Mepolizumab as a corticosteroid-sparing agent in lymphocytic variant hypereosinophilic syndrome

Abstract

Background: Mepolizumab, a monoclonal anti-IL-5 antibody, is an effective corticosteroid-sparing agent for patients with Fip1-like 1/platelet-derived growth factor receptor α fusion (F/P)-negative hypereosinophilic syndrome (HES). Lymphocytic variant hypereosinophilic syndrome (L-HES) is characterized by marked overproduction of IL-5 by dysregulated T cells.

Objective: To determine whether patients with L-HES respond to mepolizumab in terms of corticosteroid tapering and eosinophil depletion to the same extent as corticosteroid-responsive F/P-negative patients with HES and a normal T-cell profile.

Methods: Patients enrolled in the mepolizumab trial were evaluated for L-HES on the basis of T-cell phenotyping and T-cell receptor gene rearrangement patterns, and their serum thymus-and-activation-regulated chemokine (TARC) levels were measured. Response to treatment was compared in patient subgroups based on results of these analyses.

Results: Lymphocytic variant HES was diagnosed in 13 of 63 patients with HES with complete T-cell assessments. The ability to taper corticosteroids on mepolizumab was similar in patients with L-HES and those with a normal T-cell profile, although a lower proportion of patients with L-HES maintained eosinophil levels below 600/μL. Increased serum TARC levels (>1000 pg/mL) had no significant impact on the ability to reduce corticosteroid doses, but a lower proportion of patients with elevated TARC achieved eosinophil control on mepolizumab.

Conclusion: Mepolizumab is an effective corticosteroid-sparing agent for patients with L-HES. In some cases however, eosinophil levels remain above 600/μL, suggesting incomplete neutralization of overproduced IL-5 or involvement of other eosinophilopoietic factors.

Trial registration: ClinicalTrials.gov NCT00086658.

Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Figures

Figure 1. Phenotypically aberrant T-cell subsets detected by flow cytometry on whole blood from patients enrolled in the MHE100185 trial

Phenotypically aberrant T-cell populations are shown within a closed shape (circle, box) on dot plots, or are delimited by a horizontal bar (M1) on histograms. a: CD3-CD4+ cells (plot gated on total lymphocytes according to FSC/SSC), b: CD3-CD4+CD7- cells (histogram gated on CD3+CD4+ lymphocytes), c: CD3+CD4-(CD8+)CD5lo/- (plot gated on CD3+CD4- lymphocytes, which are mainly CD8+); d: CD3-CD4+CD8dim (plot gated on CD3+ lymphocytes); e: CD3-CD4dimCD8+ (plot gated on CD3+ lymphocytes); f. CD3+CD4+CD25hi (histogram gated on CD3+CD4+ lymphocytes)

Figure 2. Superiority of mepolizumab over placebo in patients with L-HES

The response rate of patients with L-HES to mepolizumab versus placebo is shown; white bars represent the mepolizumab treatment arm, and hatched bars represent the placebo treatment arm. PDN: prednisone. * p-values