The ASH Research Collaborative COVID-19 Registry for Hematology provides up-to-date information on outcomes and the course of illness for a group of patients with hematologic malignancies and COVID-19. In general, registry data showed that hematologic malignancies increase the risk of severity of COVID-19 and associated mortality. Using the data, researchers also identified risk factors for more severe COVID-19, such as older age, more advanced disease, pre–COVID-19 prognosis, and decision to forgo treatment in the intensive care unit (ICU). The current registry data were presented by William A. Wood, MD, MPH, and colleagues at the 2020 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 215).

William A. Wood, MD, MPH

“Patients with hematologic malignancies are at increased risk for adverse COVID-19 outcomes and are thus medically vulnerable. The registry data show that risks are greatest in those who are older, have advanced disease [cancer] or limited prognosis, and forgo ICU management; but keep in mind that the risks of COVID-19 are not trivial for others with hematologic malignancies,” said lead author Dr. Wood, of the University of North Carolina at Chapel Hill.

Because of the rapidly evolving landscape during the COVID-19 pandemic, relevant data from clinical trials are harder to come by. Data from the ASH registry (and others) are helpful in risk stratification of patients, planning for resource allocation, and for designing future clinical trials.

“As data accumulate, we will be able to ask and answer other questions about treatments and risk factors,” Dr. Wood added.

As of December 2020, the global COVID-19 pandemic has affected more than 50 million people worldwide and more than 11 million in the United States. The viral infection is especially risky for immunocompromised people, such as those with underlying cancers, “especially hematologic malignancies,” emphasized Dr. Wood.

“Patients with hematologic cancer are [already] at risk for greater illness severity and higher mortality due to aging, underlying hematologic disease, and underlying immune dysregulation due to the disease and/or its treatments. The concern is that COVID-19 infection could elevate this script,” he noted.

Background

The first reports from China on COVID-19 infection suggested that the risk of adverse outcomes was higher in patients with cancer, with mortality approaching 40%. Primary care administrative data also suggested a higher risk of death associated with cancer and COVID-19. This led to launching several registries to focus on cancer and COVID-19.

In this context, the ASH Research Collaborative COVID-19 Registry for Hematology was undertaken to report on COVID-19–positive patients with hematologic malignancies and underlying hematologic conditions, or post–COVID-19 hematologic complications.

Dr. Wood’s presentation at the ASH Annual Meeting focused only on hematologic malignancies and COVID-19.

Registry Findings

Dr. Wood reported data on 656 patients worldwide, 396 from North America. All data entered in the registry are submitted by individuals or by institutions. The data are de-identified, have a central Institutional Review Board exemption, and are General Data Protection Regulation–compliant.

Overall, 77% of patients were older than age 40; 60% were male; and among those who reported ethnicity, 43% were White, 27% were Asian, 17% were Hispanic or Latino/Latina, and 13% were Black.

More than half (57%) of the patients had comorbidities; the two most frequently reported were diabetes (30%) and hypertension (50%). Of patients who reported smoking status, 31% were current or former smokers.

Regarding cancer types, 57% had leukemia, 25% had lymphoma, and 18% had plasma cell neoplasms. Pre–COVID-19 infection, 80% of those entered on the registry had an expected prognosis of more than 12 months.

Common COVID-19–related symptoms were fever, cough, shortness of breath, and fatigue, and this was true in both hospitalized patients and those who did not require hospitalization. About 50% of patients received COVID-19­–directed therapy, including azithromycin and hydroxychloroquine.

Mild COVID-19 infection (ie, in outpatients) occurred in 225 patients, the vast majority of whom recovered. Among those with moderate COVID-19 infection meriting hospitalization, 196 recovered and 32 died. Among those with severe COVID-19 infection (requiring ICU stay), 47 recovered and 89 died.

The overall death rate for all patients with hematologic malignancies was 20%, which is much higher than the 2% case fatality rate for the U.S. population, according to the Johns Hopkins Coronavirus Resource Center. Mortality rate was greater (33%) in hospitalized patients or those in ICU care.

Factors Associated With Severity of Infection

No differences in COVID-19 severity were associated with sex, race, or ethnicity.

