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Flu vaccine may cause immune-related adverse events with checkpoint inhibitors
Patients treated with PD-1/PD-L1 checkpoint inhibitors may be at an increased risk for adverse events after receiving the seasonal influenza vaccination, according to prospective study results presented at the European Lung Cancer Conference.
“Use of immune checkpoint inhibitors is now standard clinical practice for many oncology patients, and these same patients — particularly those with lung cancer — also faced increased risk for complications from influenza,” study researcher Sacha Rothschild, MD, PhD, from the division of oncology at University Hospital Basel in Switzerland, said in a press release. “Although routine influenza vaccination has long been recommended for patients with cancer, there are concerns that it might trigger an exaggerated immune response in this subgroup receiving checkpoint inhibitors.”
Rothschild and colleagues evaluated immune responses after vaccination with a trivalent influenza vaccination 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.
No vaccinated patient developed influenza during the season.
However, immune-related adverse events occurred in 52.2% of patients, including six patients (26.1%) who experienced severe grade 3 or grade 4 immune-related adverse events. Historical rates at the researchers’ center are 25.49% for all-grade adverse events and 9.8% for grade 3 or grade 4 adverse events.
“This frequency is significantly higher than the rate of immune-related adverse events in unvaccinated patients treated with PD-1/PD-L1 inhibitors,” Rothschild said. “Our hypothesis is that the vaccine results in an overwhelming activation of the immune system in this population.”
The most common immune-related adverse events included skin rashes (13%), arthritis (13%), colitis (8.7%), encephalitis (8.7%), hypothyroidism (4.3%), pneumonitis (4.3%) and neuropathy (4.3%).
“Although the observed rate of immune-related adverse events in our cohort is alarming, we believe that there is a particular concern for severe complications of an influenza infection — including pneumonia and respiratory failure — for patients with lung cancer under immunotherapy because of concomitant structural lung disorders,” Rothschild said.
The researchers also measured inflammatory chemokines in patients’ peripheral blood to assess a potential induction of a subclinical inflammatory syndrome. However, no significant change appeared between patients and controls shortly after vaccination.
These preliminary results should be tested in a larger study, the researchers noted.
“Some of these patients had prior resection of lung lobes or even a pneumonectomy and, therefore, had limited reserves due to small lung volume,” Rothschild said. “When weighing benefit and potential risk of seasonal influenza vaccination for patients undergoing single-agent PD-1 or PD-L1 blockade — particularly those with lung cancer — we currently advise a case-by-case decision until we have results from larger cohorts.” – by Kristie L. Kahl
Reference:
Rothschild SI, et al. Abstract 112P. Presented at: European Lung Cancer Conference; May 5-8, 2017; Geneva, Switzerland.
Disclosure: The researchers report no relevant financial disclosures.