From the Guidelines
Mastocytosis diagnosis and management should be guided by the most recent NCCN guidelines, which emphasize a multidisciplinary approach and consideration of the latest therapeutic options, as outlined in the 2024 guidelines 1.
Diagnostic Criteria
The diagnostic criteria for mastocytosis include the presence of multifocal dense infiltrates of mast cells in bone marrow or other extracutaneous organs, detection of the KIT D816V mutation, abnormal morphology of mast cells, aberrant expression of CD25 on mast cells, and elevated serum tryptase levels (typically >20 ng/mL) 1.
Management Options
Management of mastocytosis focuses on symptom control and depends on disease classification (cutaneous vs. systemic) and severity. First-line treatments include:
- H1 antihistamines (cetirizine 10mg daily or fexofenadine 180mg daily) to control pruritus and flushing
- H2 blockers (ranitidine 150mg twice daily or famotidine 20mg twice daily) for gastrointestinal symptoms
- Mast cell stabilizers like cromolyn sodium (200mg four times daily) for abdominal pain and diarrhea Patients should carry epinephrine auto-injectors for anaphylactic reactions. For advanced systemic mastocytosis, targeted therapies such as midostaurin (100mg twice daily) or avapritinib may be used, as recommended in the latest guidelines 1.
Additional Considerations
Corticosteroids can help with severe symptoms, while cytoreductive therapies like interferon-alpha or cladribine are reserved for aggressive disease. Patients should avoid known triggers such as alcohol, extreme temperatures, certain medications, and physical stimuli that can provoke mast cell degranulation. Regular monitoring of disease progression through serum tryptase levels and bone marrow examinations is essential for optimal management, with updates to the guidelines emphasizing the importance of a multidisciplinary approach and consideration of the latest therapeutic options 1.
From the FDA Drug Label
The efficacy of RYDAPT for MCL was based on the CR results by modified 2013 International Working Group-Myeloproliferative Neoplasms Research and Treatment-European Competence Network on Mastocytosis (IWG-MRT-ECNM) consensus criteria. Response after 6 cycles of RYDAPT was determined using a computational algorithm. Table 7 shows responses to RYDAPT according to modified Valent criteria Confirmed major or partial responses occurred in 46 of 73 patients with a documented KIT D816V mutation, 7 of 16 with wild-type or unknown status with respect to KIT D816V mutation, and 21 of 32 having prior therapy for SM
The diagnostic criteria for mastocytosis are not explicitly stated in the provided drug label. However, the label mentions the modified Valent criteria and IWG-MRT-ECNM consensus criteria used to assess response to treatment.
- Management options for mastocytosis include treatment with midostaurin (RYDAPT) 100 mg orally twice daily in 28-day cycles until disease progression or intolerable toxicity 2.
- The label also reports the efficacy of RYDAPT in Systemic Mastocytosis per modified Valent criteria and IWG-MRT-ECNM consensus criteria.
- Patients with KIT D816V mutation and those with prior therapy for SM are mentioned as subgroups in the study.
From the Research
Diagnostic Criteria for Mastocytosis
- The diagnosis of mastocytosis is based on the presence of multifocal clusters of spindled mast cells in the bone marrow, elevated serum tryptase level, abnormal mast cell CD25 expression, and presence of KITD816V mutation 3.
- Bone marrow tryptase level can be used as a diagnostic criterion for adult systemic mastocytosis, with a cut-off value of 50 μg/L identifying systemic mastocytosis with a sensitivity of 93.0% and a specificity of 90.0% 4.
- In skin biopsies, a sheet-like or subepidermal distribution of mast cells, a mast cell percentage above 40%, and a mast cell count per mm² can be used as diagnostic criteria for mastocytosis 5.
Management Options for Mastocytosis
- Treatment goals for indolent/smoldering systemic mastocytosis (ISM/SSM) patients are primarily directed towards anaphylaxis prevention, symptom control, and osteoporosis treatment 3.
- Patients with advanced systemic mastocytosis frequently need mast cell cytoreductive therapy to ameliorate disease-related organ dysfunction, with options including small-molecule inhibitors that target mutant-KIT, such as midostaurin or avapritinib 3.
- Other options for mast cell cytoreduction include cladribine or interferon-α, although head-to-head comparisons are lacking 3.
- Treatment of systemic mastocytosis with associated hematological neoplasm (SM-AHN) primarily targets the AHN component, particularly if an aggressive disease such as acute myeloid leukemia is present 3.
- Allogeneic stem cell transplant can be considered in patients with relapsed/refractory advanced systemic mastocytosis or in those with SM-AHN 3.
- Skin-directed therapy and novel systemic treatment options, including selective tyrosine kinase inhibitors, can be considered for patients with mastocytosis in the skin 6.