INfluenza Vaccine Indication During anticancer therapy with Immune-checkpoint inhibitors: a transversal challenge for patient’s counselling – preliminary analysis of the retrospective, multicenter, INVIDIa study

Background Split vaccines are allowed during anticancer immunotherapy with immune-checkpoint inhibitors (CKI) and influenza vaccine is recommended in cancer patients. Nevertheless, we hypothesized that patients treated with CKI may have less need for flu vaccine, since immunotherapy enhances cellular and humoral immunity [1]. Moreover, immune-related adverse events of CKI seem to be amplified by flu vaccine, suggesting caution in the patient’s counselling [2]. We planned a retrospective, multicenter study, involving 24 Italian centers, to compare the occurrence of influenza syndrome in advanced cancer patients treated with CKI basing on whether they had received seasonal flu vaccine. Their outcome in terms of overall survival (OS) from CKI starting was also evaluated and then correlated to vaccination and to influenza syndrome among other clinical variables. Methods For this preliminary analysis, consecutive data from advanced cancer patients undergoing treatment with CKI at 14 Italian centers from November 2016 to May 2017 were collected and analyzed. Only patients who started CKI therapy after January 2016 were enrolled. Fisher, Log-rank and Cox regression tests were used for statistical analyses. Results 203 patients were enrolled; the study population characteristics are summarized in Table 1. 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; Figure 1) 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; Figure 4). 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. References 1. Weber JS, Hamid O, Chasalow SD, et al. Ipilimumab increases activated T cells and enhances humoral immunity in patients with advanced melanoma. J Immunother. 2012; 35:89-97. 2. Rothschild S, Balmelli C, Kaufmann L, et al. Immune response and adverse events to influenza vaccine in cancer patients undergoing PD-1 blockade. Abstract ELCC 2017, Geneva, 25 April 2017.