What Are Treatments For Systemic Mastocytosis?

Systemic mastocytosis is a rare disorder characterized by an excessive accumulation of mast cells (a type of white blood cell) in various body organs, including the skin, bone marrow, liver, spleen, and gastrointestinal tract. This can lead to a variety of symptoms, such as skin lesions, abdominal pain, diarrhea, and anaphylaxis. 

The treatment of systemic mastocytosis typically aims to control symptoms and prevent complications. The choice of treatment depends on the severity of the disease, the organs involved, and the patient's overall health status. 

The main treatment options for systemic mastocytosis include medications to control symptoms, chemotherapy, and stem cell transplantation.

What are symptom management options for systemic mastocytosis? 

The first line of treatment for systemic mastocytosis often involves medications to control symptoms. 

• Antihistamines, such as cetirizine and loratadine, help manage skin symptoms like flushing and itching, as well as gastrointestinal issues like stomach pain, heartburn, cramping, and diarrhea.
• Mast cell stabilizers, such as cromolyn sodium, prevent mast cells from releasing harmful substances, helping with allergy-like symptoms like rash, itching, and eye inflammation. 
• Antileukotriene drugs may be an option in patients with flushing, itching, or cramping who do not respond to antihistamines.
• Injectable epinephrine is sometimes needed if patients experience a full-body allergic reaction called anaphylaxis. 
• Monoclonal antibodies such as omalizumab (anti-IgE) can reduce the frequency of anaphylaxis. 
• Tyrosine kinase inhibitors (TKI inhibitors) such as midostaurin (Rydapt), avapritinib (Ayvakit), imatinib mesylate (Gleevec) are used like a directed therapy because they act by blocking enzymes that control the mast cell functions and growth. 
• Steroids such as prednisone reduce inflammation and have been used to control gastrointestinal issues like malabsorption, fluid build-up in the abdomen, stomach pain, bone pain, and skin disease that doesn’t respond to topical treatment. Steroids can also be used to prevent anaphylaxis.
• Proton pump inhibitors, such as omeprazole, help with stomach pain and other gastrointestinal symptoms. 
• Calcium and Vitamin D prevent bone weakness (osteoporosis) and fractures. 

Is chemotherapy used to treat systemic mastocytosis? 

Chemotherapy can reduce the number of mast cells in the body, helping to control symptoms and prevent complications. These drugs work by interfering with the growth of mast cells, thereby reducing their numbers. One chemotherapy drug commonly used is Cladribine (Leustatin).

What treatments are given to specific systemic mastocytosis subtypes? 

• Indolent systemic mastocytosis or smoldering systemic mastocytosis: The goal of treatment is to reduce the chances of full-body allergic reactions. However, if the disease doesn’t respond to common mediators like antihistamines, mast cell stabilizers, or other first-line drugs, the next step is to reduce mast cell numbers.  
• Aggressive systemic mastocytosis: Treatment is indicated to reduce the possibility of organ damage and improve the quality of life. For those patients eligible for stem cell transplant, the goal is to control symptoms and prevent progression until a donor can be found. The management of aggressive forms of systemic mastocytosis is with cladribine, midostaurin, interferon-alpha, or TKI inhibitors (imatinib) based on cytogenetics. along with a bone marrow transplant can also be an option. 
• Systemic mastocytosis with associated hematologic neoplasm: Treatment in this subtype focuses on the associated bone marrow or blood disorder. After initial therapy, a stem cell transplant should be considered for maintenance. 
• Mast cell leukemia: Although there is no standard treatment for mast cell leukemia, clinical trial participation is imperative for these patients. 
• Cladribine is a purine analog that shows activity across all subtypes of systemic mastocytosis. The National Comprehensive Cancer Network (NCCN) recommends cladribine for patients with systemic mastocytosis associated with blood or bone marrow cancer needing rapid mast cell reduction. It’s an effective treatment after other therapies like interferon-alpha or midostaurin.

Is stem cell transplantation an option for systemic mastocytosis? 

For patients with life-threatening systemic mastocytosis, allogeneic stem cell transplantation may be considered. This involves replacing the patient's diseased bone marrow (which produces mast cells) with healthy bone marrow from a donor. This can potentially cure the disease, but it carries significant risks, including infection, graft-versus-host disease, and even death. Therefore, it is usually reserved for the most severe cases.

What are some investigational drugs that are being tested in systemic mastocytosis patients? 

Clinical trials are not just a last resort for treating systemic mastocytosis. They can actually provide access to cutting-edge treatments that are not yet approved but show promise over years of testing. The choice of a clinical trial depends on a variety of factors including the patient's age, overall health, the subtype of the disease, and genetic changes in the leukemia cells. It's important to discuss all treatment options, including goals and possible side effects, with your healthcare team to help make the best decision. 

• Ripretinib is a type II switch control kinase inhibitor that has shown anti-tumor activity. A phase II study is ongoing to evaluate its effectiveness in advanced systemic mastocytosis.
• Interferon-alfa may benefit patients with smoldering systemic mastocytosis or slowly progressing aggressive systemic mastocytosis. However, it is still being studied and is not recommended for patients with indolent disease due to inconsistent response rates.
• Thalidomide has been studied in advanced systemic mastocytosis, though detailed outcomes and indications are less clear.
• Ruxolitinib is a JAK inhibitor, and has shown improvements in symptom burden and spleen size, helping improve patient’s quality of life

To learn more about your systemic mastocytosis clinical trial options, visit HealthTree's Systemic Mastocytosis Clinical Trial Finder. Utilize the advanced filter option to locate trials that you are eligible to participate in. You can create a HealthTree account to favorite your top trial options to discuss them with your systemic mastocytosis specialist.
 

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Source: 

• Systemic Mastocytosis Treatment & Management
• Systemic Mastocytosis