-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

5060 Long-Term Follow-up of Hypereosinophilic Syndrome Patients Treated with Mepolizumab: A Nationwide Real-Life Study of 59 Patients

Program: Oral and Poster Abstracts
Session: 901. Health Services and Quality Improvement - Non-Malignant Conditions: Poster III
Hematology Disease Topics & Pathways:
adult, Clinical Practice (Health Services and Quality), Adverse Events, Study Population, Human
Monday, December 11, 2023, 6:00 PM-8:00 PM

Kevin Chevalier1*, Francois Barde2*, Alexandre Vallée3*, Lucile Grange4*, Gerard Socié5, Stanislas Faguer6*, Antoine Néel7*, Camille Taillé8*, Pascal Cathebras4*, Daniele Belgodere9*, Divi Cornec10*, Bernard Bonnotte, M.D, PhD11*, Guillaume Lefèvre12*, Matthieu Groh, MD, MSc13* and Jean-Emmanuel Kahn14*

1Internal Medicine, CHU Ambroise Paré, Le Kremlin-Bicêtre, AL, France
2Internal Medicine, CHU Ambroise Paré, Boulogne Billancourt, France
3Hôpital Foch, Suresnes, France
4CHU Saint Etienne, Saint Etienne, France
5Hopital St. Louis, Department of Hematology - BMT, Paris, France
6University Hospital of Rangueil, Toulouse, FRA
7CHU Hôtel-Dieu, Nantes, FRA
8CHU Bichat Claude Bernard, Paris, France
9CH Bastia, Bastia, France
10Brest University Hospital, Brest, FRA
11Faculty of Medicine - University Hospital of Dijon, Dijon, FRA
12Laboratoire d'Immunologie, CHU de Lille, Lille, France
13French National Reference Center for Hypereosinophilic Syndromes (CEREO), Departement of Internal Medicine, Hôpital Foch, Suresnes, France
14CHU Ambroise Paré, Boulogne Billancourt, FRA


Mepolizumab, a humanized monoclonal antibody directed against IL-5, has proven efficacious for the treatment of FIP1L1PDGFRA (F/P)-negative Hypereosinophilic Syndrome (HES) in two randomized controlled trials with short term follow-up. However, both its efficacy and safety profiles on the long term are unknown.


All F/P-negative HES patient treated with mepolizumab in France from 2003 to 2022 in either GlaxoSmithKline-sponsored randomized trials (MHE100185 and HES200622) or long-term access programs (MHE100901 and MHE10417) were included. For each study visit, we retrospectively collected the following data: drug doses (and spacing), HES-disease status, absolute eosinophil counts (AEC), and doses of oral corticosteroids (OCS). Clinical remission (CR) was defined as the absence of symptoms related to HES. Complete hematological remission (CHR) was defined as an AEC < 0.5 x 109/L, and relapse by the occurrence of new or worsening of HES-related symptoms, irrespective of either AEC or increase of HES treatments. Relapse-free survival was modeled using a Kaplan-Meier method. We also assessed the rates of “super responses”, a new outcome measure defined as the combination of both CR, CHR and complete withdrawal of OCS at last follow-up.

Results and discussion

Data were available for 64 out of the 80 patients identified. All patients ultimately received 300mg subcutaneous mepolizumab, but 27 (45.8%) patients had initially been started on higher doses (700 or 750 mg intravenous). Five patients were excluded because of misdiagnoses despite initially high AEC and HES-mimicking presentation (IgG4-related disease (n=1), Castleman’s disease (n=1), lymphoma (n=2) and STAT6 gain-of-function mutation (n=1)). Ultimately, the study population consisted of 59 patients (idiopathic HES, n=51; lymphocytic HES, n=8) with chronic HES sensitive to high-dose OCS yet who remained OCS-dependent on the long run (median [IQR] dose of OCS at baseline: 11 [9-20] mg/d). In median, patients had two organs involved, with gastro-intestinal, respiratory, and cutaneous manifestations being the most frequent symptoms.

After a median follow-up of 4.5 [2.5-12.3] years, 11 patients (19%) relapsed, among whom five were clearly related to prior mepolizumab spacing to more than four weeks between injections (Figure 1). In details, most of the patients were in CR (n=55, 93%) and/or in CHR (n=56, 95%) at last follow-up, including 38 (64%) OCS-free patients who fulfilled criteria for super response. No baseline predictive factor for super response was evidenced.

When focusing on the 21 (36%) patients with more than eight years of follow-up (median 14.4 [12.2-17.3] years), outcomes tended to be the same as those of the overall population. At last follow-up more than 70% of patients were able to space mepolizumab’s infusions for more than four weeks (median time between two injections at last follow-up: 8 [4-11] months). Ultimately, four patients were able to discontinue mepolizumab without subsequent relapse with more than two years of follow-up.

There was no new safety signal, and no patient withdrew mepolizumab due to a treatment-related adverse event.


Mepolizumab remains highly efficacious in the long-term (including in patients with more than 10 years of follow-up), enabling sustained disease remission despite tapering of OCS and spacing of injections. Very few cases of mepolizumab failure were identified, among which the leading cause was HES misdiagnosis.

Disclosures: Lefèvre: AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; GlaxoSmithKline: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Groh: GlaxoSmithKline: Consultancy, Honoraria; AstraZeneca: Consultancy. Kahn: GlaxoSmithKline: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees.

*signifies non-member of ASH