Safety of Influenza Vaccine in Patients With Cancer Receiving Pembrolizumab

Jarrett J. Failing, MD; Thanh P. Ho, MD; Siddhartha Yadav, MBBS; Neil Majithia, MD; Irbaz Bin Riaz, MBBS; John Y. Shin, MD; Erin L. Schenk, MD, PhD; Hao Xie, MD, PhD


J Oncol Pract. 2020;16(7):e573-e580. 

In This Article

Abstract and Introduction


Purpose: There is a concern that influenza vaccination could increase the incidence of immune-related adverse events (irAEs) in patients with cancer receiving immune checkpoint inhibitors. The aim of our study was to determine the safety of influenza vaccination in this patient population.

Patients and Methods: We retrospectively identified patients who received at least 1 dose of pembrolizumab during any influenza season from September 2014 to August 2017 and reviewed medical records for irAEs. The primary endpoint was the incidence of irAEs. We used multivariable logistic regression and cumulative incidence curve with competing risks for comparison.

Results: Among 162 patients with cancer included in this study, 70 patients (43.2%) received at least 1 influenza vaccination. The vaccinated group was significantly older (P = .002) and received more cycles of pembrolizumab (P = .006). The incidence of any grade irAEs in the vaccinated group trended toward being lower (25.7% v 40.2%; P = .07) compared with the nonvaccinated group. Influenza vaccination was independently associated with fewer irAEs, with an odds ratio of 0.4 (95% CI, 0.2 to 0.9; P = .03) in multivariable analyses. The vaccinated group was less likely to have irAEs compared with the nonvaccinated group (24.7% v 34.4% at 12 months; P = .05), with death as a competing risk. The median irAE-free duration in the vaccinated group was longer than the nonvaccinated group (not reached v 28 months; P = .037).

Conclusion: Influenza vaccination in patients with cancer receiving immune checkpoint inhibitor therapy was not associated with increased irAEs. This supports the safety of influenza vaccination in this patient population.


Immune checkpoint inhibitors (ICIs) have become a mainstay of cancer immunotherapy in recent years for a number of solid and hematologic malignancies, such as melanoma, lung cancer, renal cell carcinoma, Hodgkin lymphoma, and many others.[1] The most commonly used ICI, pembrolizumab, prevents the tumor-directed downregulation of cancer-specific cytotoxic T cells by blocking the interaction between programmed death receptor-1 (PD-1) and its ligand.[2] For some patients, treatment with an ICI can provide prolonged tumor control, even in previously refractory disease.[3]

However, ICIs can lead to immune-related adverse events (irAEs), presumably due to nonspecific activation of the immune system targeting any healthy tissue and organ.[1] In a series of 88 patients with advanced melanoma treated with pembrolizumab, 12.5% experienced grade 3/4 irAEs. The most common irAEs involved the skin, GI system, and endocrine system, which led to the use of systemic immuno-suppression in 25% of the patients.[4]

Annual influenza vaccinations are recommended by the Center for Disease Control and Prevention (CDC), especially for patients receiving cancer-directed therapies and those who can have increased risk of complications from influenza.[5] A Cochrane review of influenza vaccines in patients with cancer demonstrated lower influenza rates and lower risk of death with vaccination.[6] Specifically, high-dose (compared with standard-dose) influenza vaccine has been shown in meta-analysis to reduce influenza infection risk without serious adverse events in patients over age 65 years.[7] It has previously been shown that for patients who receive ipilimumab (monoclonal antibody against cytotoxic T-lymphocyte–associated antigen 4) and influenza vaccine, most demonstrated an increase in humoral response to influenza B.[8] Several retrospective studies have reported conflicting results on irAE frequency in patients who receive an ICI; however, these studies either had a short follow-up, lack of a comparator, or lack of a reliable way to confirm influenza vaccination status.[9,10] In our study, we retrospectively assessed the prevalence of irAEs in patients with cancer receiving pembrolizumab from our institution who did or did not receive an annual influenza vaccination while receiving ICI therapy.