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Side effect management during immune checkpoint blockade using CTLA-4 and PD-1 antibodies for metastatic melanoma -
Katharina C Kähler1, Jessica C Hassel2, Lucie Heinzerling3
1Department of Dermatology, Venereology and Allergology, University Medical Center of Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Abstract:
CTLA-4 and PD-1 play a key role in tumor-induced downregulation of lymphocytic immune responses. Immune checkpoint inhibitors have been shown to alter the immune response to various cancer types. Anti-CTLA-4 and anti-PD-1 antibodies affect the interaction between tumor, antigen-presenting cells and T lymphocytes. Clinical studies of the anti-CTLA-4 antibody ipilimumab and the anti-PD-1 antibodies nivolumab and pembrolizumab have provided evidence of their positive effects on overall survival in melanoma patients. Combined treatment using ipilimumab and nivolumab has been shown to achieve five-year survival rates of 52 %. Such enhancement of the immune response is inevitably associated with adverse events. Knowledge of the spectrum of side effects is essential, both in terms of prevention and management. Adverse events include colitis, dermatitis, hypophysitis, thyroiditis, hepatitis and other, less common autoimmune phenomena. In recent years, considerable progress has been made in the detection and treatment of the aforementioned immune-related adverse events. However, early diagnosis of rare neurological or cardiac side effects, which may be associated with increased mortality, frequently pose a challenge. The present update highlights our current understanding as well as new insights into the spectrum of side effects associated with checkpoint inhibitors and their management.
Insights
Immune checkpoint inhibitors like anti-CTLA-4 and anti-PD-1 antibodies improve survival in melanoma. However, managing their associated immune-related adverse events is crucial for patient care.
Area of Science:
- Oncology
- Immunology
Background:
- Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) are key regulators of immune responses, often exploited by tumors to suppress anti-tumor immunity.
- Immune checkpoint inhibitors (ICIs) targeting CTLA-4 and PD-1 have revolutionized cancer treatment by restoring T-cell activity against tumors.
Purpose of the Study:
- To review the current understanding and recent advancements in the spectrum of immune-related adverse events (irAEs) associated with anti-CTLA-4 and anti-PD-1 therapies.
- To emphasize the importance of recognizing and managing both common and rare side effects of ICIs.
Main Methods:
- Review of clinical studies and literature on ipilimumab (anti-CTLA-4) and nivolumab/pembrolizumab (anti-PD-1) in melanoma.
- Analysis of reported immune-related adverse events and their management strategies.
Main Results:
- Anti-CTLA-4 and anti-PD-1 therapies, including combination regimens (e.g., ipilimumab plus nivolumab), demonstrate significant improvements in overall survival for melanoma patients, with 5-year survival rates reaching 52% with combination therapy.
- Common irAEs include colitis, dermatitis, hypophysitis, thyroiditis, and hepatitis.
- Rare but potentially fatal irAEs, such as neurological and cardiac events, pose diagnostic challenges.
Conclusions:
- ICIs offer substantial survival benefits in melanoma but are associated with a wide range of irAEs.
- Effective management and early diagnosis of irAEs, especially rare ones, are critical for optimizing patient outcomes and safety during ICI therapy.
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