CMV serostatus is associated with improved survival and delayed toxicity onset following anti-PD-1 checkpoint blockade

The preprint operates within the dominant paradigm of cancer immunotherapy, specifically focusing on the role of the immune system in mediating responses to checkpoint blockade. It also touches upon the paradigm of viral immunology, particularly concerning the long-term effects of CMV infection on the immune system.

This preprint investigates the impact of CMV serostatus on patient outcomes following anti-PD-1 checkpoint blockade. It presents novel findings within the existing paradigm by demonstrating an association between CMV seropositivity, improved survival in single-agent anti-PD-1 therapy, reduced immune-related adverse events, and potential protection against melanoma development. The research does not challenge the fundamental assumptions of the current cancer immunotherapy paradigm but rather expands our understanding of the complex interplay of factors influencing treatment response. While the interaction with CMV infection and BRAF mutational status hints at potential for future paradigm adjustments in melanoma treatment strategies dependent on these factors, the findings presented primarily contribute to refining existing models within the current paradigm of ICB, hence its classification as Normal Science. There are hints and possibilities for a future Model Drift stage since CMV presence may suggest ICB protocol and dosage adjustments according to BRAF status.