What is the treatment for systemic mastocytosis?

Treatment of Systemic Mastocytosis

The treatment of systemic mastocytosis should be tailored based on disease classification, with indolent and smoldering forms managed primarily with anti-mediator drugs, while advanced forms require targeted therapies like midostaurin or avapritinib. 1, 2

Disease Classification and Initial Management

• Systemic mastocytosis should be classified into indolent SM, smoldering SM, and advanced forms (aggressive SM, SM with associated hematologic neoplasm, and mast cell leukemia) to guide appropriate treatment 1
• All patients should be referred to specialized centers with expertise in mastocytosis management for optimal care 1
• Essential safety measures include prescribing two epinephrine auto-injectors and counseling about avoiding triggers of mast cell activation 1
• Multidisciplinary collaboration with subspecialists is crucial for comprehensive management 1

Treatment for Indolent and Smoldering Systemic Mastocytosis

• First-line treatment focuses on controlling mast cell activation symptoms with:

  • H1 antihistamines (for pruritus, flushing, tachycardia) 1, 3
  • H2 antihistamines (for gastrointestinal symptoms) 1, 3
  • Oral cromolyn sodium (for gastrointestinal symptoms) 1
  • Leukotriene receptor antagonists (for respiratory symptoms) 1
  • Aspirin (for flushing, after testing for tolerance) 1
  • Omalizumab (for refractory symptoms) 1

• Regular monitoring is essential:

  • Follow-up with history, physical exam, and labs every 6-12 months 1
  • DEXA scan every 1-3 years for patients with bone density concerns 1
  • Assessment of symptom burden using validated tools like MSAF and MQLQ 1

Treatment for Advanced Systemic Mastocytosis

• FDA-approved targeted therapies:

  • Midostaurin is FDA and EMA approved for all advanced systemic mastocytosis subtypes 1, 2
  • Avapritinib is now approved for advanced systemic mastocytosis and is the first cytoreductive agent approved for indolent systemic mastocytosis 2
  • Imatinib is recommended only if KIT D816V mutation is negative/unknown or if eosinophilia is present with FIP1L1-PDGFRA fusion gene 1, 2

• Additional treatment options:

  • Cladribine is particularly useful when rapid debulking of disease is required 1, 4
  • Interferons (interferon alfa-2b, peginterferon alfa-2a, or peginterferon alfa-2b), with or without prednisone, are more suitable for slowly progressive disease 1, 5

Common Pitfalls and Important Considerations

• Avoid triggering factors for mast cell activation:

  • Temperature extremes, anxiety, stress, alcohol, and certain medications 1
  • Premedications are essential before procedures, surgery, or imaging with contrast 1

• Medication cautions:

  • Aspirin can help with certain symptoms but may trigger mast cell activation in some patients - test tolerance in a controlled setting 1
  • Regular monitoring for disease progression is essential, with restaging if symptoms worsen 1

• Emerging therapies:

  • Newer KIT inhibitors (ripretinib, bezuclastinib, elenestinib, masitinib, nintedanib) are in clinical trials 2
  • Other investigational targets include Bruton's kinase (TL-895), interleukin-6 (sarilumab), and sialic acid-binding immunoglobulin-like lectin-8 (lirentelimab) 2

• Life expectancy in indolent systemic mastocytosis is generally not significantly different from the general population, but prognosis is worse in smoldering mastocytosis and advanced forms 4