Flu Vaccine May Cause Immune-Related Adverse Events with Checkpoint Inhibitors

Study results from the division of oncology at University Hospital Basel in Switzerland show that patients treated with PD-1/PD-L1 checkpoint inhibitors may be at an increased risk for adverse events after receiving the seasonal influenza vaccination. In the study, researchers evaluated immune responses after vaccination with a trivalent influenza vaccine in 23 patients (mean age 58.7 years) undergoing checkpoint blockade therapy compared with age-matched controls. Sixteen patients had non-small cell lung cancer, four had renal cell carcinoma and three had melanoma. More than half of patients received at least two prior lines of chemotherapy, and all were receiving PD-1/PD-L1 therapy at the time of vaccination.

All patients developed antibody titers against all three viral strains of influenza, and no patient developed influenza. However, immune-related adverse events occurred in 52.2 percent of patients, including six patients (26.1 percent) who experienced severe grade 3 or grade 4 immune-related adverse events. Historical rates at the researchers’ center are 25.49 percent for all-grade adverse events and 9.8 percent for grade 3 and grade 4 adverse events. The most common immune-related adverse events included skin rashes (13 percent), arthritis (13 percent), colitis (8.7 percent), encephalitis (8.7 percent), hypothyroidism (4.3 percent), pneumonitis (4.3 percent) and neuropathy (4.3 percent). “Our hypothesis is that the vaccine results in an overwhelming activation of the immune system in this population,” said Sacha Rothschild, MD, PhD, at the university.

However, according to Dr. Rothschild, “Although the observed rate of immunerelated adverse events in our cohort is alarming, we believethat thereis a particular concern for severe complications for an influenza infection — including pneumonia and respiratory failure — for patients with lung cancer under immunotherapy because of concomitant structural lung disorders.” The researchers recommended testing these preliminary results in a larger study. “Some of these patients had prior resection of lung lobes or even a pneumonectomy and, therefore, had limited reserves due to small lung volume. When weighing benefit and potential risk of seasonal influenza vaccination for patients undergoing single-agent PD-1 or PD-L1 blocking — particularly those with lung cancer — we currently advise a case-by-case decision until we have results from larger cohorts.”