Clinical Challenge: Hematologic Malignancy and COVID-19

As the COVID-19 pandemic continues to pose a threat to global health and well-being, physicians treating patients with cancer, particularly those with hematologic malignancies, must address the additional challenges posed by infection with SARS-CoV-2.

“Patients with hematologic malignancy appear to be susceptible to higher mortality from COVID-19 than has been reported in the general population,” said Lisa K. Hicks, MD, of St. Michael’s Hospital in Toronto, Canada. “However, importantly, most people with blood cancer who are infected with SARS-CoV2 will survive the infection,” she told MedPage Today.

Many questions remain unanswered, said Hicks, who is chair of the Committee on Quality of the American Society of Hematology (ASH) — for example, whether specific types of hematologic malignancy are uniquely susceptible to serious outcomes from COVID-19; and whether COVID-19 vaccination will be protective, particularly in patients who are profoundly immunosuppressed as a result of cytotoxic cancer treatments.

The ASH Research Collaborative (RC) COVID-19 Registry for Hematology opened on April 1, 2020, as a worldwide resource for physicians. Currently, it holds descriptive data on subtypes, stages, symptoms, and outcomes in more than 1,000 patients of all ages.

The inaugural report, published in Blood Advances, is based on an analysis of the first 250 patients with both hematologic malignancy and COVID-19 registered from 74 countries, as of July 8, 2020. Hicks is a co-author, and along with William A. Wood, MD, MPH, of the University of North Carolina at Chapel Hill, conceived of and designed the global database for the registry.

The analysis revealed that 33% of patients had acute leukemia, 27% had non-Hodgkin lymphoma, and 16% had been treated for myeloma or amyloidosis. The most frequent presenting symptom was fever (occurring in 73% of the patients) followed by cough (67%), dyspnea (50%), and fatigue (40%).

The overall mortality rate was 28% and increased to 42% among patients with COVID-19 severe enough to require hospitalization. The highest rates of morbidity and mortality were seen in patients who were older, had relapsed/refractory disease, had comorbidities such as hypertension and diabetes, and had a prognosis of less than 12 months at the time of COVID-19 diagnosis.

The findings “illustrate the importance of protecting this vulnerable population from COVID-19 exposure,” Hicks, Wood, and co-authors wrote.

Notably, the analysis showed that the mortality risk was heterogeneous and unpredictable based solely on risk factors such as patient age and underlying disease severity. For example, some older patients with a limited prognosis at the time of COVID-19 diagnosis did not develop severe disease and recovered, while 13% of patients under the age of 40 with a prognosis of more than 12 months did not.

The findings become particularly important when decisions have to be made about allocating limited resources and determining which patients receive intensive care. In 11 patients who were older and had a pre-COVID-19 prognosis of less than 12 months, for example, the decision against intensive care unit admission was a significant factor in the deaths of eight patients. And in 21 patients younger than 40 with a prognosis of more than 12 months at the time of COVID-19 diagnosis, 10 survived after receiving maximal supportive care, the team reported.

Understanding the predictors of survival in patients with cancer receiving intensive care can be challenging. “We have no data in our registry to inform the context within which ICU decisions were made, but given the prevalence of this practice pattern, we believe this is an important area for future research,” the authors wrote.

The development of vaccines for COVID-19 has been a major advance, Hicks noted, adding that the ASH registry has been updated to capture vaccination status. “One big unknown right now is whether or not people with blood cancer, particularly those on treatment, will be protected by COVID-19 vaccination. Registry data may shed some light on this question,” she said.

As treatment evolves, global data will continue to be collected and updated in real-time on a “rich, public-facing data dashboard,” Hicks continued. “Additional, multivariate analyses are ongoing, and we hope to have more information to share in the near future. It is our hope that the ASH RC COVID-19 Registry for Hematology will inform many types of research that can increase the understanding of how COVID-19 impacts patients with blood cancer.”

Similar findings were reported by a French research team based on a cohort study of 28 patients with hematologic malignancy and COVID-19 admitted to hospital between March 9 and April 4, 2020. The results showed that overall, the risk of severe COVID-19 with acute respiratory distress syndrome requiring mechanical ventilation was significantly increased when compared with the general population.

At 1 month, the mortality rate was 40%, and the researchers said they expected it to increase further as follow-up continued. “We must emphasize that more than half of the patients were over 65 years of age, and 92% had at least one additional comorbidity,” said Florent Malard, MD, of Hôpital Saint-Antoine of Sorbonne Université in Paris, and colleagues, writing in Bone Marrow Transplantation.

These factors have been previously associated with COVID-19 severity, and potentially “contributed to the seriousness of the infection and high mortality rate observed in our study,” the researchers explained.

The fact that fewer than half of the patients were receiving antineoplastic treatment at the time of COVID-19 diagnosis provides evidence for the long-term immunosuppressive effect of prior therapies, the investigators said. It also underscores the need for increased vigilance in every patient. Patients with malignant melanoma were over-represented in the study and may be particularly vulnerable.

In another report, a “care delivery review,” a team from the Seattle Cancer Care Alliance, Fred Hutchinson Cancer Research Center, and the University of Washington, presented recommendations for managing patients with hematologic malignancy during the pandemic.

“Seattle was home to the first patient diagnosed with COVID-19 identified in the United States,” wrote Mary-Elizabeth Percival, MD, and co-authors in JCO Oncology Practice. “During this dynamic time, our faculty have generated guidelines to best balance the risk of underlying malignancy with the risks of COVID-19 infection and mortality.”

The recommendations, dubbed “The Seattle Strategy,” cover general considerations and supportive care before taking a deep dive into the specifics of patient care for all lymphoid malignancies and myeloid neoplasms.