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 inhibitor, 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 SM, which includes the subtypes aggressive SM, SM with an associated hematological neoplasm and mast cell leukemia.
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 tryptase levels, bone marrow mast cell 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 mastocytosis] patients across dosing regimens,” the study’s authors concluded.
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