Biopharmaceutics and Biologic Drugs

Biography

Biography: Arie Regev

Abstract

Immunotherapy is a rapidly developing treatment modality for cancer. Of the broad range of immunotherapies presently in clinical development and clinical use those targeting T cell inhibitor receptors, referred to as “checkpoints”, are the most advanced. They include monoclonal antibodies directed against cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death‑1 (PD-1). Activation of the immune system by inhibiting T-cell checkpoints may cause immune-mediated toxicity, which may be serious and potentially fatal. Abnormal hepatic biochemical tests have been reported in as many as 8% of patients receiving immunotherapy, while clinically significant immune-mediate liver injury has been reported in about 1.5%. In some cases severe liver injury has occurred and cases of acute liver failure leading to death have been reported. Presently there is no reliable method to predict which patients will develop immune-mediated liver injury, and there is no dependable way to identify patients who will develop severe liver injury or liver failure. Although most patients respond to corticosteroid therapy, in some cases additional immunosuppressive agents have been used with varying results. Approaches to monitoring and therapy of such patients are still evolving, and may require studies of large cross-pharma databases, to enable better understanding of the natural history and response to therapy of this potentially lethal complication.