Deconvolving SARS-CoV-2 mRNA vaccine impact on immunotherapy-related survival in a pandemic

Real-world data suggest that SARS-CoV-2 mRNA vaccines, administered within 100 days of immune checkpoint inhibitor (ICI) treatment ("peri-ICI vaccination"), may improve ICI effectiveness, potentially through synergistic immune priming. Although peri-ICI vaccination was associated with longer survival when we applied a previous framework to our independent dataset, additional patterns emerged. Peri-ICI vaccination benefit diminished after 2021, a pattern confirmed in re-analysis of a published cohort. Benefit extended to patients treated with non-ICI antineoplastics. Benefit also dissipated in landmarked analyses restricted to periods of vaccine eligibility. Finally, progression-free survival in time periods with high vaccine uptake was not longer than in periods without vaccination. These analyses suggest peri-ICI vaccination's observed association with survival largely reflects selection bias in which patients with better prognosis were more likely to receive SARS-CoV-2 vaccines.