What are the treatment options for hypereosinophilia?

Treatment Options for Hypereosinophilia

The treatment of hypereosinophilia should be tailored to the specific subtype, with corticosteroids remaining the first-line therapy for most patients with idiopathic hypereosinophilic syndrome (HES), while targeted therapies like imatinib are recommended for specific genetic variants. 1, 2

Diagnostic Approach Before Treatment

• Before initiating treatment, it's essential to determine whether the hypereosinophilia is:

  • Secondary/reactive (non-hematologic causes)
  • Primary/clonal (hematologic disorders) 1

• Diagnostic evaluation should include:

  • Blood and bone marrow morphologic review
  • Standard cytogenetics
  • Fluorescence in situ hybridization
  • Molecular testing for tyrosine kinase gene fusions
  • Flow immunophenotyping 1

First-Line Treatment Options

Corticosteroids

• Corticosteroids remain the mainstay of treatment for idiopathic HES and lymphocyte-variant hypereosinophilia 1, 2
• Prednisone is typically started at 1-2 mg/kg for severe cases with small-caliber esophagus, weight loss, or requiring hospitalization 3
• For patients with eosinophilic esophagitis (EoE), topical swallowed corticosteroids are preferred over systemic steroids due to fewer adverse effects 3

Tyrosine Kinase Inhibitors

• Imatinib is the treatment of choice for patients with PDGFRA or PDGFRB rearrangements due to its exquisite effectiveness 1, 2
• For patients with hypereosinophilic syndrome with cardiac involvement, consider prophylactic systemic steroids (1-2 mg/kg) for 1-2 weeks concomitantly with imatinib at initiation of therapy 4

Second-Line and Alternative Treatments

Biologic Agents

• Mepolizumab (anti-IL-5 antibody) is FDA-approved for idiopathic HES and has demonstrated corticosteroid-sparing effects 5, 1
• Benralizumab (anti-IL-5 receptor antibody) has shown significant lowering of eosinophil counts in hypereosinophilic disorders, with 74% of patients having sustained response at 48 weeks 6
• These biologic agents should be considered for patients who are refractory to or intolerant of corticosteroids 1, 7

Cytotoxic Agents

• Hydroxyurea and interferon-alpha have demonstrated efficacy as initial treatment and in steroid-refractory cases of HES 1, 2
• For aggressive forms of HES and chronic eosinophilic leukemia (CEL), cytotoxic chemotherapy agents and hematopoietic stem cell transplantation may be necessary 1

Treatments Not Recommended

• Cromolyn sodium has no apparent therapeutic benefit for patients with eosinophilic disorders 3
• Leukotriene receptor antagonists might provide symptomatic relief at high dosages but have no demonstrable effect on eosinophilia 3
• Anti-TNF therapies have shown no benefit in eosinophilic disorders 3
• Immunosuppressive agents (azathioprine or 6-mercaptopurine) are not recommended due to insufficient evidence 3

Monitoring and Maintenance Therapy

• For milder forms of eosinophilia (<1.5 × 10^9/L) without symptoms or signs of organ involvement, a watch-and-wait approach with close follow-up may be appropriate 1, 7
• After achieving remission, maintenance therapy is often necessary as disease recurrence is common when treatment is discontinued 3
• For patients with eosinophilic esophagitis who respond to PPI treatment, maintenance PPI therapy can be considered as long-term treatment due to high risk of relapse on stopping therapy 3

Special Considerations

• For patients with cardiac involvement, perform echocardiogram and determine serum troponin before initiating treatment 4
• Monitor for potential adverse effects of treatments:
  • Corticosteroids: growth should be carefully monitored in children 3
  • Imatinib: monitor for cardiogenic shock/left ventricular dysfunction, especially in patients with hypereosinophilic syndrome with cardiac involvement 4
  • Topical steroids: monitor for esophageal candidiasis (occurs in up to 22% of patients) 3