Major progress has been made in the treatment of systemic mastocytosis (SM), but patients with the most aggressive forms of the disease still need more options, according to a recent review published in Mædica.
The biggest breakthrough is the use of tyrosine kinase inhibitors (TKIs), such as midostaurin and avapritinib. These medicines directly target the mutations of the KIT D816V gene, which drive the disease. “The targeted inhibition of mutated KIT kinase has offered unprecedented opportunities for improved disease control, symptomatic relief, and enhanced quality of life for patients,” the researchers said.
Supportive treatments remain important for managing the symptoms of SM. Antihistamines (such as H1 and H2 blockers) and mast cell stabilizers (like sodium cromolyn) help control flushing, itching and stomach upset. Epinephrine auto-injectors are essential for patients at risk of severe allergic reactions (anaphylaxis). Monoclonal antibodies like omalizumab are prescribed to some patients to control severe allergic symptoms, including recurrent anaphylaxis and hives (urticaria).
Bone health treatments, including bisphosphonates and calcium and vitamin D supplements, are recommended to prevent and treat osteoporosis and fractures, which are common in SM.
For more advanced, fast-spreading or treatment-resistant disease, stronger options exist. These include cladribine (a chemotherapy drug) and, in some cases, stem cell transplantation, which may cure the disease but carries significant risks.
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However, challenges remain. Some forms of SM — such as SM with another blood cancer (systemic mastocytosis with associated hematologic neoplasm, SM-AHN) or mast cell leukemia (MCL) — often do not respond well to current therapies. “These forms of SM continue to exhibit limited responsiveness to standard therapies, thereby underscoring an urgent need for novel treatment modalities,” the authors noted.
Looking ahead, researchers are testing next-generation TKIs (such as bezuclastinib and elenestinib) to learn how their effectiveness and side effects compare to current TKI drugs.
There is also growing interest in combination therapies, which use TKIs together with other targeted drugs, chemotherapy or immune-based treatments. This approach may be helpful when the disease stops responding to one medicine alone.
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