Prior treatment with PD-1 blockade did not influence the severity of COVID-19 in patients with lung cancer, according to a new study. The work published in Cancer Discovery1 looked at 69 outpatients with lung cancer who were diagnosed with COVID-19 during a 1-month period between March and April 2020 in New York.

Patients with cancer have a higher risk of developing severe COVID-19 and higher mortality rates,2,3 but little is currently known about the effect of specific therapies on this risk. There have been some concerns that the immunomodulatory effect of PD-1 blockade may influence the response of patients with cancer to COVID-19.

“We generally don’t think immune checkpoint inhibitors suppress the immune system and predispose patients to infection, but there are a few toxicities these people can develop, which may impact their ability to fight infections such as coronavirus,” said Mark Awad, MD, PhD, clinical director of the thoracic oncology treatment center at Dana-Farber Cancer Institute and assistant professor of medicine at Harvard Medical School, Boston, Massachusetts.

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One hypothesis is that the drugs could augment the hyperactive immune response seen in some patients, leading to severe disease.

“Immune checkpoint blockade is revolutionary for us, even for metastatic lung cancer; we are seeing 20% 5-year survival or longer,” said Ravi Salgia, MD, PhD, professor and chair, department of medical oncology and therapeutics research at City of Hope Cancer Center in Duarte, California. “But we can see cytokine releases from use of these therapies, which cause shortness of breath, coughing, and pneumonitis,” Dr Salgia added.

Cytokine storms and various inflammatory conditions have been frequently seen in severe, hospitalized cases of COVID-19, as well as in pneumonitis.

“The similarities here concern us. If something else compromises lung function in our patients, the consequences could be serious,” said Dr Salgia.

Two thirds of the patients with lung cancer in the study had previously received PD-1 blockade with a median time of last dose before COVID-19 diagnosis being 45 days. The research found no significant differences in severity of COVID-19 related to previous PD-1 blockade exposure.

“I think it is challenging in a small cohort of 69 patients — kudos to the authors for compiling these data in a very difficult research environment — but I do think there are limitations, for example, 41 of the 69 [patients] had prior PD-1 blockade, and there was a large range to the last dose,” said Dr Awad.

The patients who received PD-1 blockade had received it between 4 and 820 days before their COVID-19 diagnosis, and the researchers split up these patients into groups to try and analyze how more or less recent PD-1 therapy might influence responses. These groups were those who never received PD-1 blockade, people who had the most recent dose within 6 months, within 6 weeks, or who had their first dose within 3 months. However, the study found no consistent trends or differences in COVID-19 severity between these groups.

“There are a lot of variables in the treatment histories and medications they may have received for coronavirus treatment, so it is really difficult to make conclusions, even with the adjustments they made for these considerations,” said Dr Awad. “I’d be surprised to see striking differences between these cohorts in a heterogeneous patient population.”

Considering the high frequency of comorbidities in patients with lung cancer and other factors such as smoking history, which may independently affect COVID-19 outcomes, are these patients really the most suitable suitable population to interrogate about whether immune checkpoint inhibitors affect PD-1 responses?

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“It’s not a bad patient population at all; it’s a realistic population. Patients with cancer sometimes got cardiovascular events, [chronic obstructive pulmonary disease], smoking history, hypertension, diabetes — everything plays an important role, but combined epidemiologic studies are needed to really look at how these affect outcomes,” said Dr Salgia.

Approximately 25% of the hospitalized patients with lung cancer and COVID-19 died, which is higher than in the general population and similar to those with recognized comorbidities that predispose them to higher risk of COVID-19–related mortality.

“This is quite startling, and perhaps this is even the greater take-home message from this study than the immune checkpoint inhibitor results: This may be a particularly vulnerable population,” said Dr Awad.