia gravis. The patients rapidly deteriorated, requiring admission to the intensive care unit and eventual intubation due to worsening respiratory status. Despite treatment with high-dose intravenous steroids, there was no significant clinical improvement, although early reductions in biomarker levels were observed. This led to the administration of additional therapies, including intravenous immunoglobulin and plasmapheresis, but these interventions were also ultimately ineffective. All testing for myasthenia gravis returned negative, highlighting how patients with primary myositis or overlap myositis with myocarditis can present with bulbar symptoms that closely mimic those of myasthenia gravis. Following multidisciplinary discussions, rituximab was initiated in both cases, which led to successful weaning from mechanical ventilation and eventual discharge.

[DISCUSSION] Our case series highlights how patients with primary myositis or overlap myositis with myocarditis may present with bulbar symptoms that can mimic those of myasthenia gravis. Their clinical course was refractory to initial treatments but improved significantly with rituximab. While current guidelines typically recommend biologic therapies targeting T-cell-mediated immunity, our review of literature found a biological basis for targeting antibody-mediated immunity as well. This approach proved effective, enabling both patients to achieve successful discharge after a prolonged and complex hospitalization, highlighting the importance of considering treatment directed at both T-cell and B-cell immunity.