Editorial: Management of Immune-Related Adverse Events for Patients Undergoing Treatment With Checkpoint Inhibitors

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Treatment With Checkpoint InhibitorsImmunotherapy with immune checkpoint inhibitors has emerged as the most significant advance in the treatment of cancer in recent years and has revolutionized cancer management (1).Until recently, it had been assumed that the immune system was not effective in protecting humans against the development of neoplastic diseases.Checkpoints inhibitors are co-receptors expressed by T cells.These co-receptors regulate T cell activation negatively and play a central role in the maintenance of peripheral self-tolerance.Co-inhibitory receptor ligands are significantly expressed in a variety of malignancies resulting in evasion of anti-cancer immunity.These molecules include programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and were discovered by Tasuku Honjo and James P. Allison in 1992 and 1996, respectively (2, 3).These scientists were jointly awarded the 2018 Nobel Prize for Physiology or Medicine in recognition of this ground-breaking research.Monoclonal antibodies targeting the CTLA-4 and PD-1 and their ligands have produced significant clinical responses against a variety of malignancies (4).FDA registered checkpoint inhibitors include pembrolizumab (5), nivolumab (6), cemiplimab (7), atezolizumab (8), darvolumab (9) and avelumab (10) for numerous indications including melanoma, lung cancer (small and non-small cell types), bladder cancer, Hodgkin's disease and others (5-10).Other co-inhibitory molecules under research include T cell immunoglobulin and mucin domain-containing molecule-3 (TIM-3) (11), Lymphocyte activation gene-3 (LAG-3) (12), V-domain Ig-containing Suppressor of T cell Activation (VISTA) (13), and B-and T-lymphocyte attenuator (BTLA) (14).Treatment with antibodies inhi biting immune checkpoints are well-tolerated by the vast majority of patients and are less toxic compared to standard anticancer chemotherapy agents.These immune side-effects are referred to as immune-related adverse events (IrAE) (15).These toxicities include fatigue, dermatological, gastrointestinal, hepatic, pulmonary, endocrine, ocular, neurological, and rare toxicities such as diabetes, cardiac and hematological.Dermatological toxicities can appear following the first dose of an immune checkpoint inhibitor and can be ongoing.These rashes are frequently maculopapular and mild in nature (16).Rash, and generalized pruritus occur more commonly with CTLA-4 inhibitors compared to anti-PD-1 inhibitors (17).Rare cases of serious skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported (18).The development of vitiligo occurs in a small percentage of patients receiving immunotherapy with checkpoint inhibitors and is associated with long term survival and clinical benefit (19).

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