Immune checkpoint inhibitors (ICI), such as cytotoxic lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) axis are treatment for several malignancies. Myasthenia gravis (MG) is a rare but life-threatening adverse event of ICI.

With ICI single agent use, 42 cases of new-onset MG are reported in literature, among those, 14 patients developed severe respiratory failure and required intubation whereas 10 patients died. Combination ICI-induced MG was reported in 7 cases, with at least 2 cases complicated by respiratory failure and 1 death. A better outcome was observed in patients who received intravenous immunoglobulin (IVIG) or plasmapheresis (PLEX) as first-line therapy than in those who received steroids alone (95% vs 63% improvement of MG symptoms).

Case 1:
87-year-old woman with stage IV adenocarcinoma of colon received pembrolizumab. Ten days after second dose she presented with worsening new onset bilateral ptosis (left>right) and dysphagia, seropositive with acetylcholine receptor antibodies. There was no significant improvement after a course of IVIG in combination with high dose steroids. A trial of pyridostigmine could not be completed due to symptomatic bradycardia and hospice care was started thirty-eight days after first dose of pembrolizumab.

Case 2:
73-year-old man with metastatic melanoma, received 2 doses of combined ipilimumab and nivolumab. Fifteen days after second dose, he presented with worsening dysphagia, dysarthria, fatigable generalized  weakness and shortness of breath, seronegative for MG antibodies. Symptoms improved dramatically with IVIG. His course was complicated by rostral brainstem ischemic stroke and discharged to hospice ninety-four days after the first dose of combined ipilimumab and nivolumab

Evidence is limited and data from a large cohort of patients is needed to recognize and manage this fatal complication.