Increased risk for adverse outcomes in patients with haematologic malignancies and COVID-19 infection
Data from the ASH Research Collaborative COVID-19 Registry for Hematology support the emerging consensus that patients with haematologic malignancies experience significant morbidity and mortality from a COVID-19 infection. Particularly patients with an estimated prognosis of less than twelve months at the time of their COVID-19 diagnosis and patients with a relapsed/refractory disease are at increased risk for experiencing moderate or severe COVID-19 disease and COVID-19 related death. The registry also revealed that several deaths occurred after a decision was made to forego on intensive care in favour of a palliative approach.
Background
COVID-19, resulting from the SARS-CoV-2 infection, emerged late 2019 and was declared a global pandemic in March 2020. Patients with underlying haematologic malignancies might be a medically vulnerable population for adverse outcomes following COVID-19 infections, because of various reasons such as advanced age or comorbidities including hypertension and diabetes. Therefore, the ASH Research Collaborative COVID-19 Registry for Hematology was developed, to study features and outcomes of a COVID-19 infection in patients with underlying blood disorders, such as haematologic malignancies. The Registry opened for data collection on April 1st, 2020. Although the Registry collected data for all underlying blood disorders, data presented at ASH 2020 were limited to patients with malignant haematologic diseases. In total, data from 656 patients were included in the analysis, with the majority of them originating from North America (N=396).
Results
Overall, 77% of patients in the registry were 40 years or older and 60% were male. In 57% of patients, comorbidities were reported. The two most common comorbidities were diabetes (30%) and hypertension (50%). In total, 57% of patients had leukaemia, 25% had lymphoma and 18% had plasma cell neoplasms. Eighty percent of patients were predicted pre-COVID to have a survival greater than twelve months. The most frequently reported symptoms were fever, cough, shortness of breath and fatigue, regardless of whether patients did or did not require hospitalisation. Azithromycine or hydroxychloroquine were used in about half of the patients.
COVID infections were classified as mild (outpatient-level severity), moderate (hospitalization-level severity) or severe (intensive care unit [ICU]-level severity). The overall death rate among patients with haematological malignancies and COVID-19 was 20%. Importantly, patients with mild disease represented 38% of the entire cohort and among these patients only two deaths were reported. For patients with moderate or severe disease, however, the death rate was much higher at 33%. There were no differences in disease severity by sex, race or ethnicity. In contrast, COVID-19 severity was strongly associated with the haematological malignancy status at the time of the diagnosis. Death rates differed significantly by prognosis, with 51% mortality in those patients with a pre-COVID prognosis of less than twelve months and 30% in those with pre-COVID life expectancy of greater than twelve months. Furthermore, patients with a prognosis of less than twelve months were significantly more likely to have moderate or severe disease as compared to those with a prognosis of more than twelve months.
Overall, 62% of patients had moderate or severe disease and this proportion increased with age. Age was also significantly associated with death, with death rates ranging from 5% and 6% in the two youngest age categories (below 19 years and 19-39 years, respectively) to 18% in patients between 40-69 years and 33% in patients aged 70 years or above. Of note, some patients decided to forego on a more intensive treatment strategy and of these patients 90% had moderate or severe disease. This choice to forego on more intensive therapy was strongly associated with age. The death rate among patients who opted to forego intensive care was 73% while the death rate was only 13% for those who did not decline more intensive therapy. How often the decision was made to forego a more intensified treatment differed significantly by prognosis; 6% in patients with a pre-COVID prognosis of more than 12 months, compared to 38% for those who had a prognosis of less than twelve months. In addition, the decision was also dependent on malignancy status; an intensified treatment was not deployed for 6% of patients in remission, 13% for those receiving initial treatment, 11% for those with stable disease and 27% for those with relapsed or refractory disease.
Conclusions
Patients with haematologic malignancies are at increased risk for adverse COVID-19 outcomes. Risks are greatest in patients who are older, in patients with advanced disease and in patients with a more dismal prognosis. Outcomes were also worse in patients who foregoed intensive management. As such, there seems no reason to withhold intensive therapies from patients with underlying haematologic malignancies and favourable prognoses, if aggressive supportive care is consistent with patient preferences. Data collection in the ASH RC COVID-19 registry is ongoing and now supports batch data submissions. The Registry has been expanded to include non-malignant haematologic diseases, and the Registry will continue to accumulate data as a resource for the haematology community.
Reference
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 ASH 2020; Abstract 215.
