Esophageal Achalasia Induced by Ipilimumab and Nivolumab Combination: A Rare Neurological Manifestation of Immune-related Autonomic Neuropathy.

Immunotherapy with immune checkpoint inhibitors (ICIs) has improved the prognosis of many cancers; a combination of nivolumab (anti-programmed cell death protein 1) and ipilimumab (anti-cytotoxic T-lymphocyte-associated protein 4) is approved as first-line therapy for advanced melanoma, with objective responses obtained in more than half of patients. However, this combination is associated with a high rate of immune-related adverse events, which are often severe and multiple. Neurological immune-related adverse events are rare but feared because they can be life-threatening, their diagnosis and management are challenging, and patients can have irreversible sequelae. We reported a case of a young patient treated by nivolumab and ipilimumab combination for metastatic melanoma. Severe dysphagia with regurgitations, major weight loss, uveitis, and vitiligo occurred after 3 infusions of nivolumab and ipilimumab. Magnetic resonance imaging and positron emission tomography scan showed complete remission of melanoma. The endoscopic examination did not find any digestive toxicity. Esophageal manometry revealed achalasia. This was associated with mydriasis, pathologic deep breath test, and alteration of the cutaneous sympathetic response on electromyogram, which was consistent with autonomic neuropathy. This rare etiology of atypical vomiting under ICI should be known by prescribers, as ICI prescription is widening in many new cancers.