Pre-existing Lambert-Eaton Myasthenic Syndrome and Scleroderma in a Patient with Neuroendocrine Tumor undergoing Immune Checkpoint Inhibitor Cancer Immunotherapy (P4-5.029)

Objective: To illustrate the diagnostic and therapeutic challenges regarding paraneoplastic Lambert-Eaton Myasthenic Syndrome (LEMS) in patients with malignancy on immune checkpoint inhibitor (ICI). Background: Paraneoplastic syndromes often co-exist and can worsen with ICI cancer immunotherapy. Design/Methods: Case report. Results: We report a case of a 66-year-old female with progressive weakness and dry eyes and mouth diagnosed with LEMS based on P/Qtype voltage-gated calcium channel (VGCC) antibody positivity (0.11 nmol/L initially). She was diagnosed with neuroendocrine tumor and treated with weekly IVIg, chemotherapy (carboplatin and etoposide) and radiation with some improvement. A year into her disease she developed Raynaud’s and tightness of her fingers, legs, back and skin compatible with scleroderma with RNA Polymerase III antibody positivity. Due to cancer progression, she was treated with ICIs (ipilimumab and nivolumab) with concomitant IVIg. Due to colitis and thyroiditis, ipilimumab was discontinued. She was stable for eight months but then developed progressive weakness, dropped head, dysphagia and increased shortness of breath. Two hertz repetitive nerve stimulation of the ulnar and spinal accessory nerve demonstrated facilitation of 223% and 128% respectively after a baseline decrement, confirming a presynaptic disorder of the neuromuscular junction with diffuse myopathic changes without fibrillation potentials on electromyography. Repeat P/Q-type-VGCC-IgG was 0.89 nmol/L; creatinine kinase levels were normal. Nivolumab was stopped, and she was treated with 3,4-diaminopyridine and weekly IVIg; corticosteroid use was limited by her scleroderma, and plasma exchange due to infection. The patient had cancer progression and died within three weeks. Conclusions: This patient with pre-existing paraneoplastic LEMS and scleroderma was stable for 8 months while on ICI. Her clinical presentation upon progression with dropped head could be related to LEMS with secondary myopathic change or an ICI-triggered-myopathy. This patient illustrates the complexity of therapeutic decision making in these patients and the necessity of a multidisciplinary approach. Disclosure: Dr. Vorasoot has nothing to disclose. Dr. Halfdanarson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TerSera. Dr. Halfdanarson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Terumo. The institution of Dr. Halfdanarson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ipsen. The institution of Dr. Halfdanarson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Advanced Accelerator Applications. The institution of Dr. Halfdanarson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Isotopen Technologien Muenchen (ITM). The institution of Dr. Halfdanarson has received research support from Advanced Accelerator Applications. The institution of Dr. Halfdanarson has received research support from Thermo-Fisher Scientific. The institution of Dr. Halfdanarson has received research support from Camurus. Dr. Madigan has nothing to disclose. Dr. Thanarajasingam has nothing to disclose. The institution of Dr. Zekeridou has received research support from Roche/Genentech. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care.