Hypereosinophilic syndrome response to mepolizumab in the setting of a compassionate use program.

Mepolizumab, an anti-interleukin-5 antibody, has been proven a safe and effective glucocorticoid (GC)-sparing drug for many patients with nonclonal hypereosinophilic syndrome (HES) and is now approved in many countries. It remains unclear, however, which patients are most likely to benefit from therapy and whether the currently approved dosing regimen is appropriate for all. This observational retrospective study included all patients with HES who were enrolled in the MHE104317 compassionate use program (CUP) in our center. Patient and disease characteristics, mepolizumab dosing, and both clinical and hematological responses to treatment were collected from medical files. Treatment responses and mepolizumab dosing requirements were analyzed according to disease characteristics. Eighteen patients with HES were enrolled in the CUP, of whom nine are still on treatment. The median duration of exposure to mepolizumab was 45 mo (maximum 18 yr). A lower number of affected organs, requirement for GC dosing ≤10 mg prednisone-equivalent, and single-organ HES were associated with a higher likelihood of complete response. Lymphocytic variant HES (L-HES) was less treatment-responsive, leading to withdrawal and/or requiring higher mepolizumab dosing to achieve some degree of disease control. In contrast, all patients with single-organ disease had a complete response that could often be maintained despite increasing between-dose intervals. Few potentially treatment-related adverse events were observed despite prolonged exposure. This study confirms the efficacy and safety of mepolizumab in HES, although patients with L-HES rarely experience a complete response. In contrast, patients with single-organ disease affecting the lungs are often super-responders, and decreasing mepolizumab dosing may be attempted.