Objective: To describe an early-onset severe case of pembrolizumab-induced Triple M syndrome (myocarditis, myositis, and myasthenia gravis-like disease). This case emphasises the complexity of managing this rare immune-related adverse event, including aggressive immunosuppression, and highlights the clinical pharmacist’s role in optimising care.
Clinical Features: A 77-year-old male with metastatic colorectal adenocarcinoma presented with blurred vision, neck pain, and myalgia four weeks after a single dose of pembrolizumab. Examination revealed bilateral ptosis, diplopia, head-drop neck weakness, proximal limb weakness, and exertion dyspnoea. ECG abnormalities with troponin >1000 ng/L and creatine kinase >4000 U/L raised suspicion for pembrolizumab-induced Triple M syndrome.
Literature review: Only five cases of Triple M syndrome have been reported in the Database of Adverse Events Notifications, supporting that it is a rare life-threatening condition and carries an in-hospital mortality approaching 40%. Evidence supports high-dose corticosteroids for myocarditis, with intravenous immunoglobulin and pyridostigmine for myasthenia gravis. In corticosteroid-refractory disease, second-line immunosuppression may be required, with reports describing abatacept and ruxolitinib use.
Pharmacist Interventions, Case Progress and Outcomes: Initial management included high-dose methylprednisolone pulses followed by oral prednisolone. Intravenous immunoglobulin and mycophenolate were added for clinical deterioration despite biochemical improvement. Escalation to abatacept and ruxolitinib was required via compassionate-access pathways. Pyridostigmine was introduced for persistent ocular symptoms. The pharmacist facilitated medication access via individual patient use pathways, performed dose calculations, ensured infusion safety, screened interactions, monitored for toxicity, recommended antimicrobial prophylaxis, reported the rare adverse event to the Therapeutic Goods Administration, and provided patient education. The patient stabilised and was discharged with a tapering immunosuppression plan.
Discussion: This case highlights Triple M syndrome as a rare but high-risk immune-related adverse event requiring dynamic, individualised management. Pharmacist contributions are integral in bridging these gaps, particularly in facilitating access to emerging therapies and supporting safe immunosuppressive use.