Though there have been significant advances in the diagnosis and treatment of indolent systemic mastocytosis (SM) in recent years, more research is still necessary, according to a new review published in the journal Annals of Hematology.
“A better understanding of ISM, its diagnosis, and the incorporation of biomarkers into management is essential for clinicians to identify ISM earlier, provide more targeted symptomatic relief, and address potential disease progression,” said the authors.
People with SM — a chronic blood disorder where immune cells called mast cells build up in the body — often have symptoms across multiple areas of the body. These may include skin issues like redness and itchiness, allergic reactions that cause trouble breathing, as well as weak and brittle bones (osteoporosis).
Many patients manage well with treatments that block the chemicals released by mast cells, like antihistamines and leukotriene blockers. For those with tough-to-treat symptoms, newer therapies like avapritinib (which blocks the faulty KIT gene that is usually the root of the disease) have shown clear benefit. Other potential treatments, like bezuclastinib, elenestinib and TL-895, are also being studied.
What is a KIT gene mutation?
SM is usually caused by a sporadic mutation in the KIT gene, which codes for a protein called CD117 transmembrane tyrosine kinase. The protein is involved in the growth, survival and migration of mast cells. The most common KIT mutation associated with SM is the D816V mutation, which results in the amino acid aspartic acid being replaced by the amino acid valine in the protein chain.
“Despite unquestionable benefits to patients, there are several important questions that remain in the current treatment landscape of indolent SM,” the researchers said.
Experts don’t yet know the best long-term dose or schedule for avapritinib or other KIT inhibitors or whether these drugs can eventually be stopped safely. It’s also unclear whether targeting the KIT gene early could slow disease progression, whether KIT inhibitors are safe in the long-term and whether it should replace traditional symptom-based treatments.
Read more about SM treatment and care
Even the tests that doctors use to guide treatment decisions require more research. Blood tests like tryptase, often used to monitor the disease, don’t always match how patients feel.
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