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Re-evaluating the effect of SARS-CoV-2 mRNA vaccination on clinical outcomes in patients treated with immune checkpoint inhibitors

Dumas, E.; Gougis, P.; Gasparollo, L.; Spano, J.-P.; Stensrud, M. J.

2025-11-04 oncology
10.1101/2025.11.03.25339367 medRxiv
Show abstract

SARS-CoV-2 mRNA vaccination (COVID-19 vaccination) within 100 days of immune checkpoint inhibitor (ICI) treatment was reported to improve survival and prevent disease progression in patients with non-small cell lung cancer (NSCLC) and metastatic melanoma (Grippin et al., Nature, 2025). However, the clinical evidence, derived from real-world observational data, might suffer from methodological limitations, including immortal-time bias. These key limitations can be overcome by carefully designing a target trial emulation analysis. Using the data made publicly available by the authors, we emulated a target trial that would identify the causal effect of COVID-19 vaccination within 100 days of first ICI on overall survival and progression-free survival in patients with NSCLC and metastatic melanoma. In contrast to the original analysis, we found no evidence that COVID-19 vaccination improves survival outcomes in these populations. The original results likely reflect biases inherent to non-causal observational analyses. To clarify the true effect of COVID-19 vaccination in this setting, larger and suitably designed studies are needed.

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