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Mepolizumab in patients with lymphoid-variant hypereosinophilic syndrome: A multicenter prospective study

par Catherine, Julien ;Karimi, Sina ;Dewispelaere, Laurent ;Lelubre, Christophe ;Schandené, Liliane ;Roufosse, Florence
Référence Journal of allergy and clinical immunology
Publication Publié, 2025-01-01

Article révisé par les pairs

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Résumé :

Background: Hypereosinophilic syndrome (HES) is characterized by blood and tissue hypereosinophilia causing organ damage and/or dysfunction. Mepolizumab, an anti–IL-5 antibody, has recently been approved in this indication. In lymphoid-variant HES, eosinophil expansion is driven by IL-5–producing clonal CD3−CD4+ T cells. Objective: This study aimed to elucidate the efficacy of mepolizumab in patients with CD3−CD4+ lymphoid-variant HES, and the effect of treatment on aberrant cells and associated biomarkers. Methods: A biomarker substudy was conducted during 2 clinical trials evaluating mepolizumab in HES, a 32-week randomized placebo-controlled trial (200622) followed by a 20-week open-label extension (205203). Patients with CD3−CD4+ and/or clonal T cells, elevated serum TARC/CCL17, soluble (s)CD25, and/or detectable IL-5 were identified, and their treatment responses were compared to those without these anomalies. Results: Of the 108 patients enrolled onto 200622 and 205203, 103 consented to the study, including 17 with a CD3−CD4+ T-cell subset. Presence of CD3−CD4+ T cells or serum sCD25 levels ≥1500 pg/mL was associated with reduced eosinophil-lowering and corticosteroid-sparing effects of mepolizumab. None of the biomarkers was associated with an increased likelihood of experiencing clinical flares. A mepolizumab-induced increase in serum IL-5 was observed that was significantly higher in patients with CD3−CD4+ T cells. Treatment did not affect CD3−CD4+ T-cell counts. Conclusion: Mepolizumab has a favorable effect on disease flares in patients with CD3−CD4+ lymphoid-variant HES, although reduced eosinophil-depleting and corticosteroid-sparing effects are observed at the currently approved dose. Further studies are needed to validate these findings on larger patient cohorts, and to explore whether clinical activity other than flares is equally controlled in this disease variant.