Outcomes of COVID-19 in patients with CLL: a multicenter international experience

Abstract

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.

Clinical characteristics and risk factors associated with COVID-19 severity in patients with haematological malignancies in Italy: a retrospective, multicentre, cohort study

“…Our data did not indicate a clear protective or adverse effect of Bruton TKI therapy, as reported by Mato and colleagues. 31 Limitations of our study include the retrospective nature of the study, the lack of power to support firm conclu sions, the heterogeneity of haematological malignancies included, and potential issues with generalisability to nonhaematological malignancies, benign haematological disorders, or cancer. We did not include patients who were asymptomatic or were not tested for SARS-CoV-2 infection (during February and March, routine swab testing of asymptomatic people was not allowed by the Italian Government), which is likely to have resulted in a higher mortality rate in our cohort.…”

“…Our data did not indicate a clear protective or adverse effect of Bruton TKI therapy, as reported by Mato and colleagues. 31 …”

Ibrutinib for chronic lymphocytic leukemia in the setting of respiratory failure from severe COVID‐19 infection: Case report and literature review

“…Surveying 62 CLL specialists, Koffman et al found that only 44% of experts favored unconditional continuation of treatment for COVID‐19 patients in the outpatient setting and down to 32.5% in non‐ICU inpatients [7]. Mato et al noted that patient with CLL who were receiving BTK inhibitors and diagnosed with COVID‐19 had similar survivals (34%) compared with patients who did not receive BTK inhibitors (35%); however, 79% of patients had their BTK inhibitor held at the time of symptomatic COVID‐19 diagnosis [8]. Most of the discontinuation decisions were due to concerns of the increased infections risks with BTK inhibitor use.…”

When CLL meets COVID-19

“… In this issue of Blood , report an international, multicenter analysis of 198 patients with chronic lymphocytic leukemia (CLL) and symptomatic COVID-19. 1 In this analysis, COVID-19 appears to be more severe in CLL patients than in the general population and, although risk factors are the same as for the general COVID-19 population, the outcome of patients needing admission is poor, with a case fatality rate of 37%. The Mato et al paper is particularly compelling as reports of COVID-19 in specific diseases are needed, particularly in cancer where COVID-19 adds to the physical and emotional distress these patients already suffer.…”

“…The case fatality rate observed in 2 studies analyzing the impact of COVID-19 in CLL patients is ∼37%. 1 , 4 …”