What is the treatment for systemic mastocytosis?

Treatment of Systemic Mastocytosis

The treatment of systemic mastocytosis should be based on disease classification (indolent, smoldering, or advanced forms) with all patients requiring anti-mediator drugs to control symptoms, while advanced forms may need additional cytoreductive therapies such as midostaurin, cladribine, or other targeted agents. 1

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 1
• Essential safety measures include:
  • Carrying two epinephrine auto-injectors at all times 1
  • Counseling about avoiding triggers of mast cell activation (temperature extremes, anxiety, stress) 1
  • Premedication before procedures, surgery, or contrast imaging 1

Treatment for Indolent and Smoldering Systemic Mastocytosis

• First-line treatment focuses on controlling mast cell activation symptoms with anti-mediator drugs: 1, 2

  • H1 antihistamines (for pruritus, flushing, tachycardia)
  • H2 antihistamines (for gastrointestinal symptoms)
  • Oral cromolyn sodium (for gastrointestinal symptoms)
  • Leukotriene receptor antagonists (for respiratory symptoms)
  • Aspirin (for flushing, though may trigger activation in some patients)
  • Omalizumab (for refractory symptoms)

• Regular monitoring is essential: 1

  • History, physical exam, and labs every 6-12 months
  • DEXA scan every 1-3 years for patients with bone density issues
  • Assessment of symptom burden using validated tools (MSAF and MQLQ)
  • Restaging if symptoms worsen

Treatment for Advanced Systemic Mastocytosis

Advanced forms require cytoreductive therapies in addition to symptom management: 1, 3, 4

• Midostaurin (FDA and EMA approved) is the preferred first-line therapy for advanced systemic mastocytosis 1, 3
• Cladribine should be considered when rapid debulking of disease is required 1, 5
• Imatinib is only recommended if KIT D816V mutation is negative/unknown or if eosinophilia is present with FIP1L1-PDGFRA fusion gene 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
• Allogeneic hematopoietic stem cell transplantation may be considered in eligible patients with aggressive disease 4

Treatment Algorithm

1. Determine disease classification (indolent, smoldering, or advanced)

2. For all patients:

   • Implement anti-mediator therapy based on symptoms
   • Educate about trigger avoidance and emergency management
   • Ensure regular follow-up

3. For advanced disease, add cytoreductive therapy:

   • First-line: Midostaurin
   • For rapid debulking: Cladribine
   • For KIT D816V negative cases: Imatinib
   • For slowly progressive disease: Interferons

Common Pitfalls and Caveats

• Aspirin can help with certain symptoms but may trigger mast cell activation in some patients - use with caution 1
• Treatment response is highly individual - a stepwise approach is often necessary 2
• Conventional anti-KIT D816V kinase inhibitors have shown limited success in many patients 5
• Additional genetic mutations (TET2, SRSF2, ASXL1, RUNX1, JAK2, RAS) may be present in advanced disease and can impact prognosis and treatment response 4
• Novel targeted therapies are emerging and may be considered for severely affected, therapy-refractory patients 2, 3