Abstract: We identified six studies with a total of 2275 participants: five studies comparing vaccination with no vaccination, and one comparing adjuvanted vaccine with non-adjuvanted vaccine. Three studies were RCTs, one was a prospective observational cohort study and two were retrospective cohort studies. For the comparison of vaccination with no vaccination we included two RCTs and three observational studies, including 2202 participants. One study reported results in person-years while the others reported results per person. The five studies were performed between 1993 and 2015 and included adults with haematological diseases (three studies), patients following bone marrow transplantation (BMT) (two studies) and solid malignancies (three studies). One RCT and two observational studies reported all-cause mortality; the RCT showed similar mortality rates in both arms (odds ratio (OR) 1.25 (95% CI 0.43 to 3.62; 1 study, 78 participants, low-certainty evidence)); and the observational studies demonstrated a significant association between vaccine receipt and lower risk of death, adjusted hazard ratio 0.88 (95% CI 0.78 to 1; 1 study, 1577 participants, very low-certainty evidence) in one study and OR 0.42 (95% CI 0.24 to 0.75; 1 study, 806 participants, very low-certainty evidence) in the other. One RCT reported a reduction in ILI with vaccination, while no difference was observed in one observational study. Confirmed influenza rates were lower with vaccination in one RCT and the three observational studies, the difference reaching statistical significance in one. Pneumonia was observed significantly less frequently with vaccination in one observational study, but no difference was detected in another or in the RCT. One RCT showed a reduction in hospitalisations following vaccination, while an observational study found no difference. No life-threatening or persistent adverse effects from vaccination were reported. The strength of evidence was limited by the low number of included studies and by their low methodological quality and the certainty of the evidence for the mortality outcome according to GRADE was low to very low. For the comparison of adjuvanted vaccine with non-adjuvanted vaccine, we identified one RCT, including 73 patients. No differences were found for the primary and all secondary outcomes assessed. Mortality risk ratio was 0.54 (95% CI 0.05 to 5.73; low-certainty evidence) in the adjuvanted vaccine group. The quality of evidence was low due to the small sample size and the large confidence intervals for all outcomes. Observational data suggest lower mortality and infection-related outcomes with influenza vaccination. The strength of evidence is limited by the small number of studies and low grade of evidence. It seems that the evidence, although weak, shows that the benefits overweigh the potential risks when vaccinating adults with cancer against influenza. However, additional placebo or no-treatment controlled RCTs of influenza vaccination among adults with cancer is ethically questionable.There is no conclusive evidence regarding the use of adjuvanted versus non-adjuvanted influenza vaccine in this population.

Plain-language summary: We identified six clinical studies (2275 participants) addressing this question, half of which were randomised controlled trials, where patients were randomly selected to get or not to get the vaccine. Two other studies showed that adults with cancer who were vaccinated were found to have lower rates of death, but these studies were not randomised. One small randomised study showed a similar mortality rate in vaccinated and non-vaccinated patients. Pooling (combining) results from the different studies was not possible because of different methods or different ways the results were reported. There was a lower rate of influenza-like illness (any febrile respiratory illness), pneumonia, confirmed influenza and hospitalisation for any reason, among vaccinated people in at least one study. No side effects to the vaccine were reported in these studies. The review also included a trial comparing the regular vaccine to a vaccine containing an adjuvant that is supposed to increase the immune response. This randomised trial was small and did not find differences in all clinical outcomes examined. The strength of evidence is limited by the low number of studies and by their low methodological quality (high risk of bias). It is unlikely that there will be any future large-scale controlled trials to investigate this issue. The current evidence, although weak, suggests a benefit for influenza vaccination amongst adults with cancer and the vaccine was not found to be harmful. Influenza vaccines given to adults with cancer contain an inactivated virus that cannot cause influenza or other viral infection.