Abstract Introduction Pembrolizumab is a human monoclonal antibody directed against programmed death receptor-1 (PD-1), which enhances T-cell mediated activity against cancer cells. However, the immune activation can lead to cross-reactivity within the immune system leading to immune-related adverse effects. We describe a rare case of pembrolizumab-induced Triple-M Syndrome (TMS) — a triad of myasthenia gravis, myocarditis, and myositis — complicated by respiratory failure. Case An 80-year-old male with metastatic renal cell carcinoma receiving adjuvant pembrolizumab presented with progressive dyspnea. Physical examination revealed diplopia, ptosis, dysphagia, and neck weakness notably after receiving his second dose of the immunotherapy. Due to the timeline of the infusion and upper motor neuron signs on examination, concern was raised for immune checkpoint inhibitor related neurologic effects. Symptoms progressively worsened to hypoxic respiratory failure, with a negative inspiratory force noted to be -30. The patient was subsequently intubated and monitored in the intensive care unit. Laboratory studies demonstrated seropositive acetylcholine receptor binding and blocking antibodies, elevated troponins, and elevated creatinine kinase; altogether, confirming myasthenia gravis, myocarditis, and myositis. Cardiac magnetic resonance imaging (cMRI) was obtained showing no myocardial inflammation. The patient underwent plasmapheresis and received intravenous immunoglobulin (IVIG). He also received pulse dose steroids, and was started on ruxolitinib and rituximab with eventual steroid taper. He tolerated the immunotherapy well. While his cardiac and muscular enzymes improved, persistent neuromuscular weakness prevented medical extubation, and a tracheostomy was performed. Discussion TMS is a rare but life-threatening immune checkpoint inhibitor related adverse effect, with a high mortality rate. It involves multiple organ systems and requires rapid recognition and a multi-disciplinary approach for management. Our therapeutic approach involved combining targeted immunosuppressives. Ruxolitinib was used to treat myocarditis as it impairs T-cell activation through the blockade of proinflammatory cytokines and mitigates the high fatality risk. Rituximab was used to deplete B-cells and reduce the antibodies that are contributing to this autoimmune process. Plasmapheresis, intravenous immunoglobulin, and high-dose steroids were also significant in the treatment plan. Cardiac biopsy was discussed, however it was deemed high risk as the patient had baseline complete left bundle branch block. This case represents a successful therapeutic approach to TMS when respiratory failure is most prominent. This abstract is funded by: None
Kaur et al. (Fri,) studied this question.
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