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;  = 0.035) and PFS (HR = 0.54; 95% CI 0.44-0.66;  < 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).