More than 70% of those with moderate to severe COVID-19 disease had diabetes or hypertension. The rates of moderate to severe COVID-19 infection among patients with leukemia, lymphoma, or plasma cell disorders ranged from 61% to 65%.

In the year prior to diagnosis, more than 65% of all patients received cytotoxic chemotherapy, immunotherapy, targeted therapy, and/or other cancer-directed treatment. Moderate to severe COVID-19 infection was reported in 69% of those undergoing initial cancer treatment compared to 50% in remission and 79% with relapsed or refractory cancer.

The mortality rate was 51% among those with a pre–COVID-19 prognosis life expectancy of less than 12 months, and 13% in those with a pre–COVID-19 life expectancy greater than 12 months.  

Mortality also differed across malignancy status, at a rate of 21% for those in initial cancer treatment, 13% for those in remission, and 36% for those with relapsed/refractory hematologic cancer.

Overall, 52% of patients with severity data (n = 555) had moderate to severe COVID-19, and severity increased with age: among moderate COVID-19 cases, 8 occurred in patients younger than age 19; 24 occurred in patients between the ages of 19 and 39; 95 occurred in patients between the ages of 40 and 69; and 43 occurred in patients older than 69. Eight deaths were reported among those aged 40 to 69 with moderate COVID-19, and 14 deaths occurred in those older than 69 with moderate infection.

The rate of severe COVID-19 was very low in patients younger than age 19 and low in patients between the ages of 19 and 39. For those aged 40 to 69, 26 recovered; 8 died with palliative care only, and 37 died with full medical care. For those older than 69 with severe COVID-19, 13 recovered, 17 died with palliative care only, and 18 died with full medical care.

“An important factor affecting outcome was choice to forgo ICU care, and this choice was strongly associated with age,” emphasized Dr. Wood.

Among those who declined ICU care, the death rate was 73%, while it was 13% among those who opted for ICU care. The decision to forgo ICU care differed according to physician-estimated pre–COVID-19 prognosis. Only 6% of those with a preprognosis of greater than 12 months chose to forgo ICU care, compared with 28% of those with a shorter prognosis (ie, < 12 months).

Malignancy status also was related to the decision to forgo ICU care, with almost four times as many people with relapsed or refractory cancer declining compared to 6% of those in remission.

Pre–COVID-19 prognosis was also related to severity of COVID-19: those with shorter prognosis were significantly more likely to have moderate to severe infection compared to those with a greater than 12-month preprognosis: 79% vs 58%, respectively.

In addition, the recorded death rate among patients has improved—dropping from 28%, which was seen among the first 250 patients, to 20% with more cases included in the present analysis. Dr. Wood explained that while this may represent true improvements in outcomes over time, this cannot be stated with certainty as the precise dates of diagnosis were not recorded due to the de-identified nature of the registry data.

The Future

Data collection for the ASH Registry is ongoing, and now the registry supports batch data submission.

“We welcome submissions by individuals and institutions and are happy to answer any questions. With more data, the power of the registry to inform decisions will grow. The ASH Research Collaborative Data Hub will also collect COVID-19 data and can be leveraged for surveillance testing and vaccine distribution in vulnerable populations. We encourage data submission and welcome participation from all of you,” Dr. Wood told listeners. “Visit www.ashrc.org to learn about the registry and data hub, to view real-time graphic COVID-19 registry display, and to submit data.”

Commentary

Stephanie Lee, MD, MPH

ASH President Stephanie Lee, MD, MPH, Associate Director of the Clinical Research Division of Fred Hutchinson Cancer Research Center and Professor at the University of Washington, Seattle, congratulated the investigators on this extensive effort to collect real-world data to inform clinical practice on COVID-19 in patients with hematologic cancers.

“This study is an example of trying to harness real-world information until we have more controlled studies. The ASH Research Collaborative Data Hub collected real-world data on people with lab-confirmed COVID-19 presumptive infections and hematologic cancers from 74 sites. These are people with heterogeneous cancer. The overall mortality rate was … higher if the patient’s pre-COVID prognosis was less than 12 months or if patients had advanced disease,” commented Dr. Lee.

Disclosure: For full disclosures of the study authors, visit ash.confex.com.