The dark side of immunotherapy.

Area of Science:

• Oncology
• Immunology

Background:

• Immunotherapy has revolutionized cancer treatment, offering higher efficacy and lower toxicity than traditional therapies.
• Immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 are highly effective, approved for numerous cancer types, including those with specific genetic markers like MSI-H.
• Despite benefits, immunotherapy can lead to significant adverse events, necessitating comprehensive understanding and management strategies.

Purpose of the Study:

• To review and summarize treatment-related adverse events associated with cancer immunotherapy.
• To identify knowledge gaps in managing immunotherapy-induced toxicities.
• To explore predictive biomarkers for adverse events.

Main Methods:

• A comprehensive literature search of PubMed and Google Scholar databases was conducted up to April 2020.
• Manuscripts evaluating treatment-related adverse events and knowledge gaps of immunotherapy were reviewed.
• Key topics including immune-related adverse events (irAEs), combination toxicities, disease reactivation, hyperprogression, financial toxicity, and special populations were analyzed.

Main Results:

• Immunotherapy, particularly ICIs, is associated with a range of adverse events, including immune-related adverse events (irAEs).
• Specific concerns include toxicities from combination therapies, reactivation of latent infections (e.g., tuberculosis), tumor hyperprogression (HPD), and financial toxicity.
• Challenges exist in managing irAEs in special populations like transplant recipients and patients with autoimmune diseases.
• Worse or lethal outcomes have been reported in certain scenarios compared to other oncologic therapies.
• Biomarkers for predicting adverse events were also summarized.

Conclusions:

• While immunotherapy provides significant benefits in cancer treatment, a thorough understanding of its associated adverse events is crucial.
• Addressing knowledge gaps and identifying predictive biomarkers are essential for optimizing patient safety and outcomes.
• Proactive management strategies are needed to mitigate the risks of irAEs and other treatment-related toxicities.