Immune checkpoint inhibitors: maximizing benefit whilst minimizing toxicity

Area of Science:

• Oncology
• Immunology
• Pharmacology

Background:

• Immunotherapy, specifically immune checkpoint inhibitors (ICI), has transformed cancer treatment, demonstrating efficacy across numerous cancer types.
• Despite durable responses, ICI therapy carries risks of immune-related adverse events (irAEs), with no current FDA-approved biomarkers for predicting patient response or toxicity.
• Understanding and mitigating irAEs is crucial for optimizing cancer immunotherapy outcomes.

Purpose of the Study:

• To synthesize current literature on immune checkpoint inhibitors (ICI) and their associated toxicities (irAEs).
• To review the identification of patients at risk for irAEs, the underlying mechanisms of irAE development, and ongoing biomarker research.
• To examine strategies for irAE prevention and management, including steroid-refractory cases, and highlight future research directions.

Main Methods:

• Comprehensive literature review of clinical studies on ICI and irAEs.
• Synthesis of data on ICI classes, uses, and patient risk stratification for irAEs.
• Analysis of current understanding of irAE pathogenesis and emerging biomarker research.

Main Results:

• ICI therapy offers significant anti-tumor activity but is associated with a spectrum of irAEs.
• Current research is actively investigating biomarkers to predict irAE risk, though a universal predictive tool remains elusive.
• Opportunities for irAE prevention and improved management strategies are emerging, with ongoing clinical trials to establish best practices.

Conclusions:

• While precise irAE risk stratification via biomarkers is challenging, advancements in irAE management and prophylaxis are attainable.
• Ongoing clinical trials are essential for refining prevention and management protocols for immune-related adverse events.
• Optimizing ICI therapy requires a balanced approach, maximizing anti-tumor benefits while proactively addressing irAEs.