Standard medications remain the foundation of treatment for non-advanced systemic mastocytosis (SM). But for patients whose symptoms resist usual care, newer therapies that go beyond symptom control may offer relief. A new review published in ImmunoTargets and Therapy explores the landscape of these novel therapies.
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Much of the progress centers on KIT, a gene altered in most SM cases that pushes mast cells to grow and survive abnormally. Avapritinib, a highly selective tyrosine kinase inhibitorTyrosine kinase inhibitor Targeted therapies designed to block the KIT D816V mutation that drives most cases of SM. Includes avapritinib, midostaurin and imatinib. specifically designed to target and block the KIT D816V mutation, was approved for indolent SMIndolent SM A subtype of nonadvanced SM caused by the abnormal accumulation of mast cells in the bone marrow and other organs. Indolent SM accounts for around 90% of SM cases. after a trial showed it reduced both symptoms and mast cellMast cell A type of white blood cell produced in the bone marrow. They help defend against infections and play a key role in allergic reactions. In SM, mast cells become overactive and build up throughout the body. burden.
Two related drugs, bezuclastinib and elenestinib, remain in testing but have produced strong early drops in disease markers.
Another approach aims to calm mast cells rather than destroy them. Omalizumab, an antibody already used for allergies and asthma, has reduced anaphylaxisAnaphylaxis A severe allergic reaction that can turn fatal without treatment. Patients with SM are at a higher risk of developing anaphylaxis. and other symptoms in some patients.
The review also surveyed a broader pipeline of experimental options, from the biologic dupilumab and targeted drugs such as masitinib to antibodies designed to quiet specific mast-cell receptors, though most are early in development and have not yet been studied in SM.
Alongside the foundational treatments and the emerging therapies, the review notes that regular follow-up remains a cornerstone of good care, keeping symptoms in check and watching for signs of progression.
Significant questions still remain: no reliable test yet distinguishes symptoms caused by overactive mast cells from those caused simply by having too many of them, long-term safety data are limited and the best doses for the newest drugs are not yet clear.
“Continued progress will depend on integrating mechanistic insights with clinically meaningful endpoints to enable more precise, durable, and individualized treatment strategies for patients with non-advanced SMAdvanced SM In these subtypes of SM, mast cells begin to damage organs. Advanced SM includes the subtypes aggressive SM, mast cell leukemia and SM with an associated hematological neoplasm.,” the researchers concluded.
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