Treatment of Systemic Mastocytosis
The treatment of systemic mastocytosis should be tailored based on disease subtype, with indolent forms managed primarily with anti-mediator therapy while advanced forms require cytoreductive agents such as midostaurin, cladribine, or interferons. 1
Disease Classification and Initial Management
- Systemic mastocytosis (SM) is classified into indolent SM (ISM), smoldering SM (SSM), and advanced forms including aggressive SM (ASM), SM with associated hematologic neoplasm (SM-AHN), and mast cell leukemia (MCL) 1
- Referral to specialized centers with expertise in mastocytosis management is strongly recommended for all patients 1
- All patients should carry two epinephrine auto-injectors and be counseled about avoiding triggers of mast cell activation 1
- Multidisciplinary collaboration with subspecialists (e.g., anesthesia for procedures, high-risk obstetrics for pregnancy) is essential 1
Treatment for Indolent and Smoldering Systemic Mastocytosis
Anti-mediator Drug Therapy
- First-line treatment focuses on controlling mast cell activation symptoms with anti-mediator drugs 1:
- H1 antihistamines for pruritus, flushing, urticaria, and tachycardia
- H2 antihistamines for gastrointestinal symptoms
- Oral cromolyn sodium for diarrhea, abdominal pain, nausea, and vomiting
- Leukotriene receptor antagonists for refractory skin and gastrointestinal symptoms
- Aspirin for symptoms associated with elevated urinary prostaglandin levels (use with caution as it may trigger mast cell activation)
- Omalizumab for refractory symptoms
Monitoring
- Regular follow-up with history, physical exam, and labs every 6-12 months 1
- DEXA scan every 1-3 years for patients with osteopenia/osteoporosis 1
- Assessment of symptom burden using validated tools (MSAF and MQLQ) 1
Advanced Therapy for Refractory Cases
- For ISM or SSM with severe, refractory mediator symptoms or bone disease not responsive to anti-mediator therapy, consider:
Treatment for Advanced Systemic Mastocytosis
First-line Options
- Midostaurin - FDA and EMA approved for advanced SM 1, 3
- Cladribine - particularly useful when rapid debulking of disease is required 1
- Imatinib - only if KIT D816V mutation negative/unknown or if eosinophilia is present with FIP1L1-PDGFRA fusion gene 1
- Interferons (interferon alfa-2b, peginterferon alfa-2a, or peginterferon alfa-2b) ± prednisone - more suitable for slowly progressive disease 1
- Avapritinib - recently approved for advanced SM and also for indolent SM 3, 4
Treatment Selection Considerations
- For patients with ASM, choice between agents depends on:
SM with Associated Hematologic Neoplasm (SM-AHN)
- Initial assessment to determine whether SM component or AHN component requires more immediate treatment 1
- May require organ-directed biopsy to determine whether organ damage is related to SM or AHN 1
- Consider AHN-directed therapy including multiagent chemotherapy when appropriate 1
Mast Cell Leukemia (MCL)
- Most aggressive form requiring immediate intervention 1
- Consider clinical trials, cytoreductive therapy, and evaluation for allogeneic hematopoietic stem cell transplantation 1, 5
Emerging Therapies
- Novel KIT inhibitors in development: ripretinib, bezuclastinib, elenestinib, masitinib, nintedanib 3
- Other targeted approaches under investigation:
Common Pitfalls and Caveats
- Avoid triggering factors for mast cell activation (temperature extremes, anxiety, stress) 1
- Premedications are essential before procedures, surgery, or imaging with contrast 1
- Aspirin can help with certain symptoms but may trigger mast cell activation in some patients 1
- Presence of small lytic bone lesions alone is insufficient to diagnose advanced SM or initiate cytoreductive therapy 1
- In chronic MCL without organ damage, cytoreductive therapy should still be considered due to poor prognosis 1
- Regular monitoring for disease progression is essential, with restaging if symptoms worsen 1