Disclosure(s): No relevant financial relationship(s) to disclose.
First Author: Muhammad Rehan, MD Co-Author: Te Du, MD, PhD – MD, PhD, Virtua Health Co-Author: Rakesh Parchuri, MD – MD, Virtua Health Co-Author: Rasha Abouelsaadate, PharmD, BCCCP – PharmD, BCCCP, Virtua Health Co-Author: Bibek Timilsina, MD – MD, Virtua Health Co-Author: Roman Karagulyan, MD – MD, Virtua Health Co-Author: Abdallah Hussein, MD – MD, Virtua Health Co-Author: Ali Harb, DO – Resident, Virtua Health Co-Author: Monica Patel, DO – Resident, Virtua Health Co-Author: Sriharsha Jammula, MD – MD, Virtuahealth Co-Author: Teja Sureddi, MD – MD, VirtuaHealth Co-Author: Vinay Gadamidi, MD – MD, Virtua Health
Introduction: Immune checkpoint inhibitors (ICIs) have transformed oncology. Dostarlimab is a monoclonal antibody, approved in 2023 for advanced endometrial carcinoma. It binds with programmed death (PD)-1 receptors on T cells and blocks their interaction with programmed death ligands. It demonstrated a safety profile comparable to other anti-PD-1 therapies. We are presenting a rare case of MG crisis as an irAE of dostarlimab.
Description: A 57-year-old lady with stage IIIB1 uterine adenocarcinoma received the first cycle of dostarlimab and 2 weeks later presented with worsening fatigue, dyspnea, and rhabdomyolysis. She developed bilateral ptosis and worsening respiratory status requiring upgrade to the critical care unit and bilevel positive airway pressure with concerns for global neuromuscular (NM) weakness. Workup revealed increased acetylcholine receptor binding antibodies (0.56 nmol/L), suggestive of MG, paraneoplastic, or ICI-induced. She received IV immunoglobulins (IVIG) , oral pyridostigmine, and IV methylprednisolone. Due to refractory MG, rituximab was given, she was transferred to an outside hospital at her request and received plasmapheresis within 48 hours of rituximab. She had 7 sessions of plasma exchange, got intubated for a planned trach after 5 weeks of initial presentation. She had the classic triad of MG, myositis, and myocarditis as an emerging ICI toxicity, received high- dose steroid, transitioned to prednisone with taper, and received atovaquone for prophylaxis. She was discharged to a long-term care facility with a tracheostomy and PEG tube.
Discussion: Our case shows MG an irAE rather than a paraneoplastic syndrome, based on the temporal relationship between the initiation of PD-1 blockade and symptom onset, the absence of tumors associated with paraneoplastic MG, and the increasing evidence linking ICI to NM autoimmune complications. This reflects the importance of early recognizing ICI-induced MG crisis as a cause of acute respiratory failure. Current IVIG and rituximab guidelines recommend against initiating plasmapheresis shortly after administering rituximab; however, literature on the optimal sequence and timing is limited. Early recognition will change the management plan so IVIG and high-dose steroids can be started as soon as the condition is recognized.
