Evidence date · 2022-06-01 · Research note 2 of 3
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Since the previous research note · Partly supported
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Since the previous research note: Can a vaccine prompt antibodies during checkpoint cancer treatment?
Previous expectation: Larger prospective studies might connect vaccine antibody responses to protection and clarify immune side effects during checkpoint treatment.
What this study adds: This review pooled immune-side-effect outcomes from six studies involving 1,285 patients and death outcomes from three studies involving 589; neither comparison was statistically significant, and most underlying data remained retrospective.
What changed in this study
Checkpoint inhibitors are a form of cancer immunotherapy. For people receiving them, a practical question is whether a flu shot could add immune-related side effects. A 2022 systematic review and meta-analysis found no statistically significant difference between vaccinated and unvaccinated patients in either death or immune-related adverse events. That is a useful result to examine, but it does not show that the risks are identical or that vaccination carries no risk.
A broad search produced a narrower evidence base
The authors searched PubMed and EMBASE through October 26, 2021. They considered peer-reviewed studies and conference abstracts involving people treated with immune checkpoint inhibitors who had received at least one dose of influenza vaccine. In all, 25 studies entered the systematic review, and nine were included in the meta-analysis.
The pooled estimates drew on smaller, outcome-specific groups. Three studies with 589 patients contributed to the comparison of death. Six studies with 1,285 patients contributed to the comparison of any immune-related adverse event, often shortened to irAE. These are side effects associated with immune activity during treatment. So the nine-study count does not describe the evidence behind either outcome on its own: each estimate came from a subset of studies.
The two estimates point in different directions
An odds ratio compares the odds of an outcome in two groups. An odds ratio of 1 indicates no difference; a value above 1 points to higher odds in the vaccinated group, and a value below 1 points to lower odds.
For death, the pooled odds ratio was 1.25, with a 95% confidence interval from 0.81 to 1.92. The estimate is above 1, but its interval includes 1 and extends both below and above it. The comparison therefore did not establish higher or lower odds of death among vaccinated patients.
For any irAE, the pooled odds ratio was 0.82, with a 95% confidence interval from 0.63 to 1.08. This estimate is below 1, but its interval also crosses 1. Here, too, the pooled result did not establish an increase or a decrease. Because both intervals include the no-difference value, these results are not proof that vaccinated and unvaccinated patients had equal risks; the data remain compatible with differences in either direction.
Side effects and influenza protection are different questions
The review’s safety comparisons focused on death and immune-related side effects. They do not show how well influenza vaccination prevented infection or illness in people receiving checkpoint inhibitors. A death comparison is not a direct measure of protection from influenza, and the reported findings cannot quantify that protection in this patient group.
Most of the underlying evidence came from retrospective observational studies. Researchers looked back at existing patient data rather than assigning vaccination at random. As a result, other differences between vaccinated and unvaccinated patients could affect the outcomes, and these comparisons cannot establish that vaccination caused a change in death or irAEs.
The authors describe similar findings in sensitivity analyses for serious irAEs and for peer-reviewed studies alone. They also call for randomized studies. Those checks offer context about the reported pattern, while the observational design still limits what can be concluded about cause and effect.
How clearer evidence could guide flu shots during checkpoint therapy
If prospective studies confirm an acceptable safety profile and establish meaningful protection against influenza during checkpoint treatment, patients and cancer teams could make vaccination decisions with firmer knowledge of both potential immune side effects and likely benefit. That would make it possible to weigh these questions using evidence from the treated population itself.
Key Sources
- Primary source: Influenza Vaccination in Cancer Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis.
DOI or Journal Page · Review or Meta-Analysis · 2022-06-01