Influenza Vaccination Among Patients With Cancer Treated With Checkpoint Inhibitors: Association With Survival Outcomes and Immune-Related Adverse Events.

Abstract

Purpose: Patients with cancer receiving immune checkpoint inhibitors (CPIs) may experience immune-related adverse events (IRAEs) due to immune system overactivation. Concurrently, infections such as seasonal influenza can be more severe in cancer patients because of their compromised immune function, making influenza vaccination particularly important. In this multicenter retrospective study, we investigated whether influenza vaccination during CPI treatment influences CPI effectiveness and rates of IRAEs.

Patients and methods: We conducted a retrospective cohort study across three Swedish centers involving patients with metastatic cancer treated with CPIs-either PD-1/PD-L1 inhibitors or combination immunotherapy-between January 1, 2016, and December 31, 2021. To address immortal time bias in time-to-event outcomes, different statistical strategies were employed including time-dependent Cox regression and landmark analyses.

Results: In total, 587 patients treated with CPIs during the study period were identified. The most common malignancy was non-small cell lung cancer (NSCLC; 34.4%), followed by cutaneous malignant melanoma (CMM; 32.5%). Time-dependent Cox regression analysis showed that real-world progression-free survival was significantly longer in influenza-vaccinated patients compared with unvaccinated in overall cohort (hazard ratio [HR], 0.59 [95% CI, 0.44 to 0.79]). No statistically significant differences in the occurrence of any grade IRAEs (48.4% v 51.2%, P = .455) or multiple IRAEs (15.1% v 19.2%, P = .297) between the vaccinated and unvaccinated groups were observed. The survival benefit was more pronounced in patients with CMM, whereas no statistically significant effect was observed in patients with NSCLC.

Conclusion: Our findings suggest a potential association between influenza vaccination and improved survival in CPI-treated patients, without a corresponding increase in IRAEs, supporting current vaccination recommendations. The observed association in patients with CMM may reflect underlying biological mechanisms and is hypothesis-generating for further investigation.