Pharmacokinetics, Pharmacodynamics, and Toxicology Aspects of Immunotherapeutics

Immunotherapy for cancer has been in existence for over a decade demonstrating clinical activity across many tumor types. The increasing understanding of the immune system and its complexity has paved the path for the development of immunotherapy. Immune checkpoint inhibitors (ICIs) are revolutionizing cancer therapy with response rate approaching 50% for monotherapy regardless of tumor type. Combination of ICIs with chemotherapy or other ICIs has been attempted with great success. To further optimize the use of these ICIs, inter-individual variations in exposure and individual response need to be studied. However, potentially severe immune-related adverse events (irAEs) can offset the clinical outcomes of ICI therapy, particularly of combination therapies. The identification, assessment, and management of irAEs require a clear understanding of the pharmacokinetics (PK), exposure–effect relationship, and toxicity profile of these drugs. This chapter provides an overview of the pharmacokinetics (PK), pharmacodynamics (PD), and toxicity of the current immune checkpoint inhibitors as monotherapy and in combination. Collaborative work of basic scientists, clinical pharmacists, and oncologists utilizing advanced technology and artificial intelligence can further enhance the utility of ICIs.