Cancer Type and Histology Influence Cutaneous Immunotherapy Toxicities: A Multi-Institutional Cohort Study.

in The British journal of dermatology by Guihong Wan, Sara Khattab, Bonnie W Leung, Shijia Zhang, Nga Nguyen, Matthew Tran, Chuck Lin, Crystal Chang, Nora Alexander, Ruple Jairath, Jordan Phillipps, Kimberly Tang, Ahmad Rajeh, Leyre Zubiri, Steven T Chen, Shadmehr Demehri, Kun-Hsing Yu, Alexander Gusev, Shawn G Kwatra, Nicole R LeBoeuf, Kerry L Reynolds, Yevgeniy R Semenov

TLDR

  • This study looked at how different types of cancer and their histology (the way the cells look under a microscope) affect the development of cutaneous immune-related adverse events (cirAEs) in people who are getting immune checkpoint inhibitor (ICI) therapy. The study found that people with certain types of cancer, like cutaneous squamous cell carcinoma (cSCC), melanoma, head and neck adenocarcinoma, genitourinary transitional cell carcinoma, and genitourinary adenocarcinoma, were at a higher risk of developing cirAEs. The study also found that people with these types of cancer who developed cirAEs had a better survival outcome. The study highlights the importance of identifying patients who are at increased risk of developing cirAEs and developing personalized treatment strategies for patients with cutaneous malignancies treated with ICIs.

Abstract

Cutaneous immune-related adverse events (cirAEs) are the most common toxicities to occur in the setting of immune checkpoint inhibitor (ICI) therapy. Identifying patients who are at increased risk of developing cirAEs may improve quality of life and outcomes. To investigate the influence of cancer type and histology on the development of cirAEs in the setting of ICI therapy and survival outcomes. This retrospective cohort study included patients between December 1, 2011, and October 30, 2020. They received ICIs from 2011-2020 with follow-up of outcomes through October 2021. We identified 3,668 ICI recipients who were seen at Mass General Brigham and Dana-Farber. Of these, 669 developed cirAEs. Records that were incomplete or categories of insufficient sample size were excluded from the study cohort. Multivariate Cox proportional hazards models were utilized to investigate the impact of cancer organ system and histology on cirAE development, after adjusting for demographics, Charlson Comorbidity Index, ICI type, cancer stage at ICI initiation, and year of ICI initiation. Time-varying Cox proportional hazards modeling was utilized to examine the impact of cirAE development on mortality. Compared to other non-epithelial cancers (neuroendocrine, leukemia, lymphoma, myeloma, sarcoma, and central nervous system malignancies), cutaneous squamous cell carcinoma (cSCC) (HR = 3.57, p < 0.001), melanoma (HR = 2.09, p < 0.001), head and neck adenocarcinoma (HR = 2.13, p = 0.009), genitourinary transitional cell carcinoma (HR = 2.15, p < 0.001), and genitourinary adenocarcinoma (HR = 1.53, p = 0.037) were at significantly higher risk of cirAEs in multivariate analyses. The increased risk of cirAEs translated into an adjusted survival benefit for melanoma (HR = 0.37, p < 0.001) and cSCC (HR = 0.51, p = 0.011). The highest rate of cirAEs and subsequent survival benefits were observed in cutaneous malignancies treated with ICIs. This study improves our understanding of patients who are at highest risk of developing cirAEs and would, therefore, benefit from appropriate counseling and closer monitoring by their oncologists and dermatologists throughout their ICI therapy. Limitations include its retrospective nature and cohort from one geography.

Overview

  • The study investigates the influence of cancer type and histology on the development of cutaneous immune-related adverse events (cirAEs) in the setting of immune checkpoint inhibitor (ICI) therapy and survival outcomes. The study included patients between December 1, 2011, and October 30, 2020, who received ICIs from 2011-2020 with follow-up of outcomes through October 2021. The study identified 3,668 ICI recipients who were seen at Mass General Brigham and Dana-Farber. Of these, 669 developed cirAEs. Records that were incomplete or categories of insufficient sample size were excluded from the study cohort. Multivariate Cox proportional hazards models were utilized to investigate the impact of cancer organ system and histology on cirAE development, after adjusting for demographics, Charlson Comorbidity Index, ICI type, cancer stage at ICI initiation, and year of ICI initiation. Time-varying Cox proportional hazards modeling was utilized to examine the impact of cirAE development on mortality. The study aims to answer the question of how cancer type and histology influence the development of cirAEs in the setting of ICI therapy and survival outcomes.

Comparative Analysis & Findings

  • The study found that cutaneous squamous cell carcinoma (cSCC), melanoma, head and neck adenocarcinoma, genitourinary transitional cell carcinoma, and genitourinary adenocarcinoma were at significantly higher risk of cirAEs in multivariate analyses. The increased risk of cirAEs translated into an adjusted survival benefit for melanoma and cSCC. The highest rate of cirAEs and subsequent survival benefits were observed in cutaneous malignancies treated with ICIs. The study found that cancer type and histology significantly influence the development of cirAEs in the setting of ICI therapy and survival outcomes.

Implications and Future Directions

  • The study's findings highlight the importance of identifying patients who are at increased risk of developing cirAEs, which may improve quality of life and outcomes. The study suggests that cutaneous malignancies treated with ICIs are at the highest risk of cirAEs and subsequent survival benefits. Future research should focus on developing personalized treatment strategies for patients with cutaneous malignancies treated with ICIs, as well as exploring the role of other factors, such as age and comorbidities, in the development of cirAEs. Additionally, further studies are needed to validate the findings of this study in other geographic regions and populations.
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