2480 Nivolumab-Induced Hepatitis and Vesiculopustular Skin Rash in a Patient With Metastatic Melanoma

Abstract

INTRODUCTION: The advent of immunotherapy has been hailed as a breakthrough in cancer treatment. However, it comes with a multitude of immune mediated adverse effects. Gastrointestinal adverse effects include hepatitis and colitis. Immunotherapy related hepatitis can range from asymptomatic elevation of liver enzymes (grade 1) to decompensated liver failure (grade 4). CASE DESCRIPTION/METHODS: 82 years old male with stage IIC Malignant Melanoma of right posterior diagnosed in 2014, treated with wide excision. In December 2016, PET scan revealed right chest wall lesion, treated with re-excision. c-kit and BRAF were negative. In June 2017, PET scan showed metastatic disease involving lung, pancreas, gluteus maximus and left flank. The patient was started on Nivolumab. After 7 cycles, the PET scan became negative for any metastatic lesions. After 8 cycles, he had a severe morbilliform, vesiculopustular rash secondary to Nivolumab. Skin Biopsy showed a lymphocytic infiltrate with scattered eosinophils and numerous neutrophils. High dose prednisone was started with tapering for 3 months. Nivolumab was temporarily held and resumed after a good response to steroids. After 14 cycles, the patient developed malaise, fatigue, nausea and mild abdominal pain. ALT was 393, AST 302, ALK 164. Bilirubin was 1.1. Hepatitis A, B, and C testing were negative, anti-liver kidney microsomal antibody and anti-mitochondrial antibody was negative, acetaminophen level was normal, CT and Ultrasound of the liver were negative for metastatic lesions or other hepatic pathology. No recent change in medication or alcohol use was reported. As per ASCO guidelines, hepatitis was classified as Grade III (ALT and AST >5-20 times the upper limit of normal). The patient was started on 100 mg prednisone daily with tapering for 2 months. Liver enzymes normalized and symptoms resolved. Nivolumab was discontinued. PET scan 6 months from the last cycle showed disease in remission. DISCUSSION: Treatment of immunotherapy induced hepatitis depends on severity. Immunotherapy can be continued in grade 1, temporarily held in grade 2, and permanently discontinued in grade 3 and 4 as per guidelines. High dose steroids (prednisone 1-2 mg/kg) with tapering serve as the mainstay of treatment. Mycophenolate or azathioprine can be considered in refractory cases. However, it needs further research whether immunotherapy can be re-trialed in patients with grade 3 toxicity, who have responded well to the steroids, and would potentially benefit from a repeat trial.