COVID-19 mRNA Vaccination Status and Survival in Patients With Cancer on Immune Checkpoint Inhibitors

Abstract

Certain vaccines may enhance anticancer immune responses, particularly in patients treated with immune checkpoint inhibitors (ICIs), whose efficacy depends on preexisting anticancer immunity. We compared overall survival (OS) in ICI-treated patients with solid tumors according to COVID-19 mRNA vaccination status, timing, and prior dose number. This retrospective cohort study included all adult patients with solid tumors who initiated ICI therapy for the first time in Clalit Health Services hospitals between January 2021 and December 2024. The analysis included 2,888 patients: 145 recently vaccinated (≤30 days before ICI initiation), 2,463 distantly vaccinated (>30 days before ICI initiation), and 280 unvaccinated. Median OS (95% CI) was 24.4 (15.8 to 34.3) months in recently vaccinated patients, 19.8 (17.9 to 21.8) months in distantly vaccinated patients, and 15.5 (13.2 to 18.8) months in unvaccinated patients ( P = .032, log-rank test). Greater number of pre-ICI vaccine doses was also associated with longer observed OS ( P = .043, log-rank test). In multivariable Cox regression analysis adjusting for key clinical covariates, recent vaccination within 30 days before ICI initiation remained significantly associated with improved OS. The association was directionally consistent in additional analyses restricted to vaccinated patients and in inverse probability–weighted analyses. Recent COVID-19 mRNA vaccination before ICI initiation was associated with improved OS in a heterogeneous cohort of patients with solid tumors. These findings are consistent with the hypothesis that recent vaccination-induced immune activation may enhance responsiveness to ICI therapy, although the mechanism cannot be established from this retrospective observational study. Prospective studies are required to determine causality and optimal timing.