Patients With Hematologic Cancers at Increased Risk for Adverse COVID-19 Outcomes

William Wood, MD, MPH

Patients with hematologic malignancies are at increased risk for significant morbidity and mortality from coronavirus disease 2019 (COVID-19), and the risk of death appeared to be greatest in those who were older, had more severe infection, a poorer prognosis, or who decided to forego intensive treatment, according to updated data from the ASH Research Collaborative (RC) COVID-19 Registry presented during the 2020 ASH Annual Meeting & Exposition.¹

“Patients with hematologic malignancies are at increased risk for adverse COVID-19 outcomes and can thus be considered as a medically vulnerable population. We found that risks are greatest in those who are older, have advanced disease or a limited prognosis, and forego intensive management,” William Wood, MD, MPH, an associate professor at the University of North Carolina at Chapel Hill, said during a presentation of the data at the meeting. “As data in the registry accumulate, we will be able to ask and answer additional questions, such as those related to specific diseases, treatments, or risk factors.”

Findings revealed that 20% of the 656 patients included in the registry cohort died. Among patients who required hospital- or intensive care unit (ICU)–level care, the mortality rate was 33%; this rate was almost doubled in those with ICU-level severity, at 65%. The percentage of patients with leukemia, lymphoma, or plasma cell disorders who had moderate or severe disease proved to be similar and ranged from 61% to 65%.

Additionally, COVID-19 disease severity was found to be strongly associated with malignancy status at the time of diagnosis. Specifically, 69% of patients who were receiving initial treatment had moderate or severe disease compared with 50% of those in remission and 79% of those with relapsed or refractory disease.

Mortality rates were also found to significantly differ based on the patient’s prognosis. In patients who had a pre–COVID-19 prognosis of less than 12 months had a mortality rate of 51% compared with just 13% in those who had a pre-pandemic prognosis of over 12 months. Mortality rates also differed across malignancy status, going from 21% in those receiving initial treatment, to 13% in those who were in remission, to 36% in those with relapsed or refractory disease.

The proportion of patients with moderate or severe disease increased with age. Specifically, 47% of patients under the age of 19 years had moderate or severe disease compared with 43% of those who were 19 years to 39 years, 62% of those between the ages of 40 years and 69 years, and 70% of those who were 70 years of age or older. Increased age was also linked with higher mortality rates; these rates ranged from 5%, to 6%, to 18%, to 33% in those under 19 years, 19 to 39 years, 40 to 69 years, and 70 years and older, respectively.

Twelve percent of patients decided to forego ICU-level care and 90% of those patients had moderate or severe disease. The decision to forego ICU-level care was found to be associated with age. Forty-two percent of the deaths reported were those who had chosen to forego ICU care; only 4% of these patients recovered. Among those who declined ICU-level care, the mortality rate was 73% versus 13% in those who did not decline care.

“The ASH RC developed a COVID-19 Registry for Hematology in the early weeks of the pandemic,” said Wood. “Data are submitted by individuals or by individual institutions and submission at an institutional level is becoming more efficient and feasible.”

The ASH RC COVID-19 Registry for Hematology is a global reference tool;² it is a portion of the larger ASH RC Data Hub platform, which collects information on patients who have a hematologic disease and are infected with virus or those with a post–COVID-19 hematologic complication. The data are aggregated across several malignancies and are made available to public through a virtual dashboard.³

The registry was reviewed by the Western Institutional Board and was deemed to be human subjects research exempt; the effort was approved for a waiver of authorization. Moreover, all information collected are de-identified and comply with HIPAA Safe Harbor regulations and procedures are GDPR compliant.

Data from the first 250 patients were concurrently published in Blood Advances. At the meeting, Woods shared updated data collected from a total of 656 patients. The majority of the patients included in the analysis were from North America, although a significant number of patient data came from other areas across the globe.

Seventy-seven percent of patients were aged 40 years or older and more than half, or 60%, were male. With regard to race and ethnicity, 43% were White/Caucasian, 27% were Asian, 17% were Hispanic/Latino or Latina, and 13% were Black/African American.

Fifty-seven percent of patients had leukemia, 25% had lymphoma, and 18% had plasma cell neoplasms. Morbidities were reported in 57% of patients and the 2 most frequently reported comorbidities were hypertension and diabetes, which represented 50% and 30% of patients, respectively. Additionally, the majority of patients, or 80%, had an expected prognosis of greater than 12 months prior to the COVID-19 pandemic.

Of patients with reported smoking status, 31% were either current or former smokers. Eleven percent of patients did not have any reported symptoms. In those who were symptomatic, the most frequently reported symptoms included fever, cough, shortness of breath, and fatigue. “This was the same whether patients did or did not require hospitalization,” Wood noted. After 10 days from diagnosis, symptoms were ongoing in 60% of patients.

When taking a look at COVID-19–directed therapies, investigators found that azithromycin and hydroxychloroquine had been given to approximately half of patients.

Additional results showed no difference in disease severity by sex, race, or ethnicity. More than 70% of patients with moderate or severe disease had diabetes and/or hypotension. In the year before COVID-19 diagnosis, more than 65% of patients with moderate or severe disease had received cytotoxic chemotherapy, immunotherapy, targeted therapy, and/or other treatment.

Moreover, the decision to forego ICU-level care was found to significantly differ by prognosis. Of the patients who had an estimated pre–COVID-19 prognosis of more than 12 months per physician assessment, 6% decided to forego ICU-level care versus 38% of those with an estimated prognosis of less than 12 months.

Patients with an estimated pre–COVID-19 prognosis of 12 months or less were found to be significantly more likely to have moderate or severe disease versus those with a prognosis of greater than 12 months. Moderate or severe disease was observed in 79% of patients with a pre-pandemic prognosis of less than 12 months versus 58% in those with a pre–COVID-19 prognosis of more than 12 months.

“Where do we go from here? There are several ways in which we can use the momentum from the ASH RC COVID-19 Registry for Hematology to move forward together,” concluded Wood. “I want to emphasize the data collection in the registry is ongoing and we welcome and encourage data entered by individuals or institutions. With more data, the power of the registry to address questions that are of important to hematologists will [continue to] grow.”

References

1. Wood WA, Neuberg DS, Thompson JC, et al. Outcomes of patients with hematologic malignancies and COVID-19 infection: a report from the ASH Research Collaborative Data Hub. Presented at: 2020 ASH Annual Meeting & Exposition; December 5-8, 2020; Virtual. Abstract 215. https://bit.ly/36M8Nzj.
2. COVID-19 registry. ASH Research Collaborative. Accessed December 5, 2020. https://bit.ly/3huP7CG.
3. ASH RC Data Hub COVID-19 Registry for Hematology. ASH Research Collaborative. Accessed December 5, 2020. https://bit.ly/2JFRIy3.