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Given advanced age, comorbidities, and immune dysfunction, CLL patients may be at particularly high risk of infection and poor outcomes related to coronavirus disease-19 (COVID-19). Robust analysis of outcomes for CLL patients, particularly examining effects of baseline characteristics and CLL-directed therapy, is critical to optimally manage CLL patients through this evolving pandemic. CLL patients diagnosed with symptomatic COVID-19 across 43 international centers (n=198) were included. Hospital admission occurred in 90%. Median age at COVID-19 diagnosis was 70.5 years. Median CIRS score was 8 (range 4-32). Thirty-nine percent were treatment-naïve ("watch and wait") while 61% had received ≥1 CLL-directed therapy (median 2, range 1-8). Ninety patients (45%) were receiving active CLL therapy at COVID-19 diagnosis, most commonly BTK inhibitors (BTKi; n=68/90, 76%). At a median follow-up of 16 days, the overall case fatality rate (CFR) was 33%, though 25% remain admitted. "Watch and wait" and treated cohorts had similar rates of admission (89% vs. 90%), ICU admission (35% vs. 36%), intubation (33% vs. 25%), and mortality (37% vs. 32%). CLL-directed treatment with BTKi at COVID-19 diagnosis did not impact survival (CFR 34% vs. 35%), though BTKi was held during COVID-19 course for most patients. These data suggest that the subgroup of CLL patients admitted with COVID-19, regardless of disease phase or treatment status, are at high risk of death. Future epidemiologic studies are needed to assess SARS-CoV-2 infection risk, these data should be validated independently, and randomized studies of BTKi in COVID-19 are needed to provide definitive evidence of benefit.

Background Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. Results The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value < 0.0001). In the multivariable analysis, age, active malignancy, chronic cardiac disease, liver disease, renal impairment, smoking history, and ICU stay correlated with mortality. Acute myeloid leukemia was a higher mortality risk than lymphoproliferative diseases. Conclusions This survey confirms that COVID-19 patients with HM are at high risk of lethal complications. However, improved COVID-19 prevention has reduced mortality despite an increase in the number of reported cases.

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