Long term clinical outcomes of HES subjects treated with mepolizumab (anti-IL5)

Authors

• FL Kuang
• MP Fay
• JA Ware
• P Khoury
• AD Klion

Abstract

Rationale: Hypereosinophilic syndromes (HES) are defined by an absolute eosinophil count (AEC) >1500 cells/mm3 with evidence of end organ damage. Conventional therapies have variable efficacy and significant toxicity. The anti-IL-5 antibody, mepolizumab, has been shown to be safe and effective as a steroid-sparing agent in HES. The utility of mepolizumab in treating treatment-refractory HES is unknown. Methods: Part A: Treatment responses were examined in all subjects who received mepolizumab on an ongoing multicenter compassionate use protocol for treatment-refractory HES. Part B: Retrospective chart review of 261 subjects with PDGFRA-negative HES followed for > 5 years (or deceased within 5 years of the initial visit) on a protocol to study eosinophilia was performed. Clinical characteristics, events and responses to therapy were compared between subjects treated with conventional therapy (CONTROL; n=55) and those who responded to mepolizumab (MEPO; n=23). Results: Part A: Complete response (resolution of clinical symptoms and eosinophilia) was observed in 57% of the 35 treatment-refractory subjects who received mepolizumab. Peak AEC and HES clinical subtype appeared to be predictors of response. Part B: MEPO subjects had tried more therapies and had a longer duration of HES prior to initiation of therapy, suggesting that they were a more treatment refractory group. Nevertheless, overall mortality and malignancy incidence were similar to CONTROL. MEPO subjects were able to discontinue other HES therapies and maintain disease control over the long-term. Conclusions: These data suggest that mepolizumab is a viable therapeutic option for PDGFRA-negative HES subjects with refractory disease.

Scientific Focus Area: Immunology

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