Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies

Abstract

Immune checkpoint antibodies that augment the programmed cell death protein 1 (PD-1)/PD-L1 pathway have demonstrated antitumor activity across multiple malignancies, and gained recent regulatory approval as single-agent therapy for the treatment of metastatic malignant melanoma and nonsmall-cell lung cancer. Knowledge of toxicities associated with PD-1/PD-L1 blockade, as well as effective management algorithms for these toxicities, is pivotal in order to optimize clinical efficacy and safety. In this article, we review selected published and presented clinical studies investigating single-agent anti-PD-1/PD-L1 therapy and trials of combination approaches with other standard anticancer therapies, in multiple tumor types. We summarize the key adverse events reported in these studies and their management algorithms.

Keywords: adverse event; anti-PD-1; anti-PD-L1; immune checkpoint antibody; toxicity.

Figure 1.

Adapted management algorithm for skin rash with immune checkpoint blockade. *BSA, body surface area, **Symptoms as per CTCAE version 4.0. For example: pruritus, burning and skin tightness. ^$Additional supportive measures: this denotes the use of, for example, prophylatic antibiotics and management in the burns unit.

Figure 2.

Adapted management algorithm for hepatitis with immune checkpoint blockade. *ULN, upper limit of normal.

Figure 3.

Adapted management algorithm for pneumonitis with immune checkpoint blockade.