Flu Shot OK for Cancer Patients on Checkpoint Inhibitors

For cancer patients receiving treatment with immune checkpoint inhibitors for cancer, there was no increase in incidence of immune-related adverse events after receiving the flu shot, researchers found.

No increase in incidence or severity of immune-related adverse events occurred in these advanced stage cancer patients, mostly with lung cancer and melanoma, within 2 months after receiving the inactivated influenza vaccine (IIV), reported Mini Kamboj, MD, of Memorial Sloan-Kettering Cancer Center in New York City, and colleagues.

Importantly, there were no fatal adverse events (such as encephalitis or myocarditis) among this population, and the portion of patients who developed immune-related adverse events was lower than previous reports, the authors wrote in Clinical Infectious Diseases.

They noted that patients with underlying cancer are at higher risk for influenza-related complications, but a recent study from Switzerland found a 52% incidence of immune-related adverse events among vaccinated patients on PD-1 inhibitors, which was characterized as “unexpectedly high.”

“If [the] flu vaccine poses an exaggerated risk of [immune-related adverse events] in patients on [immune checkpoint inhibitors], larger studies are needed to clarify a possible association,” the authors wrote, adding that “many clinicians defer seasonal influenza vaccination” for patients on this therapy, despite the CDC Advisory Committee on Immunization Practices’ (ACIP) recommendations for annual influenza vaccination.

Researchers examined data from patients with advanced cancer at a tertiary care center in New York City who received the influenza vaccine within 65 days of therapy with immune checkpoint inhibitors. These agents included CTLA4 inhibitor ipilimumab (Yervoy), and anti PD-1 agents, pembrolizumab (Keytruda) or nivolumab (Opdivo).

Types of influenza vaccine included standard and high dose, as well as trivalent and quadrivalent, but adjuvanted vaccines were not used. Immune-related adverse events were classified according to the Common Terminology Criteria for Adverse Events five-point grading system. Data were collected for the 2014-2015, 2015-2016, and 2016-2017 influenza seasons.

Overall, 370 patients received a flu shot within 65 days of receiving therapy with immune checkpoint inhibitors. Almost half of examined patients had advanced stage lung cancer, while almost 20% had melanoma. About 60% of patients received therapy with anti PD-1 agents only, while about 20% received combination treatment (ipilimumab plus nivolumab).

There were 75 patients who experienced immune-related adverse events, the most common being grade 3 (36%) and grade 2 (53%). There were no grade 5 adverse events (i.e., those leading to death). The authors found that a little over a quarter of immune-related adverse events were endocrine, 25% were pneumonitis, and colitis or transaminitis were 13% and 12%, respectively. A little under half were managed by steroid or immunosuppressive treatment, while 35% were managed with treatment interruption.

A higher portion of immune-related adverse events occurred among patients treated with ipilimumab plus nivolumab (30%), though the authors noted the incidence was lower than other published reports of 50%-55%. The overall rate of immune-related adverse events for patients on anti PD-1 therapies was 17%, they said.

When comparing this to prior trials, the authors noted the 17% overall rate of immune-related adverse events and the 6.6% rate of grade 3/4 adverse events was “comparable or better than published studies in lung cancer with grade 3/4 IRAE rates typically <20%."

There were only two cases of laboratory-confirmed influenza during the study period, both during the 2016-2017 season, and both influenza A (H3N2), though 36 patients presented with 46 episodes of influenza-like illness >2 weeks after vaccination. This incidence of 3.5% for confirmed influenza among the study cohort was lower than the 10.7% institution-wide incidence, the authors said, and no post-vaccination events or “exaggerated local site reactions” related to influenza vaccine were observed in the study cohort.

Limitations to the data include its retrospective nature, and that the authors were unable to compare risk of immune-related adverse events in vaccinated versus unvaccinated patients, which could introduce both selection bias and “healthy user bias.” Poor clinical documentation may not have captured all immune-related adverse events in the cohort, the authors noted.