Flu Vaccine in Lung Cancer Patients Could Increase Immunotherapy Toxicities

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Seasonal influenza vaccination resulted in increased risk of immune-related adverse events (AEs) in lung cancer patients treated with PD-1/PD-L1 checkpoint inhibitors in a small study. However, the risks of the flu itself may still outweigh the risks associated with vaccination.

“Use of immune checkpoint inhibitors is now standard clinical practice for many oncology patients, and these same patients-particularly those with lung cancer-also face increased risk for complications from influenza,” said Sacha Rothschild, MD, PhD, of University Hospital Basel in Switzerland, in a press release. “Although routine influenza vaccination has long been recommended for cancer patients, there are concerns that it might trigger an exaggerated immune response in this subgroup receiving checkpoint inhibitors.”

Rothschild presented results of the new study at the European Lung Cancer Conference in Geneva. It included 23 patients, mostly with non–small-cell lung cancer (16 patients), though it also included several with renal cell carcinoma (4 patients) and melanoma (3 patients). All patients except one were receiving nivolumab; the last was receiving pembrolizumab.

The participants received a trivalent influenza vaccination in October or November 2015; a control group of 10 age-matched, healthy partners of patients also received the vaccine.

The vaccine was effective in all patients, with no reported cases of influenza. There was an unusually high frequency of immune-related AEs, however, occurring in 52.2% of patients; six patients (26.1%) had a grade 3 or 4 immune-related AE. The most common such AEs were skin rashes and arthritis (13% each), colitis and encephalitis (8.7% each), and hypothyroidism, pneumonitis, and neuropathy (4.3% each).

“The frequency is significantly higher than the rate of immune-related AEs in unvaccinated patients treated with PD-1/PD-L1 inhibitors,” Rothschild said. At his center, the expected rate of such AEs would be about 25.5%; rates between 30% and 35% have been reported in the literature. “Our hypothesis is that the vaccine results in an overwhelming activation of the immune system in this population.” He added, though, that “there is a particular concern for severe complication of an influenza infection including pneumonia and respiratory failure for patients with lung cancer under immunotherapy.”

Egbert Smit, MD, PhD, of the Netherlands Cancer Institute in Amsterdam, commented on the study, and said that until data from a larger cohort is available, his institution will continue to recommend influenza vaccination regardless of the use of immune checkpoint inhibitors. “This study shows how much we still have to learn about the optimal use of checkpoint inhibitors in lung cancer patients,” he said. “The study is important as it is the first to investigate the impact of influenza vaccination in such patients and there is a hint that we actually put them at increased risk for serious toxicities including encephalitis.”