Dr Olivier Mir of the Gustave Roussy Cancer Institute in Villejuif, France and colleagues from the Curie Institute in Paris, Antony Private Hospital in Antony, Foch Hospital in Suresnes, and Hôtel-Dieu Teaching Hospital in Paris published on 14 March 2020 in the Annals of Oncology results from an observational study conducted during the influenza season 2018/2019. The data suggest that influenza vaccination in patients under immune checkpoint inhibitors is safe and effective. The findings need to be confirmed by larger, prospective studies.
The authors wrote in background that influenza is linked to increased mortality and morbidity in cancer patients compared to the general population. The mortality of influenza infection in cancer patients who are treated with anticancer chemotherapy is around 10%. The efficacy and safety of influenza vaccination in cancer patients who receive chemotherapy has been evaluated in several studies showing an acceptable toxicity profile. However, the rate of seroprotection is reduced compared to immunocompetent patients.
The safety and efficacy of influenza vaccination in cancer patients treated with immune checkpoint inhibitors requires further investigation. In the largest study addressing that issue, the investigators from France included 30 patients of whom 25 with non-small cell lung cancer and 5 with urothelial cancer. Majority of patients were males (83%) with median age 63 years (range: 47-78). Seven patients received single agent nivolumab, 8 patients received pembrolizumab and 15 patients received atezolizumab. The median time under treatment with immune checkpoint inhibitors at the time of vaccination was 3 months (range: 1-28).
Patients received a single, standard dose of subcutaneous influenza vaccine approved by French National Health authorities 7 days (+/-2) after the last administration of therapy with immune checkpoint inhibitors. Influenza A (H1N1 and H3N2) antibody titers were measured at baseline and at days 21 and 42 after vaccination, according to assay approved by World Health Organization.
At day 42 post-vaccination, the study team observed seroprotective rates of 71%, 63% and 67% against H1N1, and 57%, 63% and 67% against H3N2 in patients receiving nivolumab, pembrolizumab and atezolizumab, respectively. Seroconversion factors were high, with 7 patients (23%) showing a seroconversion factor > 1000. Influenza infection was not documented among the 30 vaccinated patients during the 6 months following vaccination.
With regard to toxicity, no grade 4-5 immune-related adverse event (irAE) was observed, and 15 patients (50%) developed grade 1-3 irAEs during the 6 months following the influenza vaccination.
The authors emphasised in their article that in order to tackle the major public health matter of influenza-related mortality in cancer patients, efforts are needed to improve vaccination rates not only among cancer patients and their relatives, but also among the healthcare providers. Vaccination rate in healthcare providers remains inadequate, particularly among medical trainees and nurses who often refuse vaccination for erroneous reasons, including not considering them as vectors or fear of side effects.
Bayle A, Khettab M, Lucibello F, et al. Immunogenicity and safety of influenza vaccination in cancer patients receiving checkpoint inhibitors targeting PD-1 or PD-L1. Annals of Oncology; Published online 14 March 2020. DOI: https://doi.org/10.1016/j.annonc.2020.03.290