What is the treatment for mastocytosis?

From the Guidelines

Treatment for mastocytosis should be guided by the most recent NCCN guidelines, which recommend a multidisciplinary team approach and referral to specialized centers with expertise in mastocytosis, as outlined in the 2024 NCCN Guidelines Insights: Systemic Mastocytosis, version 3.2024 1. The treatment plan typically involves a combination of medications to manage symptoms, including H1 antihistamines like cetirizine (10mg daily) or fexofenadine (180mg daily), H2 blockers such as ranitidine (150mg twice daily) or famotidine (20mg twice daily), and mast cell stabilizers like cromolyn sodium (200mg four times daily) to prevent mast cell degranulation. Some key points to consider in the treatment of mastocytosis include:

• The use of epinephrine auto-injectors for patients at risk of anaphylaxis, as recommended by the NCCN guidelines 1
• Avoidance of known triggers such as alcohol, certain medications, extreme temperatures, and physical stress, as suggested by the 2019 international overview and consensus recommendations on the management of suspected immediate perioperative allergic reactions 1
• Regular monitoring by specialists to adjust treatment plans based on symptom control and disease progression, as emphasized in the 2024 NCCN Guidelines Insights: Systemic Mastocytosis, version 3.2024 1
• Consideration of cytoreductive therapy for patients with advanced systemic mastocytosis, as recommended by the NCCN guidelines 1
• The importance of a multidisciplinary team approach, involving dermatologists, hematologists, pathologists, gastroenterologists, allergists, and immunologists, as outlined in the 2024 NCCN Guidelines Insights: Systemic Mastocytosis, version 3.2024 1.

From the FDA Drug Label

1. 2 Systemic Mastocytosis RYDAPT is indicated for the treatment of adult patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), or mast cell leukemia (MCL).
2. 3 Recommended Dosage in ASM, SM-AHN, and MCL The recommended dose of RYDAPT for patients with ASM, SM-AHN, and MCL is 100 mg orally twice daily with food. Continue treatment until disease progression or unacceptable toxicity occurs.

The treatment for mastocytosis is midostaurin (RYDAPT) at a dose of 100 mg orally twice daily with food. Treatment should be continued until disease progression or unacceptable toxicity occurs 2.

• The dose may need to be modified based on toxicity, with specific guidelines provided for ANC less than 1 x 10^9/L, platelet count less than 50 x 10^9/L, and hemoglobin less than 8 g/dL.
• Patients should be monitored for toxicity at least weekly for the first 4 weeks, every other week for the next 8 weeks, and monthly thereafter while on treatment.

From the Research

Treatment for Mastocytosis

The treatment for mastocytosis varies depending on the subtype and severity of the disease.

• For indolent/smoldering systemic mastocytosis (ISM/SSM), treatment is generally limited to anaphylaxis prevention, symptom control, and osteoporosis treatment 3, 4.
• For advanced systemic mastocytosis, including aggressive SM (ASM), SM with associated hematological neoplasm (SM-AHN), and mast cell leukemia (MCL), treatment often involves mast cell (MC) cytoreductive therapy to ameliorate disease-related organ dysfunction 3, 4.
• High response rates have been seen with small-molecule inhibitors that target mutant-KIT, including midostaurin (Food and Drug Administration approved) or avapritinib (investigational) 3, 4.
• Other options for MC cytoreduction include cladribine or interferon-α, although head-to-head comparisons are lacking 3, 4.
• Treatment of SM-AHN primarily targets the AHN component, particularly if an aggressive disease such as acute myeloid leukemia is present 3, 4.
• Allogeneic stem cell transplant can be considered in patients with SM-AHN or those with relapsed/refractory advanced SM 3, 4.
• Imatinib has a limited therapeutic role in SM, with effective cytoreduction limited to those with imatinib-sensitive KIT mutations 3, 4, 5.

Management of Symptoms

Symptoms of mast cell activation can be managed by:

• Blockade of mediator receptors (H1 and H2 antihistamines, leukotriene receptor blockade) 6.
• Inhibition of mediator synthesis (aspirin, zileuton) 6.
• Mediator release (sodium cromolyn) 6.
• Anti-IgE therapy, or a combination of these approaches 6.
• Acute episodes of mast cell activation require epinephrine, and prolonged episodes may be addressed with corticosteroids 6.

Novel Treatment Options

Novel systemic treatment options, including selective tyrosine kinase inhibitors, can be considered for patients with mastocytosis, with the potential to improve patient outcomes 7.