Immune response and adverse events to influenza vaccine in cancer patients undergoing PD-1 blockade

Abstract

Background: Cancer patients (pts) are at risk to develop complications when infected with seasonal influenza viruses. Current guidelines propose that pts on PD-1 directed therapies may receive concurrent inactivated influenza immunization if not medically contraindicated. In this observational study, we aimed to assess the vaccine induced immune response and safety of immunotherapy and influenza vaccine. Methods: Metastatic cancer pts treated with at least one dose of either nivolumab or pembrolizumab were vaccinated with a trivalent inactive influenza vaccination between October and November 2015. Partners of the pts were vaccinated and included in our analysis as agematched controls. Antibody titers against vaccine virus strains were measured by hemagglutination inhibition assay at days 7, 30, 60 and 180. Cytokine/chemokine profile and changes in peripheral immune cells were assessed in cancer pts at the same time points. Immunerelated adverse events (irAE) were documented according to CTCAE v4.0. Results: We included 23 pts and 7 age-matched healthy controls. Median time between initiation of PD-1 inhibition and influenza vaccination was 74 days (range, 44-57). 22 pts were treated with nivolumab and 1 pt with pembrolizumab. 16 pts had a diagnosis of non-small cell lung cancer, 3 pts had renal cell carcinoma and 3 pts a malignant melanoma. In total, 12 pts (52.2%) experienced an irAE. 6 pts (26.1%) had grade 3 or 4 (G3/4) irAEs. This frequency seems to be higher than reported in the literature. G3/4 irAEs include colitis (n = 2), encephalitis (n = 1), vasculitis (n = 1), pneumonitis (n = 1), peripheral neuritis (n = 1). There was no major difference over time in the generation of antibody titers against strains in the vaccine. Peripheral leukocyte counts and cytokine/inflammatory chemokine levels were unchanged after vaccination. We did not observe unexpected local toxicities at the injection site. Conclusions: The seasonal influence vaccination reaches a protective range in these pts. Unexpectedly, however, an increased rate of clinically relevant irAEs was observed. Confirmation in a larger population and mechanistic understanding is required.