Abstract
PURPOSE: Recent research (Li et al. 2021) suggests an upregulated expression and activation of H1 receptors on macrophages in the tumor microenvironment, and concomitant H1-antihistamine use is associated with improved overall survival in patients with lung and skin cancers receiving immunotherapy. Therefore, we retrospectively evaluated the impacts of H1-antihistamine use in cancer patients during immunotherapy. METHODS: All patients who had received at least one dose of immune checkpoint inhibitors (ICIs) from July 1, 2014 to October 31, 2019 were identified from Hong Kong's territory-wide database, with this date defined as the baseline. A 1-month landmark analysis was conducted with follow-for up to 6 months, including an exposure period of 1 month before and after the baseline date. Patients were grouped according to the types of primary cancer and the percentages of daily H1-antihistamine usage within the exposure period. The primary outcome was overall survival. RESULTS: A total of 1740 (65.1% male, mean age 61.9 years) were included in the landmark analysis, of which 529 (30.4%) and 307 (17.6%) had primary lung and liver malignancies. The multivariable Cox regression model estimated statistically significant improvement in overall survival of intermediate use in patients with primary lung malignancies (adjusted hazard ratio [aHR] 0.223, 95% confidence interval [CI] 0.052-0.958, p = 0.044), but not with primary liver maligancies. Similar frequency-dependent effects were identified in Kaplan-Meier analysis. CONCLUSION: The benefits of adjunctive use of H1-antihistamines may be generation- and tumor-dependent. Further clinical and mechanistic studies are required to confirm the findings.