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Immune Checkpoint Inhibitor Toxicity
David J Palmieri1, Matteo S Carlino2,3,4
1Crown Princess Mary Cancer Centre, Westmead Hospital, Corner Hawkesbury & Darcy Roads, Westmead, NSW, 2145, Australia.
Purpose Of Review:
Immune checkpoint inhibitors have revolutionised the treatment of multiple malignancies and have a growing list of indications. As our familiarity with these agents grows, so does our understanding of their unique spectrum of toxicities. Here, we will review the literature regarding the toxicities of checkpoint inhibitors and address challenges encountered in day-to-day clinical practice.
Recent Findings:
Inhibitors of the PD-1/PD-L1 axis are considerably less toxic than the anti-CTLA-4 antibody ipilimumab. The combination of ipilimumab and anti-PD-1 agents is being trialled in multiple malignancies and is associated with increased toxicity. There is accumulating evidence suggesting a potential correlation between a subset of toxicities and clinical benefit in several tumour types, although conflicting data exists. Retrospective series have shown that anti-PD-1 can be safely administered to patients with prior high-grade toxicity from ipilimumab or combination immunotherapy. The management of checkpoint inhibitor toxicity is complex and requires collaboration with our subspecialty colleagues. Identifying predictive biomarkers of both efficacy and toxicity would likely help guide treatment decisions, and should be a research priority in the years ahead.
Insights
Immune checkpoint inhibitors offer new cancer treatments but have unique toxicities. Managing these side effects requires collaboration and research into biomarkers for better treatment decisions.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Immune checkpoint inhibitors (ICIs) have transformed cancer therapy across numerous malignancies.
- Understanding the specific toxicities associated with ICIs is crucial for effective clinical management.
Purpose of the Study:
- To review the existing literature on the toxicities of immune checkpoint inhibitors.
- To address the practical challenges faced in the daily clinical application of these therapies.
Main Methods:
- Literature review of toxicities associated with PD-1/PD-L1 axis inhibitors and anti-CTLA-4 antibody (ipilimumab).
- Analysis of clinical trial data and retrospective series regarding combination immunotherapy and management of prior toxicities.
Main Results:
- PD-1/PD-L1 inhibitors generally exhibit lower toxicity compared to ipilimumab.
- Combination therapy with ipilimumab and anti-PD-1 agents is linked to increased toxicity.
- Evidence suggests a potential correlation between certain toxicities and clinical benefit, though data are conflicting.
- Anti-PD-1 agents can be safely used in patients with prior high-grade toxicity from ipilimumab or combination immunotherapy.
Conclusions:
- Management of ICI toxicity is complex, necessitating multidisciplinary collaboration.
- Identifying predictive biomarkers for both efficacy and toxicity is a critical research priority to guide treatment decisions.
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