Rare Adverse Events with Programmed Death-1 and Programmed Death-Ligand 1 Inhibitors: Justification and Rationale for a Systematic Review

Abstract

Purpose

Immune checkpoint inhibitors are a new class of cancer drug that spawn unusual adverse events that generate unusual and sometimes unexpected adverse events. Despite databases that track such adverse events, there remains a need to also generate systematic reviews to capture side effects from such agents.

Findings

We generated a systematic compendium of adverse event reports. Extensively reviewing the published literature of case reports and case series, we relied on the peer process to compile a resource for clinicians of rare adverse events associated with checkpoint inhibitors. We used this compendium as a platform to provide broad-based comments on the role of systematic reviews in gathering such adverse event data. This approach generated 265 types of rare adverse events that had been reported, the most frequent of which were autoimmune type I diabetes (n = 62), pneumonitis (n = 40), myocarditis (n = 39), and colitis (n = 36). More unusual adverse events were also catalogued. Some adverse events that initially seemed unusual turned out to be more frequently reported over time and thus lost their novelty—an important point which provides context for how adverse events should be viewed when new drugs become available. Additionally, in contrast to such resources as the FDA Adverse Event Reporting System (FAERS), this systematic review relied on peer-reviewed data—another important point which adds strength to such systematic reviews.

Summary

This report provides a compendium of rare and usual adverse events, serves as a resource to cancer clinicians, and appears to be justified based on the reported findings.