Chapter 97 - Identification and Management of Checkpoint Inhibition Toxicity

Abstract

Checkpoint inhibitors have revolutionized cancer therapy and the field of oncology when the first drug of this class was introduced for melanoma treatment. But their therapeutic benefit comes at a cost of immunotherapy-related adverse events (IrAEs). Checkpoint inhibitors are immunomodulatory antibodies that are used to activate the immune system to detect and destroy malignant cells. Several immune checkpoint receptors are targeted by different immunotherapy agents, such as cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1), and programmed cell death protein ligand 1 (PD-L1). Immunotherapy agents are currently widely used in patients with hematologic malignancies. Toxicity profiles for these drugs are generally well studied and include dermatologic, gastrointestinal, hepatic, endocrine, hematologic, and other less common complications. It is important to note that at the moment there are no prospective trials on IrAEs management, and all available data are based on clinical experience and retrospective analysis. Although rare, severe and sometimes fatal toxicities may occur with checkpoint inhibitors. Therefore, there is a strong need for predictive biomarkers for IrAEs. Such biomarkers can potentially identify the group of patients who will tolerate immunotherapy. Biomarkers that are being studied include serum proteins, factors in the tumor microenvironment, as well as genomic predictors of toxicity.