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- Title
Incidence of Cutaneous Immune-Related Adverse Events and Outcomes in Immune Checkpoint Inhibitor-Containing Regimens: A Systematic Review and Meta-Analysis.
- Authors
Curkovic, Nina B.; Bai, Kun; Ye, Fei; Johnson, Douglas B.
- Abstract
Simple Summary: Immune checkpoint inhibitors are increasingly being used in the treatment of a variety of cancers, both alone and in combination with other cancer therapies. Side effects often include skin reactions, which may occur more frequently in therapeutic regimens consisting of multiple immune checkpoint inhibitors. We conducted a systematic review and meta-analysis of clinical trials to better understand the frequency of skin reactions secondary to immune checkpoint inhibitors, known as cutaneous immune-related adverse events, across several different immune checkpoint inhibitor regimens, doses, and cancers. Our analysis provides benchmark incidence rates for cutaneous immune-related adverse events including pruritis, rash, and vitiligo, and validates previously reported links between the development of cutaneous immune-related adverse events and outcomes of therapy. Immune checkpoint inhibitors (ICIs) are used to treat many cancers, and cutaneous immune-related adverse events (cirAEs) are among the most frequently encountered toxic effects. Understanding the incidence and prognostic associations of cirAEs is of importance as their uses in different settings, combinations, and tumor types expand. To evaluate the incidence of cirAEs and their association with outcome measures across a variety of ICI regimens and cancers, we performed a systematic review and meta-analysis of published trials of anti–programmed death-1/ligand-1 (PD-1/PD-L1) and anti–cytotoxic T lymphocyte antigen-4 (CTLA-4) ICIs, both alone and in combination with chemotherapy, antiangiogenic agents, or other ICIs in patients with melanoma, renal cell carcinoma, non-small cell lung cancer, and urothelial carcinoma. Key findings of our study include variable cirAE incidence among tumors and ICI regimens, positive association with increased cirAE incidence and response rate, as well as significant association between increased vitiligo incidence and overall survival. Across 174 studies, rash, pruritis, and vitiligo were the most reported cirAEs, with incidences of 16.7%, 18.0%, and 6.6%, respectively. Higher incidence of cirAEs was associated with ICI combination regimens and with CTLA-4-containing regimens, particularly with higher doses of ipilimumab, as compared to PD-1/L1 monotherapies. Outcome measures including response rate and progression-free survival were positively correlated with incidence of cirAEs. The response rate and incidence of pruritis, vitiligo, and rash were associated with expected rises in incidence of 0.17% (p = 0.0238), 0.40% (p = 0.0010), and 0.18% (p = 0.0413), respectively. Overall survival was positively correlated with the incidence of pruritis, vitiligo, and rash; this association was significant for vitiligo (p = 0.0483). Our analysis provides benchmark incidence rates for cirAEs and links cirAEs with favorable treatment outcomes at a study level across diverse solid tumors and multiple ICI regimens.
- Subjects
PROGRAMMED cell death 1 receptors; IMMUNE checkpoint inhibitors; META-analysis; PROGRAMMED death-ligand 1; SYSTEMATIC reviews; HEALTH outcome assessment; EXANTHEMA; IPILIMUMAB; ITCHING; RESEARCH funding; DRUG eruptions; DRUG side effects; VITILIGO
- Publication
Cancers, 2024, Vol 16, Issue 2, p340
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers16020340