Flu shot linked to improved survival in melanoma patients receiving immune checkpoint inhibitors

In a study published in February 2026 in JCO Oncology Practice, investigators from Sweden report that influenza vaccination during treatment with immune checkpoint inhibitors was associated with significantly improved progression-free and overall survival. The survival advantage was especially pronounced among patients with cutaneous malignant melanoma, with no increase in immune-related adverse events.

Immune checkpoint inhibitors are a type of immunotherapy that harnesses the patient’s own immune system to fight cancer. Widely used agents such as nivolumab (Opdivo) and pembrolizumab (Keytruda) have reshaped the treatment landscape for advanced cancers, especially melanoma, which is considered one of the most immunogenic tumor types. By unleashing the immune system against cancer cells, these therapies improve outcomes but can also trigger immune-related adverse events.

At the same time, people with cancer are more vulnerable to complications from seasonal influenza, and an annual flu shot is recommended for cancer patients. Still, questions remain about whether stimulating the immune system with a vaccine could alter immunotherapy effectiveness or toxicity.

To explore that issue, a retrospective cohort study was conducted by Antonis Valachis, M.D., Ph.D., associate professor of Oncology at Örebro University in Sweden, and colleagues from Uppsala University Hospital in Sweden. The study included 587 patients with metastatic solid tumors treated with PD-1 or PD-L1 inhibitors, either alone or in combination, between January 2016 and December 2021 across three regions of Sweden. Non-small cell lung cancer and cutaneous malignant melanoma represented the two most common cancer types. About 17% of patients received an influenza vaccine either while on checkpoint inhibitor therapy or within 60 days before starting treatment.

The analysis revealed that, in the overall cohort, influenza vaccination was associated with longer real-world progression-free survival and overall survival, with about a 40% lower risk of disease progression and roughly a 44% lower risk of death from any cause during the study period.

When the investigators looked specifically at tumor types, the survival association appeared strongest in patients with melanoma. In this group, vaccination was linked with approximately a 40% lower risk of disease progression or death and about a 55% lower risk of death overall compared with unvaccinated patients. In contrast, no statistically significant survival difference was observed among patients with non-small cell lung cancer.

Importantly, vaccination was not associated with higher rates of immune-related adverse events. About half of both the vaccinated and unvaccinated groups experienced any-grade toxicities, and the difference was not statistically significant. Rates of severe or multiple immune-related events were also similar between groups.

In their discussion, Valachis and colleagues say the findings add to evidence that influenza vaccination during checkpoint inhibitor therapy may be linked to improved survival, without increasing immune-related adverse events. The association appeared strongest in patients with cutaneous malignant melanoma, although they caution that the subgroup analyses were based on smaller numbers and should be considered exploratory.

“Our study supports the safety of influenza vaccination among patients with cancer treated with checkpoint inhibitors,” Valachis told Managed Healthcare Executive. “With reservation about the study design (retrospective study) and despite the fact that we tried to mitigate main sources of biases, our results trigger the hypothesis that vaccination could potentially serve as an adjunctive therapy when treated with checkpoint inhibitors, although this notion should be officially examined in a prospective manner.”

The authors note that their results align with prior research, including a prospective study of more than 1,100 patients that reported a similar survival trend. They suggest that melanoma’s high tumor mutational burden and inherent immunogenicity could help explain the stronger association, possibly through mechanisms such as cross-reactive T-cell responses. As a retrospective analysis, the study cannot establish causality, but it adds to growing support for influenza vaccination in patients receiving immunotherapy.