Advanced Systemic Mastocytosis (AdvSM): Symptoms, Diagnosis & Treatment Options

Advanced Systemic Mastocytosis (AdvSM) is classified as a rare and aggressive type of clonal mast cell disorder. It involves the accumulation of abnormal mast cells in one or more extracutaneous organs, including the spleen, bone marrow, liver, and gastrointestinal tract. The condition often causes multi-organ dysfunction. AdvSM is categorized into three subtypes:

• Aggressive Systemic Mastocytosis (ASM)
• Systemic Mastocytosis with an Associated Hematologic Neoplasm (SM-AHN)
• Mast Cell Leukemia (MCL)

Mast Cells and the KIT Mutation:

Mast cells play an important role in allergic and inflammatory responses. In AdvSM, mutations—particularly KIT D816V, found in over 90% of patients—cause unchecked mast cell proliferation and activation, contributing to the disease’s severity.

Clinical Symptoms of AdvSM:

Symptoms vary based on the organs involved, but may include:

• Severe fatigue
• Weight loss
• Gastrointestinal issues (diarrhea, nausea, abdominal pain)
• Bone pain and fractures
• Liver or spleen enlargement
• Skin lesions (in some patients)
• Cytopenias (thrombocytopenia, anemia)

Because of its overlap with other hematologic disorders, diagnosis generally requires specialized tests.

Diagnosis: A Multi-Step Process

The accurate diagnosis of Advanced Systemic Mastocytosis (AdvSM) involves:

• Molecular testing for KIT mutations
• Bone marrow biopsy with immunohistochemical staining for mast cells
• Serum tryptase levels (>20 ng/mL often indicative)
• Organ imaging to detect infiltration or dysfunction

As per the WHO 2022 classification, AdvSM is regarded as a high-grade systemic mastocytosis, and the condition typically requires comprehensive evaluation.

Treatment Goals in Advanced Systemic Mastocytosis (AdvSM):

• The major focus of treatment in AdvSM is to manage disease progression, improve quality of life, and address organ involvement. Key goals include:
• Alleviating symptoms
  Reducing the mast cell burden
• Stabilizing or reversing organ damage
• Prolonging survival

Treatment options include:

• Interferon-alpha
• Antihistamines and corticosteroids
• Cytoreductive therapy (e.g., cladribine)
• Targeted therapies, such as avapritinib

Ayvakit (Avapritinib): A Targeted Therapy Option

Ayvakit (avapritinib) is a tyrosine kinase inhibitor developed specifically to inhibit KIT D816V and other KIT alterations. It was approved by the U.S. FDA in June 2021 for the treatment of adults with AdvSM.
Indications:

• Aggressive Systemic Mastocytosis (ASM)
• Systemic Mastocytosis with Associated Hematologic Neoplasm (SM-AHN)
• Mast Cell Leukemia (MCL)

In the EXPLORER and PATHFINDER clinical trials, Ayvakit demonstrated:

• Significant reductions in mast cell burden
• Durable overall responses in patients with KIT D816V mutations
• Improved symptom scores in advanced disease cohorts

Safety Profile:
Common adverse effects include:

• edema
• diarrhea
• nausea
• fatigue/asthenia
  This therapeutic drug should only be used under the proper guidance of a hematologist-oncologist familiar with mast cell disorders.

Accessing Ayvakit in India:
AdvSM is a complex and life-threatening disease. It requires a timely diagnosis and a personalized treatment approach. With targeted therapies like Ayvakit, there is renewed hope for improving outcomes in affected patients.

Ayvakit is not yet available or approved in India. But, if you are looking to access Ayvakit in India or other global locations where it may not be commercially available or approved? You can legally request access via Named Patient Programs through trusted import partners like us.

Disclaimer: This article is intended for informational purposes only and should not replace medical advice. Patients should consult a qualified healthcare provider (HCP) for diagnosis and treatment decisions.

References:
U.S. Food & Drug Administration. FDA Approves Ayvakit (avapritinib) for Advanced Systemic Mastocytosis.
Avapritinib in advanced systemic mastocytosis: EXPLORER and PATHFINDER trials.