Treatment Options for Mastocytosis Diagnosed via Bone Biopsy
For patients with mastocytosis diagnosed via bone biopsy, treatment should be tailored to the specific subtype of disease, with midostaurin being the first-line therapy for aggressive systemic mastocytosis, while indolent forms are managed primarily with anti-mediator therapy. 1
Disease Classification and Initial Management
- Mastocytosis treatment depends on the World Health Organization (WHO) classification subtype, which includes indolent systemic mastocytosis (ISM), smoldering systemic mastocytosis (SSM), aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematologic neoplasm (SM-AHN), and mast cell leukemia (MCL) 1
- Referral to specialized centers with expertise in mastocytosis is strongly recommended for optimal management 1
- All patients should be counseled about signs/symptoms and potential triggers of mast cell activation, and should carry injectable epinephrine (2 auto-injectors) to manage potential anaphylaxis 1
Treatment for Indolent Systemic Mastocytosis (ISM) and Smoldering Systemic Mastocytosis (SSM)
- Management focuses primarily on controlling mast cell activation symptoms with anti-mediator drug therapy 1
- Regular monitoring includes H&P and labs every 6-12 months and DEXA scan every 1-3 years for patients with osteopenia/osteoporosis 1
- Clinical trials should be considered for patients with inadequate symptom control 1
- Cladribine and interferon-alfa may be considered in selected patients with severe, refractory mediator symptoms or bone disease not responsive to anti-mediator therapy or bisphosphonates 1
Treatment for Aggressive Systemic Mastocytosis (ASM)
First-line therapy options include: 1
- Midostaurin (100 mg orally twice daily with food) - FDA-approved for ASM, SM-AHN, and MCL 2
- 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 patients with slowly progressive disease 1
Allogeneic hematopoietic cell transplantation (HCT) should be considered in eligible patients with adequate response to therapy 1
Treatment for Systemic Mastocytosis with Associated Hematologic Neoplasm (SM-AHN)
- Treatment is primarily governed by the associated non-mast cell neoplasm 1, 3
- Midostaurin has shown efficacy in this population with a 16% overall response rate per modified IWG-MRT-ECNM consensus criteria 2
Treatment for Mast Cell Leukemia (MCL)
- Clinical trials are the preferred option 1
- Midostaurin, cladribine, or multiagent chemotherapy may be used 1
- Allogeneic HCT should be considered for eligible patients 1
Monitoring and Response Assessment
Re-staging should be performed with bone marrow aspirate and biopsy, serum tryptase level, and additional staging studies when there is: 1
- Return or progression of SM-related organ damage
- Symptomatic or progressive hepatomegaly or splenomegaly
- Progressive disease-related symptoms
- Intolerance to drug therapy
Response assessment should be based on improvement of disease-related symptoms and/or improvement of B-findings in ISM or SSM 1
Special Considerations for Bone Involvement
- DEXA scan should be performed to evaluate for osteopenia/osteoporosis 1
- Metastatic skeletal survey should be conducted to evaluate for osteolytic lesions 1
- Antiresorptive therapy with bisphosphonates or denosumab should be considered for patients with osteoporosis 4
- In advanced disease with high mast cell burden, mast-cell-derived mediators may promote osteoblastic activity, leading to osteosclerosis and apparent increases in bone mineral density 4
Diagnostic Pitfalls to Avoid
- Morphologically occult systemic mastocytosis in bone marrow can be missed without appropriate clinical suspicion and pathologic evaluation by tryptase and CD25 immunohistochemistry and KIT D816V mutation analysis 5
- Normal tryptase levels do not rule out myeloid neoplasms, as a minority of patients with systemic mastocytosis have normal tryptase levels 6, 7