key: cord-0821131-wp1u2b92
authors: Chen, Yu-Wei; Tucker, Matthew D.; Beckermann, Kathryn E.; Iams, Wade T.; Rini, Brian I.; Johnson, Douglas B.
title: COVID-19 mRNA Vaccines and Immune-Related Adverse Events in Cancer Patients Treated with Immune Checkpoint Inhibitors
date: 2021-07-28
journal: Eur J Cancer
DOI: 10.1016/j.ejca.2021.07.017
sha: bcbc031df00f780217441cfe79bac85d292480d3
doc_id: 821131
cord_uid: wp1u2b92

nan

The Coronavirus Disease 2019 (COVID-19) messenger RNA (mRNA) vaccines, BNT162b2 and mRNA-1273, manufactured by Pfizer-BioNTech and Moderna, respectively, received the United States Food and Drug Administration (FDA) emergency use authorization in December 2020 and have since been widely administered. Recognizing the increased mortality risk from COVID-19 in cancer patients 1 , the major cancer scientific societies such as the American Society of Clinical Oncology (ASCO) 2 , European Society for Medical Oncology (ESMO) 3 , and National Comprehensive Cancer Network (NCCN) 4 generally recommend COVID-19 vaccination in cancer patients if there are no contraindications. However, patients with active cancer were excluded from the landmark vaccine trials 5 . In addition, immune checkpoint inhibitors (ICIs) now constitute the contemporary standard-of care systemic regimens across various cancer types. Therefore, there is a concern regarding the risk of immune-related adverse events (irAEs) after administration of COVID-19 mRNA vaccines in patients with cancer treated with an ICI, albeit there is paucity of data.

To further investigate this essential topic in cancer care, we conducted a retrospective chart review using the electronic medical record at Vanderbilt University Medical Center (VUMC). The study cohort included cancer patients who received ICIs within one month of receiving a COVID-19 mRNA vaccine. All patients received two doses of COVID-19 mRNA vaccine as recommended by the manufacturers and had at least 30 days of follow-up after the second dose of vaccine. The primary outcome was the rate of irAEs. Additionally, the United States Centers of Disease Control (CDC) and FDA's Vaccine Adverse Event Reporting System (VAERS) database was reviewed for reported possible irAEs after COVID-19 vaccine administration. This study was approved by the institutional review board at VUMC.

There were 81 patients at VUMC who met criteria for analysis ( Table 1 ). The median age was 70 and 60% were male. The most common cancer subtype was lung (27%), followed by melanoma (23%), kidney cancer (14%), and gastrointestinal/hepatic cancer (11%). Most patients received pembrolizumab (56%) or nivolumab (27%). The median duration of ICI treatment prior to vaccination was 6.6 months [interquartile range (IQR): 2.1-11.2]. The median duration between the most recent ICI infusion and the second dose of COVID-19 vaccine was 13 days (IQR: 8-20). 9 patients (11%) had irAEs prior to COVID-19 vaccination (all ≤ grade 2). Patients received either the Pfizer-BioNTech (83%) or Moderna (17%) COVID-19 vaccine. After a minimum of 30 days of follow-up from the second dose of vaccine, zero of the 84 (95% CI, 0.0%-4.5%) patients had exacerbation of previous irAEs or diagnosis of new irAEs. One patient died during the 30-day follow-up due to cancer progression.

As of the data cut-off date, May 14, 2021, there were 152,748 adverse events following the administration of COVID-19 mRNA vaccines reported to the VAERS. There were 24 events reported in patients concurrently receiving ICIs, and six of them had clinical presentations suspicious for irAEs (Table 2) , including two with possible flares of pre-existing irAEs and four de novo irAEs.

We observed no signal of increased risk of development or exacerbation of irAEs after mRNA COVID-19 vaccination (either the Pfizer-BioNTech or Moderna vaccine) among cancer patients who were on active treatment with ICIs. These results support prior work, 6 which suggested no new or exacerbation of irAEs after administration of the Pfizer-BioNTech vaccine among 134 ICI-treated cancer patients. Further, after investigating the 152,748 adverse events in the VAERS, there were only six adverse events which were suspicious for irAEs following COVID-19 vaccine administration. Given the large number of patients receiving ICIs, this is likely consistent with the background rate of irAEs. However, the VAERS is limited by its passive reporting system and cannot be used to establish causal effects of a given vaccine, and cannot establish frequency data. Our study helps supplement the limited data available regarding the safety and risk of irAE of vaccination among patients with cancer receiving ICIs 7, 8 . Considering the high mortality rate from COVID-19 among cancer patients 1 , the benefit of COVID-19 vaccination exceeds the hypothetical increased risk of irAEs for patients receiving ICIs, which appears minimal or non-existent in this and other series. Limitations of this study include the retrospective nature, duration of follow up, and limited sample size. In summary, the current findings support major society guidelines to offer COVID-19 vaccines to cancer patients receiving ICIs 2-4 . 

Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study

(NCCN) NCCN. NCCN: Cancer and COVID-19 Vaccination

Annals of oncology : official journal of the European Society for Medical Oncology

Short-term safety of the BNT162b2 mRNA COVID-19 vaccine in patients with cancer treated with immune checkpoint inhibitors

Vaccination and Immune Checkpoint Inhibitors: Does Vaccination Increase the Risk of Immune-related Adverse Events? A Systematic Review of Literature

Influenza vaccination in cancer patients receiving immune checkpoint inhibitors: A systematic review

☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.☐The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:J o u r n a l P r e -p r o o f