Clinical outcomes in patients with metastatic non-small cell lung cancer and head and neck squamous cell cancer treated with immune checkpoint inhibitors according to COVID-19 vaccination status.
Authors: Khaddour Karam , Kamel Josette Mary , Meeder Natalie , Ziqiao Xu , Sandra Cuellar , Pasquinelli Mary , Nguyen Ryan Huu-Tuan , Liu Li C. , Gadi Vijayakrishna K. , Feldman Lawrence Eric , Weinberg Frank 
Published: June 2023

e14696 Background: Immune checkpoint inhibitor (ICI) constitute the mainstay of therapy in metastatic non-small cell lung cancer (NSCLC) and head and neck squamous cell cancer (HNSCC). Infectious vaccines administered intratumorally or systemically have been suggested to enhance response to ICI and improve outcomes. No data is available on the effect of COVID-19 vaccines on clinical outcomes in patients treated with ICI. The aim of the study is to investigate overall survival (OS), progression-free survival (PFS), and immune related adverse events (IRAEs) according to mRNA COVID-19 vaccination status in patients with metastatic NSCLC and HNSCC who were treated with ICI. Methods: We performed retrospective analysis of clinical outcomes between a cohort of patients treated with ICI who received at least one dose of COVID-19 vaccine, and a historic control group of patients who did not receive COVID-19 vaccine and did not have documented COVID-19 infection. We included patients with metastatic NSCLC and HNSCC who had received at least one dose of ICI, either as monotherapy or in combination with chemotherapy or targeted therapy. Patients were stratified by age, gender, ethnicity, COVID-19 vaccination status, number of vaccinations, treatment type (monotherapy versus combined), treatment line, and PD-L1 status. Endpoints included IRAEs, PFS and OS. Results: A total of 151 patients met inclusion criteria (94 vaccinated and 57 control). Mean age at diagnosis was 62 years, the majority were female (51%), African American (58.3%), and received ICI monotherapy (57.6%). There was prolonged OS in patients who received COVID-19 vaccination versus control group ( p-value=0.04). In a multivariate analysis, patients in the COVID-19 vaccine arm had significantly reduced hazard of dying (HR:0.49, p =0.0446) when controlled for all of the above variables, and each additional received vaccine was associated with significant reduced hazard (HR=0.701, p-value = 0.0099). Race and type of cancer were statistically associated with PFS. Controlled for these factors, COVID arm patients had reduced hazard of disease progression (HR = 0.58, p-value = 0.0506), and each additional received mRNA vaccine was associated with a significantly reduced hazard of progression (HR = 0.74, p-value = 0.0046). There was no significant difference in the rate of IRAEs between vaccinated and non-vaccinated patients ( p=0.71). Conclusions: In this sample of patients with metastatic NSCLC and HNSCC who received ICI, there was significant improvement in OS between patients who received a COVID-19 vaccine compared patients who did not receive vaccination and did not have COVID-19 infection. There were no significant differences in IRAEs. Further studies are required to assess whether there is a synergistic effect between COVID-19 vaccination and ICI efficacy.