Background/Case Studies: Immune checkpoint inhibitors (ICIs) are monoclonal antibodies, that inhibit immune checkpoint proteins to generate antitumor immune response but can inadvertently cause immune related adverse events (irAEs). Checkpoint proteins include cytotoxic T lymphocyte associated protein 4 (CTLA-4) on the surface of T cells and programmed cell death 1 (PD-1) on T cells, B cells and NK cells. Among the irAEs, only few cases of myasthenia gravis associated with ICIs (MG-ICI) have been described and there is insufficient data to support the role of therapeutic plasma exchange (TPE), per ASFA guidelines (category III). Although irAEs are not uncommon with ICIs, fatalities are rare. We report a case of MG-ICI and unsuccessful treatment with TPE.
Study
Design/Methods: A 61-year-old male with recurrent cutaneous melanoma of posterior scalp, status post 2 cycles of neoadjuvant ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) for recurrent metastatic posterior cervical lymphadenopathy, gout, arthritis and deep vein thrombosis (on warfarin) presented with acute diplopia 3 days following cycle 2 of ICIs. Imaging was unremarkable and CSF studies were non-contributory. Acetylcholine receptor antibodies (anti-Ach, binding, blocking and modulating) resulted positive and muscle specific kinase antibodies (anti-MuSK) were negative. MG-ICI was considered, and dexamethasone was initiated. Chest CT was negative for thymoma. After having to discontinue pyridostigmine due to diarrhea, worsening weakness and acute respiratory distress requiring intubation, patient was admitted in ICU through ED. Five IVIG infusions were administered and the patient was extubated. However, he developed increasing respiratory distress and 5 days later, required reintubation. After apheresis medicine consultation, a decision to initiate a series of TPE was made.
Results/Findings: After 5 TPE procedures, extubation was attempted but remained unsuccessful, causing stridor due to likely oral secretions, and requiring reintubation again. Pyridostigmine dose was decreased due to significant oral secretions. Despite weaning sedation and a decrease in pre-procedure anti-Ach level (Figure A), the patient continued to have severe bilateral ptosis. Three additional TPE procedures were performed. Each TPE involved 1.0 plasma volume exchange using 5% albumin as replacement fluid. In accordance with the patient’s previously expressed wishes per family, the patient was made comfort measures only (CMO) in case of continuing clinical deterioration, without further reintubation. After 8 TPE procedures, the patient was extubated and transitioned to BiPAP but passed away later that day.
Conclusions: Limited data exists about MG-ICI and its management. The role of TPE in the management of severe cases is uncertain. Further studies are needed to determine successful modes of treatment.
