Immune-related adverse events induced by programmed death protein-1 inhibitors from the perspective of lymphoma immunotherapy

Abstract

Lymphoma, which is highly malignant, stems from lymph nodes and lymphoid tissue. Lymphoma cells express programmed death-ligand 1/2 (PD-L1/PD-L2), which binds with programmed cell death 1 protein (PD-1) to establish inhibitory signaling that impedes the normal function of T cells and allows tumor cells to escape immune system surveillance. Recently, immune checkpoint inhibitor immunotherapies such as PD-1 inhibitors (nivolumab and pembrolizumab) have been introduced into the lymphoma treatment algorithm and have shown remarkable clinical efficacy and greatly improve prognosis in lymphoma patients. Accordingly, the number of lymphoma patients who are seeking treatment with PD-1 inhibitors is growing annually, which results in an increasing number of patients developing immune-related adverse events (irAEs). The occurrence of irAEs inevitably affects the benefits provided by immunotherapy, particularly when PD-1 inhibitors are applied. However, the mechanisms and characteristics of irAEs induced by PD-1 inhibitors in lymphoma need further investigation. This review article summarizes the latest research advances in irAEs during treatment of lymphoma with PD-1 inhibitors. A comprehensive understanding of irAEs incurred in immunotherapy can help to achieve better efficacy with PD-1 inhibitors in lymphoma.

Keywords: Lymphoma; Programmed cell death 1 receptor; Immune checkpoint inhibitors; Immune-related adverse events; Nivolumab; Pembrolizumab

Core Tip: Much work on immune checkpoint immunotherapy as cancer therapy has been made in recent years. In lymphoma, the immune checkpoint pathway is used to evade the host immune system and suppress immune cell function. Use of programmed cell death 1 protein (PD-1) inhibitors in lymphoma is supported by their unprecedented clinical efficacy in a range of tumors. Lymphoma patients treated with PD-1 inhibitors inevitably experience immune-related adverse events (irAEs), ranging from mild to life-threatening. Although irAEs can be managed with therapy, severe irAEs may necessitate suspension or even interruption of patient-beneficial PD-1 antibody therapy. It is essential that clinicians take adequate care when irAEs occur.