We describe a clinical case illustrating the need for standardized treatment protocols for fulminant ICI-induced Triple M syndrome.
ICI-induced Triple-M syndrome is characterized by concurrent immune-mediated myositis, myocarditis, and myasthenia gravis and is an ominous adverse effect. Initial management involves steroids, but consensus guidelines for further treatment with agents like abatacept and ruxolitinib have not been established.
A 68-year-old male with history of esophageal adenocarcinoma after four cycles of FLOT (fluorouracil, leucovorin, oxaliplatin, docetaxel) and durvalumab presented for worsening diplopia and dyspnea on exertion. He was found to have elevated troponin and creatine kinase concerning for ICI-induced myocarditis and myositis. Neurology evaluated the patient for bilateral ptosis/fatigable dysphonia with respiratory distress and diagnosed ICI-induced myasthenia with positive AChR blocking and binding antibodies. He was treated with high-dose IV methylprednisolone on day 1 with daily pyridostigmine but soon required abatacept initiation on days 3-4. Despite the combined regimen, he continued to clinically worsen and required PLEX for 5 days starting on day 4 followed by IVIG for five days starting on day 15. Abatacept was again administered on days 16 & 30. NIFs continued to worsen requiring intubation on day 33 with repeat IVIG on days 34-35. Given the overall worsening course, ruxolitinib was initiated on day 37 with limited up-titration. Despite therapy, the patient required a tracheostomy with eventual discharge to long term rehab.
ICI induced Triple-M syndrome is a feared adverse effect with high mortality rates. Given the patient's respiratory and neurologic decline despite acute immunotherapies and abatacept, ruxolitinib was administered though later in the clinical course. This case demonstrates not only the importance of recognizing Triple-M syndrome following immune-checkpoint inhibitor therapy but also the need for standardized treatment protocols including early multimodal therapy.