Influenza vaccine indication during anticancer therapy with immune-checkpoint inhibitors: A transversal challenge for patient’s counselling – preliminary analysis of the INVIDIa study

Background: Split vaccines are allowed during treatment with immune-checkpoint inhibitors (CKI) and flu vaccine is recommended in cancer patients, despite it seem to amplify immune-related adverse events of CKI and it may be not necessary, since immunotherapy enhances cellular and humoral immunity. We planned a retrospective study at 24 Italian centers, to compare the occurrence of flu syndrome in advanced cancer patients treated with CKI receiving or not flu vaccine. Overall survival (OS) was also evaluated. Methods: For this preliminary analysis, consecutive data from patients undergoing treatment with CKI at 14 Italian centers from November 2016 to May 2017 were analyzed. Only patients who started CKI after 1th of January 2016 were enrolled. Results: 203 patients (I-VII treatment line; 77 renal carcinoma, 73 lung cancer, 40 melanoma, 13 others) were enrolled. Median OS was not reached at the median follow-up of 10.2 months (172 censored). 50 patients received flu vaccine. Median time from CKI starting to vaccine was 2 months (mean 3 months). Overall, 29 patients developed flu syndrome: its incidence among vaccinated patients was 30% vs 9.2% of unvaccinated (OR 3.28 95%CI 1.70-6.33, p 0.001). Median time from vaccine to flu syndrome was 2 months (mean 3 months). At 18 months, OS of vaccine group was 83% vs 63% of unvaccinated (p 0.134). Patients who developed flu syndrome had a non-statistically significant trend for better OS compared with unaffected patients (92% vs 63% at 18 months, p 0.127). The 64 patients who had vaccine and/or influenza had significantly better OS (OR 0.52, p 0.049) compared with those not vaccinated nor infected (85% vs 59% at 18 months). At multivariate analysis only treatment response was significantly related to OS (OR 7.3, 95%CI 3.9-13.5, p < 0.001). Conclusions: With the limit of retrospective study and immature data, it seems that the incidence of influenza among advanced cancer patients treated with CKI is boosted by flu vaccine. Nevertheless, to receive flu vaccine or to develop flu syndrome may prolong survival. Flu vaccine seems to be ineffective in these patients, but it might have positive effect on outcome.