Midostaurin resulted in durable responses in patients with advanced systemic mastocytosis (SM) independent of the dosage amount, according to a study recently published in the British Journal of Haematology.
Midostaurin is a 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., a type of therapy that targets the KIT gene to reduce the number of mast cells in the body. Previous studies have established that midostaurin results in a favorable clinical response among a significant population of patients with 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., which includes the subtypes aggressive SMAggressive SM A subtype of advanced SM marked by a high mast cell burden that leads to organ damage. Aggressive SM accounts for less than 10% of SM cases., SM with an associated hematological neoplasmSM with an associated hematological neoplasm A form of advanced SM and the second-most common subtype of SM overall. In this subtype, SM occurs alongside another blood disorder. Also called SM with an associated myeloid neoplasm. and mast cell leukemiaMast cell leukemia The most severe subtype of SM, caused by the rapid buildup of immature mast cells in the bone marrow and blood. Mast cell leukemia accounts for less than 5% of SM cases and has a poor prognosis..
A team of researchers in Germany sought to better clarify how different doses of midostaurin affected outcomes among patients with advanced SM. They identified 79 patients with advanced SM who were treated with midostaurin at a German hospital between 2009 and 2021. They then carefully assessed their clinical response to midostaurin therapy and monitored any reported side effects.
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The starting doses of midostaurin were 100 mg daily (63 patients), 150 mg daily (two patients) or 200 mg daily (14 patients). Importantly, the research team found that responses as measured via serum tryptaseTryptase A protein enzyme that is primarily produced by mast cells and stored in small pockets within the cells, known as granules. High levels of tryptase are a key indicator of SM. levels, bone marrow 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. infiltration and KIT D816V expressed allele burden were independent of the midostaurin dose. This means that doctors have more room to adjust doses based on how well a patient tolerates the medication.
Overall, side effects and other unwanted responses led to dose modifications in just under half of patients. Researchers noted that these responses occurred in all subtypes of advanced SM and in all dosing regimens. Nausea was the most common side effect. Notably, they found that three patients had pyoderma gangrenosum as an adverse event, which is an inflammatory skin condition commonly associated with painful ulcers.
Among 41 patients who had assessable data, seven experienced midostaurin discontinuation syndrome, which is a rapid clinical deterioration after discontinuing midostaurin therapy. Five of the seven patients required hospitalization for their symptoms. The researchers found that gradually tapering the midostaurin dose and using corticosteroids were effective in preventing discontinuation syndrome in subsequent patients.
“In conclusion, midostaurin demonstrated a favourable safety profile and yielded durable responses in [advanced systemic mastocytosisMastocytosis Rare disease caused by the buildup of mast cells. Cutaneous mastocytosis primarily affects the skin and is more common in children, while systemic mastocytosis affects internal organs and is more common in adults.] patients across dosing regimens,” the study’s authors concluded.
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