Heightened but variable COVID-19 risks for patients with cancer

Four years into the coronavirus disease 2019 (COVID-19) pandemic, multiple studies have agreed that patients with cancer are more susceptible to COVID-19 infection and have a higher risk of worse outcomes than the general population. Large cohort studies have revealed plenty of nuances, however, while raising additional questions in need of better answers.

Some cancer types, such as hematologic malignancies, have been associated with a higher risk of poor COVID-19 outcomes, as have some treatment types, such as recent cytotoxic chemotherapies, as well as a long list of other demographic factors and comorbidities. Researchers are just starting to investigate the added danger of long COVID-19.

The data, however, have also provided some reassurances, says Noha Sharafeldin, MD, PhD, MSc, an assistant professor of medicine at the University of Alabama at Birmingham and an associate scientist at the university’s O’Neal Comprehensive Cancer Center. One of the most notable findings is that vaccination against the SARS-CoV-2 virus can reduce the risk of severe infection even among those with hematologic malignancies.

“I think the thing we know for sure, if, God forbid, we’re hit with something similar again, is that this should be a group of people who should be at the forefront of protection efforts because of so many factors working against them,” Dr Sharafeldin says. “But the flip side of it is that vaccines work in those patients. We shouldn’t think that these patients might not benefit from these kinds of interventions.”

In a study that predated the first COVID-19 vaccines, Dr Sharafeldin and her colleagues found that COVID-19 positivity as significantly associated with an increased risk of all-cause mortality in adult patients with cancer.¹ Within the subset of patients who had cancer and were positive for COVID-19, multiple comorbidities, male gender, an age of 65 years or older, a hematologic malignancy, multiple tumor sites, and cytotoxic therapy received up to 30 days before the COVID-19 diagnosis were all associated with a higher risk of all-cause mortality. Recently administered immunotherapies or targeted therapies, however, did not increase the risk.

Dr Sharafeldin says that the assessment provided a kind of early natural history of COVID-19. The study drew on the medical records of nearly 4.4 million patients in the National COVID Cohort Collaborative. At the time, no one was sure of how to account for COVID-19 vulnerability or diagnosed infections in patients with cancer, particularly those in need of a bone marrow transplant. The study allowed the researchers to quantify the overall risk and identify the most vulnerable subset of patients with cancer. As expected, Dr Sharafeldin says, patients with hematologic malignancies had the highest risk of all-cause death, which was explainable by their predisposition for greater immunodeficiency.

“One thing we solidified is that this group of patients remains the most vulnerable when we compare them to other groups of patients,” Dr Sharafeldin says. Immunocompromised patients in general are at high risk, she emphasizes, “but cancer is more pervasive in its effects on people across the age spectrum.”

In a separate study based on data reported to the COVID-19 and Cancer Consortium between mid-March and mid-November 2020, researchers similarly found that older age, male sex, hematologic malignancy, and recent chemotherapy were all associated with poor outcomes among patients with cancer and COVID-19.² The study also linked obesity, a host of other comorbidities, and certain laboratory measurements in hospitalized patients to poorer outcomes.

“Definitely, this makes the point that we need to be cognizant of that risk and we do need to educate patients and the community to achieve as much prevention as possible,” says the study’s lead author, Petros Grivas, MD, PhD, a professor in the Clinical Research Division at the Fred Hutchinson Cancer Research Center in Seattle, Washington. Dr Grivas, who is also the director of UW Medicine’s Genitourinary Cancers Program, notes that prioritizing vaccination in patients with cancer not only can reduce the risk of a COVID-19 infection but also can lower its severity.

Some studies have added nuances or raised questions about risks associated with specific anticancer interventions. One evaluation, for instance, found that patients who received any anticancer treatment up to 3 months before their COVID-19 diagnosis had an increased risk of death, intensive care unit admission, and hospitalization.³ (Recent chemotherapy and chemoimmunotherapy in particular were associated with worse outcomes.)

Conversely, patients with COVID-19 who received no recent cancer treatment within the same 3-month period had similar or better outcomes in comparison with patients without cancer. “This finding suggests that patients with cancer represent a heterogenous group, and risk stratification according to recent treatment and the treatment administered has important implications for patients, clinicians, and health care systems,” the authors concluded.

Importantly, however, the study showed that a full two-dose messenger RNA vaccination (which constituted the vast majority of vaccines administered at the time) lowered the risk of a breakthrough infection across the board, including patients with hematologic malignancies. “That’s what I think was the take-home message: Completing the two doses was the most protection we could get for cancer patients,” Dr Sharafeldin says.

A new report by the same group that focused on patients with both multiple myeloma and COVID-19 has further confirmed the protective effects of vaccination and blood or bone marrow transplants.⁵ Compared to unvaccinated patients with myeloma, their vaccinated counterparts were at 350% less risk of severe outcomes and 331% less risk of death after infection with COVID-19.

Risks associated with long COVID-19, although less well defined, are beginning to attract considerable attention. A poster presentation by Dr Sharafeldin’s group, conducted as medical institutions were just starting to set up specialized clinics, reported an overrepresentation of patients with cancer in a nationally representative sample of patients with long COVID-19.⁶ Within that patient sample, those with cancer were more likely to be older, have more comorbidities, and be hospitalized for COVID-19. Those findings, she says, point to additional contributing risk factors in need of further investigation.

Research has also consistently pointed toward significant racial and ethnic disparities in risk among patients who have both cancer and COVID-19. Work by the COVID-19 and Cancer Consortium and multiple other groups has further underscored risk factors such as the detrimental effects of unequal access to cancer care. “We want to bridge that gap and make sure that all people have adequate access to care, adequate vaccination, and adequate education,” Dr Grivas says. The COVID-19 pandemic compounded the risk by interfering with timely cancer screening, diagnosis, and treatment. As a result, he and his colleagues are seeing more advanced cancers in their patients.

Although some treatments such as cytotoxic chemotherapy might carry higher COVID-19–associated risks, Dr Grivas worries that patients who could benefit are not receiving these treatments at all. “We have to balance benefits and risks and, of course, take precautions,” he says.

The rapidly growing body of literature has, at the very least, pointed out some of the most vulnerable groups of patients who should be prioritized for protective measures such as vaccination. “When it comes to a cancer patient, I think we should just err toward overprotection until we know what works and what doesn’t work,” Dr Sharafeldin says.