Immune-Related Adverse Events: A Case-Based Approach

Abstract

Immunotherapy has heralded the advent of a new era in oncology. Immune checkpoint inhibitors (ICIs) enhance anti-tumor immunity, thereby reinvigorating a patient's immune system to fight cancer. While therapy with this class of agents has resulted in improved clinical outcomes for patients with multiple tumor types, a broad spectrum of immune-related adverse events (irAEs) may affect any organ system, with variable clinical presentations. Prompt recognition and management of irAEs are associated with improved irAE outcomes, and represents an important new clinical challenge for practicing oncologists. Herein, we provide a comprehensive case-based review of the most common and clinically-important irAEs, focussing on epidemiology, clinical manifestations, and management. We also examine future strategies that may provide meaningful insights into the prevention and management of irAEs.

Analysis of immune‐related adverse events caused by immune checkpoint inhibitors using the Japanese Adverse Drug Event Report database

“…For example, the clinical guidelines of Japan Endocrine Society indicate the classifications of irAE in the endocrine region. 19 Other reviews and papers 3,6,9,11 listed other irAEs such as colitis, hyperthyroidism, and hypothyroidism. Furthermore, the research using the SRS database focuses on myasthenia gravis, 14 and myocarditis.…”

“…13 Using the FAERS database, Ji et al 10 comprehensively evaluated AE profiles, including irAEs using Standardized MedDRA Queries 20 that consist of PTs grouped according to the level that relates to a defined medical condition. Based on previous reports, 3,6,[9][10][11]13,14,19,21 we categorized irAEs into the following 14 groups: adrenal insufficiency, colitis, eye disease, hematological disorder, hepatitis, hyperthyroidism, hypopituitarism, hypothyroidism, myasthenia gravis, myocarditis, nephritis/renal dysfunction, pneumonitis, rash, and type 1 diabetes mellitus and selected PTs for each category (Table 1).…”

“…1 Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that act against cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed cell death protein (PD-1), and its ligand PD-L1 to eliminate cancer cells and restore immune control. [1][2][3] ICIs are one of the most important breakthroughs in cancer treatment, 4 but are associated with a spectrum of drug-related autoimmune disorders and inflammatory diseases known as immunerelated adverse events (irAEs). 5,6 These irAEs represent a serious clinical problem during treatment with ICIs.…”

“…8 Thus, all potential irAEs should be brought to the attention of healthcare professionals in a timely manner because early intervention can prevent progression and permanent damage. 3,9 The symptoms and progression of irAEs are different from those of adverse events (AEs) caused by conventional anticancer agents. 6 irAEs may affect any organ or system such as the colon (colitis), eye disease, hematological disorder, liver (hepatitis), nervous system (myasthenia gravis), heart (myocarditis), kidneys (renal dysfunction), lungs (pneumonitis), skin (rash), and endocrine system (adrenal insufficiency, hypopituitarism, thyroiditis, diabetes mellitus).…”

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“…The cause of irAEs is thought to be related to the aberrant action of activated T cells. Several possible mechanisms behind irAEs include: 1) Exacerbation of subclinical inflammation by ICI, 74 2) crossreactivity of shared antigens between organs at risk and tumors, [77][78][79] and 3) the negative impact of ICI on the gut microbiome. 80,81 Early fears for clinicians using immunosuppression for treatment of irAEs were grounded in the fact irAEs were correlated with improvement in PFS, OS, and ORR, a phenomenon that was more notable in anti-PD -1/PD-L1 than anti-CTLA4 agents.…”