Programmed cell death-1 pathway inhibitors in genitourinary malignancies: specific side-effects and their management

Area of Science:

• Oncology
• Immunology
• Pharmacology

Background:

• Immune checkpoint inhibitors (ICIs), particularly those targeting the programmed cell death (PD)-1 pathway, have revolutionized cancer treatment.
• These agents harness the host immune system to generate an antitumor response, leading to approvals in genitourinary cancers like renal cell carcinoma and urothelial carcinoma.

Purpose of the Study:

• This review focuses on the management of toxicities associated with immune checkpoint inhibitors.
• It aims to provide guidance on recognizing and mitigating immune-related adverse events (irAEs).

Main Methods:

• Review of current literature on PD-1 pathway inhibitors and their associated toxicities.
• Analysis of management strategies for immune-related adverse events.

Main Results:

• While generally well-tolerated, 10-20% of patients on PD-1 monotherapy experience severe autoimmune manifestations (irAEs).
• Common irAEs include rashes, pneumonitis, endocrinopathy, colitis, and hepatic dysfunction.
• Combination therapy with anti-CTLA-4 antibodies (e.g., ipilimumab) increases irAE incidence.
• Early immunosuppression with corticosteroids can mitigate irAEs without compromising efficacy.

Conclusions:

• Immune checkpoint inhibitors represent a significant advance in cancer therapy.
• Effective management of irAEs through early recognition and aggressive treatment is essential for safe clinical application.
• Proactive management ensures the continued benefit of these immunotherapies.