S3056 Immune-Mediated Hepatitis: A Single Drug or a Class Effect?

Abstract

Introduction: While the rates of diagnosis and death due to non small cell lung cancer are decreasing, the five year relative survival rate remains 20%. Treatment of lung cancer is rapidly evolving, particularly in the metastatic setting. Immunotherapies, most notably PD-1 inhibitors, have drastically changed the landscape of treatment. Immune Hepatitis can, unfortunately, be a reason for discontinuation of the drugs. Immune Hepatitis has been generally thought to be associated with all drugs of a particular class, not specific drug agents. Case Description/Methods: We present a case of an 84 year old female with metastatic non small cell lung cancer with a PD-1 expression of 100%. She was started on single agent Pembrolizumab due to inability to tolerate chemotherapy limiting therapeutic options. Shortly after starting therapy she developed immune hepatitis requiring steroid therapy and withdrawal of the drug with multiple drug interruptions. Ultimately, the drug was discontinued due to worsening elevation in her liver enzymes with resumption of the drug. Standard of practice in such cases is to avoid all drugs in the PD-1 inhibitor family due to similar toxicity profiles and mechanism of action observed. Given the fact that she did not have any other treatment options, she was started on Nivolumab, a different PD-1 inhibitor. Patient was able to tolerate Nivolumab without elevation of her liver enzymes or development of immune hepatitis. She has been on the drug for approximately 10 months with serial monitoring and no evidence of liver injury has been observed. Discussion: While PD-1 inhibitors have revolutionized the treatment of metastatic NSCLC and the drugs are overall well tolerated, a small percentage of patients develop immune mediated liver injury due to reactive cytotoxic T lymphocytes as the reactivated T cells attack other tissues, including the liver. Generally, this has been seen consistently across the entire drug class, not specific to single agents. We present a rare case of immune mediated liver toxicity specific to Pembrolizumab that was subsequently not observed with Nivolumab, despite both drugs having identical mechanisms of actions. Patient has had multiple serial labs and imaging studies showing no progression of her disease, stable on Nivolumab. This case highlights the need for further investigation regarding the mechanism of Immune mediated liver toxicity/injury that may be specific to single agents and not necessarily a drug class.