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Acute Inflammatory Demyelinating Polyneuroradiculopathy with Ipilimumab in Metastatic Melanoma: A Case Report and Review of Literature.

ABSTRACT: Ipilimumab (Bristol-Myers Squibb Co., New York, NY) is a novel anticancer medication used for the treatment of metastatic melanoma. The exact mechanism of its action remains unclear; however, data from previous clinical trials postulates the immunomodulatory activity of ipilimumab to enhance therapeutic effectiveness. Ipilimumab was approved by the Food and Drug Administration (FDA) in March 2011 for use in stage III and IV of unresectable metastatic melanoma. We report a single case of acute inflammatory demyelinating polyneuroradiculopthy (AIDP) in the patient treated with ipilimumab for recurrent metastatic melanoma. The patient presented with multiple falls that started after the third infusion of ipilimumab. Other symptoms were hoarseness of voice, motor deficits in his right arms, and tingling in both hands. The deficits progressed into near complete loss of movement and sensation in all four extremities over the course of two weeks. However, his bladder and bowel functions were intact. There was no history of fever, recent travel, exposure to sick contacts, insect bites, or gastrointestinal symptoms. Along with strong immune-mediated pharmacological response towards cancer cells, ipilimumab also induces immune-related adverse events (irAEs) within normal tissues by the mechanism of molecular mimicry.

SUBMITTER: Rupareliya C

PROVIDER: S-EPMC5498115 | biostudies-other | 2017 Jun

REPOSITORIES: biostudies-other

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Project description:The use of immune checkpoint inhibitors including ipilimumab and nivolumab has expanded for several tumors including melanoma brain metastasis. These have resulted in a growing spectrum of neurologic immune-related adverse events, including ones that are rare and difficult to diagnose and treat. Here, we present a patient with melanoma brain metastasis who was treated with immune checkpoint inhibitors and developed an Acute Motor Axonal Neuropathy. To our knowledge, this is the first case of Acute Motor Axonal Neuropathy as an immune-related adverse event associated with combination treatment of ipilimumab and nivolumab, who was successfully treated. A 28-year-old woman with metastatic BRAF V600E melanoma developed melanoma brain metastasis and was enrolled on Checkmate 204, a Phase 2 clinical trial using ipilimumab (3 mg/kg intravenous) and nivolumab (1 mg/kg intravenous) every 3 weeks for four cycles, followed by monotherapy with nivolumab (240 mg intravenous) every 2 weeks. A few days after Cycle 2 of ipilimumab and nivolumab, she developed a pure motor axonal neuropathy consistent with Acute Motor Axonal Neuropathy. She was treated with several immunosuppressive treatments including high dose methylprednisolone, immune globulin, and infliximab, and her motor neuropathy eventually improved several months after onset of symptoms. Unfortunately, she had progression of her systemic disease and died several months later. This is the first case reported of Acute Motor Axonal Neuropathy associated with ipilimumab and nivolumab, successfully treated with immune-suppressive therapy. As the field of immunotherapy expands with the increasing use of the immune checkpoint inhibitors, it is critical to increase our knowledge and understanding of the neurologic immune-related adverse events associated with immune checkpoint inhibitors. This includes the spectrum of rare neurologic immune-related adverse events, which can be quite difficult to recognize and treat. Early consultations with neurology may expedite a diagnosis and treatment plan in patients with unexplained weakness receiving immune checkpoint inhibitor therapy.

Dataset Information

Acute Inflammatory Demyelinating Polyneuroradiculopathy with Ipilimumab in Metastatic Melanoma: A Case Report and Review of Literature.

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