Autoimmune polyneuropathy with severe dysautonomia after ipilimumab treatment for melanoma (P2.109)

Objective: To describe a case of polyneuropathy with dysautonomia after ipilimumab treatment Background: Checkpoint-inhibitor immunotherapies for metastatic melanoma such as ipilimumab can be associated with systemic immune-related Adverse Events (irAE) in 64% of patients. Neurologic events are rare: primarily sensorimotor polyneuropathies in 0.1% in phase II+III trials. Other neurologic irAEs are also reported. Since irAEs are common, dysautonomia can be misdiagnosed. Autonomic neuropathy has rarely been identified with ipilimumab treatment, except for one case of enteric neuropathy diagnosed post-mortem, and 2 cases of acute sensorimotor neuropathy with autonomic symptoms. Design/Methods: Case report of a patient seen at UCLA Medical Center Results: A 63 year old man with melanoma stage IIIc received adjuvant immunotherapy with ipilimumab 10 mg/kg every 3 weeks. On day 23 (after 2 doses of ipilimumab), he went to the ER for back pain. On day 30 he developed abdominal pain, emesis and severe obstipation progressing to ileus, urinary retention and severe orthostatic hypotension. Symptoms were initially attributed to opiate use, urinary tract infection, dehydration, and incidental adrenal lesions. Subsequently it became clear that he had dysautonomia. On day 48, methylprednisolone 48 mg daily was tried without improvement. On day 74 high-dose methylprednisolone 1 gm daily resulted in mild improvement. He was rehospitalized on day 83 for worsening dysautonomia. CSF was acellular with elevated protein, and paraneoplastic panel was negative. He again received methylprednisolone 1 gm for 7 days and IVIG on days 84 and 114, followed by mycophenolate and an extended prednisone taper with clinical improvement. Conclusions: Autonomic neuropathy without sensorimotor symptoms as an irAE of ipilmumab therapy is a challenging diagnosis and has not been reported. Orthostatic hypotension, urinary retention and ileus after immunotherapy should prompt further evaluation for dysautonomia. Lumbar puncture may help in diagnosis. Initial treatment includes high-dose steroids and symptomatic treatment of dysautonomia. Other considerations include IVIG, plasmapharesis, and prolonged systemic immunosuppression. Disclosure: Dr. Kern has nothing to disclose. Dr. Pak has nothing to disclose. Dr. Mazumder has nothing to disclose. Dr. Alegria has nothing to disclose. Dr. Nghiemphu has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Abbvie. Dr. Nghiemphu has received research support from Novartis. Dr. Restrepo has nothing to disclose.