What are the treatment options for systemic mastocytosis (Systemic Mast Cell Activation Disorder)?

From the Guidelines

Treatment for systemic mastocytosis should prioritize avapritinib (200mg daily) as the first-line cytoreductive therapy for advanced or aggressive disease, given its superior overall survival benefit compared to midostaurin and cladribine, as demonstrated in the most recent study 1.

Overview of Systemic Mastocytosis Treatment

Systemic mastocytosis is a complex condition that requires a tailored treatment approach based on disease severity and symptoms. The primary goal of treatment is to alleviate symptoms, prevent organ damage, and improve quality of life.

First-Line Therapies

For most patients, first-line therapy includes:

• H1 antihistamines like cetirizine (10mg daily) or fexofenadine (180mg daily)
• H2 blockers such as famotidine (20mg twice daily) to control skin symptoms and gastrointestinal issues
• Cromolyn sodium (200mg four times daily) to stabilize mast cells and reduce GI symptoms

Advanced or Aggressive Disease

For advanced or aggressive systemic mastocytosis, cytoreductive therapies like:

• Avapritinib (200mg daily) is recommended as the first-line treatment due to its superior overall survival benefit 1
• Midostaurin (100mg twice daily) and cladribine chemotherapy cycles may be considered as alternative options

Additional Considerations

• Patients should carry epinephrine auto-injectors and know how to use them in case of anaphylactic reactions
• Bone health should be monitored, and bisphosphonates may be necessary to prevent osteoporosis
• Patients should avoid known mast cell triggers, including certain medications (NSAIDs, opioids), alcohol, extreme temperatures, and physical stress
• Regular follow-up with hematology specialists is essential to monitor disease progression and adjust treatment as needed

Key Takeaways

• Avapritinib is the preferred first-line cytoreductive therapy for advanced or aggressive systemic mastocytosis due to its superior overall survival benefit 1
• A tailored treatment approach is necessary to manage symptoms and prevent organ damage
• Regular monitoring and follow-up with hematology specialists are crucial to optimize treatment outcomes.

From the FDA Drug Label

One open-label, multicenter, Phase 2 study was conducted testing imatinib mesylate in diverse populations of patients with life-threatening diseases associated with Abl, Kit or PDGFR protein tyrosine kinases. This study included 5 patients with ASM treated with 100 mg to 400 mg of imatinib mesylate (imatinib as free base) daily

In addition to these 5 patients, 10 published case reports and case series describe the use of imatinib mesylate in 23 additional patients with ASM aged 26 to 85 years who also received 100 mg to 400 mg of imatinib mesylate (imatinib as free base) daily

Of the 28 patients treated for ASM, 8 (29%) achieved a complete hematologic response and 9 (32%) a partial hematologic response (PHR) (61% overall response rate)

Imatinib mesylate has not been shown to be effective in patients with less aggressive forms of systemic mastocytosis (SM).

Imatinib mesylate is therefore not recommended for use in patients with cutaneous mastocytosis, indolent systemic mastocytosis (smoldering SM or isolated bone marrow mastocytosis), SM with an associated clonal hematological non-mast cell lineage disease, mast cell leukemia, mast cell sarcoma or extracutaneous mastocytoma

Patients that harbor the D816V mutation of c-Kit are not sensitive to imatinib mesylate and should not receive imatinib mesylate.

The treatment options for Aggressive Systemic Mastocytosis (ASM) include imatinib mesylate at a dose of 100 mg to 400 mg daily.

• Complete Hematologic Response: 29% of patients achieved a complete hematologic response.
• Partial Hematologic Response: 32% of patients achieved a partial hematologic response. However, imatinib mesylate is not recommended for patients with less aggressive forms of systemic mastocytosis or those with the D816V mutation of c-Kit 2.

From the Research

Treatment Options for Systemic Mastocytosis

The treatment options for systemic mastocytosis (Systemic Mast Cell Activation Disorder) can be categorized into several approaches:

• Symptomatic treatment: This includes the use of histamine antagonists, cromolyn sodium, corticosteroids, and leukotriene-receptor inhibitors to prevent mast cell mediators release 3.
• Cytoreductive treatment: This approach aims to reduce the burden of mast cells and includes the use of interferon, cladribine, and tyrosine kinase inhibitors 3, 4.
• Targeted therapies: Novel therapeutic options have emerged, including tyrosine kinase inhibitors directed at the KIT protein and targeted monoclonal antibodies, which decrease MC activation or reduce mast cell burden 5.
• KIT-targeting tyrosine kinase inhibitors: These are beneficial for patients with advanced systemic mastocytosis, particularly those with the KIT D816V mutation 4.

Specific Treatment Strategies

The treatment strategy for systemic mastocytosis depends on the variant and severity of the disease:

• Indolent systemic mastocytosis: Patients are usually treated symptomatically, but may require cytoreductive treatments in some cases 6, 4.
• Aggressive systemic mastocytosis: Patients require advanced therapies and may tolerate higher levels of adverse effects 5.
• Systemic mastocytosis with an associated clonal hematologic non-mast cell lineage disease: The prognosis and treatment outcome may vary depending on the presence of morphological features of myelodysplasia or monocytosis 6.

Emerging Therapies

Several new medications are under development, which are expected to revolutionize the treatment for patients with systemic mastocytosis:

• Novel tyrosine kinase inhibitors: These may offer improved treatment options for patients with advanced systemic mastocytosis 5, 4.
• Targeted monoclonal antibodies: These may provide a new approach to reducing mast cell burden and decreasing MC activation 5.