Data Hint COVID-19 Vax May Improve Immunotherapy Efficacy in Some

Nancy A. Melville

November 21, 2022

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

While studies have generally alleviated concerns that COVID-19 vaccination could compromise the effects of immune checkpoint inhibitors, new research offers a twist: COVID-19 vaccination could improve outcomes for certain patients with cancer.

Specifically, compared with nonvaccinated patients, vaccinated patients with advanced nasopharyngeal cancer showed higher objective response rates and disease control rates after anti-PD-1 therapy and similar rates of severe immune-related adverse events.

The Sinovac COVID-19 vaccine included in the analysis is an inactivated vaccine developed in China. It has been endorsed for emergency use by the World Health Organization and approved in dozens of countries, though not in the United States.

Overall, the study suggests that "the efficacy of combination of anti-PD-1 treatment and chemotherapy was significantly improved for vaccinated nasopharyngeal cancer patients," the authors write.

First author Jian Li, MD, of the University Hospital Bonn, Germany, told Medscape Medical News that the results were indeed "a surprise."

Given the promising outcomes associated with COVID-19 vaccination in patients receiving anti-PD-1 therapy, this study may be "valuable to clinicians and other people who are dealing with nasopharyngeal cancer," Li added.

But the authors also expressed caution about the findings, even entitling the article: "Potentially improved response of COVID-19 vaccinated nasopharyngeal cancer patients to combination therapy with anti-PD-1 blockade and chemotherapy."

The analysis was published online last month in Annals of Oncology.

Experts have raised concerns about whether anti-PD-1 treatment might interfere with COVID-19 vaccination in patients with nasopharyngeal cancer, given that both COVID-19 and nasopharyngeal cancer affect the upper respiratory tract.

Li and colleagues have previously found that patients with metastatic lung, liver, or intestinal tract cancers receiving PD-1 inhibitors had no significant differences in outcomes after COVID-19 vaccination, and wanted to extend their research to patients being treated for nasopharyngeal cancer.

The authors evaluated 1537 patients with nasopharyngeal cancer who were enrolled at 23 hospitals in China from January 2021 and followed through to June 2022.

All patients — who were mostly men with a median age of 45 years — had a recurrent metastatic stage of cancer, and most were receiving concomitant anti-PD-1 therapy along with chemotherapy. About one quarter of patients (n = 373) had received the Sinovac COVID-19 vaccine and started anti-PD-1 therapy a median of 105 days after vaccination (range, 24-154 days). The remaining 75.7% of participants were not vaccinated against COVID-19.

Overall, 140 patients (9%) achieved complete remission during the study period, 503 (32.7%) had partial remission, 526 (34%) achieved stable disease, and 337 (22%) had progressive disease.

Compared with the non-vaccinated subgroup, vaccinated patients showed a significantly higher objective response rate (59.0% vs 38.8%) and disease control rate (80.2% vs 74.7%) following anti-PD-1 treatment.

Vaccinated patients were more likely to experience mild immune-related adverse events (73.6% vs 60.1%; P < 0.001), but not severe immune-related adverse events.

In a propensity score analysis of 1119 patients, the researchers matched patients according to age, gender, Karnofsky performance status, and body mass index, and observed similar results.

Compared with the non-vaccinated subgroup, vaccinated patients had a significantly higher objective response rate (59.0% vs 35.7%) and disease control rate (80.2% vs 72.5%), but similar rates of severe immune-related adverse events (4.9% vs 4.1%; P = .482).

Although the potential association between COVID-19 vaccination and increased efficacy of anti-PD-1 therapy in recurrent metastatic nasopharyngeal cancer is "interesting," the finding "needs to be validated in a larger cohort study," Li and colleagues conclude.

In addition, the mechanism underlying the findings remains unclear and would need to be elucidated in further studies. The authors proposed a few possible explanations, including that "exhausted CD8+ T cells could be reactivated in the tumor microenvironment during vaccination, facilitating immunotherapy."

Alexandre Malek, MD, who was not involved in the research, shared the authors' cautious optimism.

The findings are "promising," but "the hypothesis needs further in-depth investigation at the granular level to generalize and validate the results," said Malek, who is assistant professor of medicine in the Division of Infectious Diseases, Louisiana State University Health Shreveport.

Malek pointed to "a growing number of preclinical studies evaluating the role of vaccines as adjunct to immunotherapy to overcome cancer resistance by converting cold tumors to hot."

That research includes a study of a seasonal influenza vaccine and another of adenoviral based-vaccines.

It's also possible that vaccination against human papillomavirus (HPV) could benefit patients with nasopharyngeal cancers — many of which are associated with HPV, Malek noted.

"Novel anti-cancer therapies are underway to tackle HPV-positive nasopharyngeal cancer by using immune checkpoint inhibitors along with HPV vaccine as a way to enhance antitumor activity," Malek explained.

Given this, a key limitation of the current study is the lack of information on rates of viral-driven nasopharyngeal cancer, specifically HPV versus Epstein-Barr virus, he noted.

Still, the study "constitutes burgeoning data to unlock the role of new vaccines as adjunct to anti-cancer therapies, primarily immune checkpoint inhibitors, to promote and optimize immunogenicity and overcome tumor resistance," Malek said.

The study was funded by the Sino-German Center for Research Promotion (SGC), the DFG Cluster of Excellence ImmunoSensation², and the German Federal Ministry of Education and Research (BMBF). The authors and Malek have reported no relevant financial relationships.

Ann Oncol. Published online October 6, 2022. Full text

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