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

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.

Key words: CD3^-CD4⁺, lymphocytic variant HES, clonal T-cell, TARC, IL-5, mepolizumab

Abbreviations used: AITL, Angioimmunoblastic T-cell lymphoma, APC, Allophycocyanin, FITC, Fluorescein isothiocyanate, F/P, FIP1-like 1/platelet-derived growth factor receptor α fusion, HES, Hypereosinophilic syndrome, L-HES, Lymphocytic variant hypereosinophilic syndrome, PE, Phycoerythrin, PerCP, Peridinin chlorophyll protein complex, TARC, Thymus-and-activation-regulated chemokine, TCR, T-cell receptor, TRG, T-cell receptor γ