Concomitant use of H1 antihistamines improves survival outcomes in cancer patients on immune checkpoint inhibitor therapy: a systematic review and meta-analysis

Introduction The rapid progress of immuno-oncology has transformed cancer pharmacotherapy through immune checkpoint inhibitors (ICIs); however, only a minority of patients experience durable benefits. Recent evidence suggests that concomitant administration of H1 antihistamines may synergistically enhance ICI efficacy by modulating the tumor immune microenvironment. This meta-analysis evaluated the association between H1 antihistamine use and outcomes in cancer patients undergoing ICI therapy.Methods Comprehensive searches were conducted in PubMed, Embase, and Web of Science to identify studies comparing overall survival (OS) and progression-free survival (PFS) between ICI users with and without H1 antihistamines. Pooled hazard ratios (HRs) were calculated using a random-effects model (REML) in R software (v4.4.2).Results Six retrospective cohort studies encompassing 2166 patients (417 antihistamine users and 1749 non-users) were included, primarily involving lung cancer (34.5%) and melanoma (13%). H1 antihistamine use was significantly associated with improved OS (HR = 0.64; 95% CI 0.42–0.97; p = 0.035) and PFS (HR = 0.54; 95% CI 0.44–0.66; p < 0.001).Conclusions These findings indicate that H1 receptor blockade may potentiate the therapeutic efficacy of ICIs, resulting in better survival and delayed disease progression. The integration of antihistamines with ICIs may represent a promising and cost-effective adjunct strategy in cancer immunotherapy.Registration PROSPERO (CRD420251207396).