PD-1 checkpoint inhibition: Toxicities and management

Abstract

Purpose: With the recent approval of 5 PD-1/PD-L1 inhibitors for a number of malignancies, PD-1 axis inhibition is drastically changing the treatment landscape of immunotherapy in cancer. As PD-1/PD-L1 are involved in peripheral immune tolerance, inhibition of this immune checkpoint has led to novel immune-related adverse events including colitis, hepatitis, pneumonitis, rash, and endocrinopathies among many others.

Materials and methods: In this seminar, we will analyze the incidence of immune-related adverse events for nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab. Then, we will discuss the specific management of the most common immune-mediated adverse events including colitis, hepatitis, pneumonitis, rash, endocrinopathies, nephritis, and neurologic toxicities.

Results: Immune-related adverse events are frequently treated with immunosuppressive medication such as steroids and mycofenolate mofetil.

Conclusions: There are specific immune-related adverse events which are frequently seen by the treating oncologist from checkpoint inhibitors. It is essential to understand the recommended treatment options to minimize toxicity and mortality from this important class of anti-neoplastic therapies.

Keywords: Atezolizumab; Avelumab; Durvalumab; Immune-related adverse events; Management; Nivolumab; PD-1 inhibitor; PD-L1 inhibitor; Pembrolizumab; Treatment.