Dataset Information

Association of Thrombosis With Hypereosinophilic Syndrome in Patients With Genetic Alterations.

ABSTRACT:

Importance

Hypereosinophilic syndromes (HESs) are a rare group of disorders that result in overproduction of eosinophils, leading to tissue damage. Thrombotic complications in HES and associated risk factors in this patient population have not been extensively studied.

Objective

To investigate the rates of and risk factors associated with thrombotic events in patients with HES, including markers of clonal hematopoiesis as evidenced by molecular aberrations on next-generation sequencing.

Design, setting, and participants

This retrospective cohort study evaluated patients seen at Brigham and Women's Hospital and Harvard Medical School in Boston, Massachusetts, from January 1, 2015, to January 1, 2020. Patients who had hypereosinophilia with an absolute eosinophil count of 1500 cells/μL or greater on 2 separate occasions at least 1 month apart and who underwent genetic or molecular testing as part of their work-up were included. Patients with secondary eosinophilia were excluded.

Main outcomes and measures

Symptomatic and asymptomatic arterial and venous thrombotic events after the diagnosis of HES and all-cause death.

Results

A total of 71 patients (median age, 58 years [interquartile range (IQR), 43-67 years]; 36 women [51%]; 57 White patients [80%]) were included. Patients had a median follow-up time of 29 months (IQR, 19-49 months). Seventeen patients (24%) had 1 or more thrombotic events, including 11 venous thromboembolic events and 11 arterial thrombotic events (8 patients had ≥1 event and 3 patients had recurrent events). Patients with 1 or more thrombotic events had a higher median Eastern Cooperative Oncology Group performance status (median, 1 [IQR, 1-2] vs 0 [IQR, 0-1]; P = .002), had more frequent cardiac involvement (7 of 17 events [41%] vs 6 of 54 events [11%]; P = .01), more frequently received treatment (17 of 17 events [100%] vs 40 of 54 events [74%]; P = .02), and had more molecular aberrations on next-generation sequencing (12 of 17 [71%] vs 12 of 54 [26%]; P = .003) vs patients without thrombosis. After multivariable analysis, the presence of molecular aberration was associated with increased odds of thrombosis (adjusted odds ratio, 5.4; 95% CI, 1.1-27.7). Death occurred more frequently in patients with thrombotic events compared with those without (6 of 17 [35%] vs 2 of 54 [4%]; P = .002) and in patients with molecular aberrations compared with those without (6 of 24 [25%] vs 1 of 40 [3%]; P = .009), although only thrombotic events were significantly associated with increased odds of death after multivariable analysis.

Conclusions and relevance

In this cohort study, thrombosis was common in patients with HES and was significantly associated with increased risk of death.

SUBMITTER: Leiva O

PROVIDER: S-EPMC8346937 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundCurrent standard-of-care treatments for hypereosinophilic syndrome (HES) include oral corticosteroids (OCS) and immunosuppressive/cytotoxic (IS/CT) therapies. The anti-IL-5 monoclonal antibody mepolizumab has also recently been approved for patients with this disease. The objective of this analysis was to assess the relationship between baseline therapy and flare reduction in patients with HES treated with mepolizumab, using data from the Phase III 200622 study (NCT02836496).MethodsIn the double-blind, parallel-group 200622 study, eligible patients were ≥12 years old and had HES for ≥6 months, ≥2 flares in the previous 12 months, blood eosinophils ≥1000 cells/μL at screening and ≥4 weeks' stable HES therapy. Patients were randomised (1:1) to receive mepolizumab 300 mg subcutaneously or placebo every 4 weeks for 32 weeks plus their existing HES therapy. This post hoc, descriptive analysis assessed the effect of baseline HES therapy [IS/CT (± OCS), OCS No IS/CT, and No IS/CT/OCS] on the proportion of patients with ≥1 flare during the study period, the annualised rate of flares, time to first flare, and the proportion of patients with ≥1 flare during Weeks 20─32, with mepolizumab versus placebo.ResultsMepolizumab treatment was associated with a decrease in the proportion of patients who experienced ≥1 flare during the study period in all baseline therapy groups versus placebo (32-96% reduction). Similarly, the probability of a flare was lower with mepolizumab (14.3-31.4%) than placebo (35.7-74.1%) in all baseline therapy groups, as was the annualised flare rate (0.22-0.68 vs 1.14-1.62). The proportion of patients who experienced ≥1 flare during Weeks 20-32 was reduced with mepolizumab versus placebo for all baseline therapy groups (55-85% reduction). For all endpoints, the greatest effect of mepolizumab treatment was seen in the IS/CT (± OCS) group.ConclusionsPatients with poorly controlled HES are likely to achieve clinical benefit with mepolizumab in terms of flare reduction, regardless of their baseline therapy.Clinical trial registration(https://clinicaltrials.gov/ct2/show/NCT02836496).