Avapritinib versus Placebo in Indolent Systemic Mastocytosis.
Рандомизированное исследованиеСтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Gotlib Jason, Castells Mariana, Elberink Hanneke Oude, Siebenhaar Frank, Hartmann Karin, Broesby-Olsen Sigurd, George Tracy I, Panse Jens, Alvarez-Twose Iván, Radia Deepti H, Tashi Tsewang, Bulai Livideanu Cristina, Sabato Vito, Heaney Mark, Van Daele Paul, Cerquozzi Sonia, Dybedal Ingunn, Reiter Andreas, Pongdee Thanai, Barete Stéphane, Ustun Celalettin, Schwartz Lawrence, Ward Brant R, Schafhausen Philippe, Vadas Peter, Bose Prithviraj, DeAngelo Daniel J, Rein Lindsay, Vachhani Pankit, Triggiani Massimo, Bonadonna Patrizia, Rafferty Mark, Butt Nauman M, Oh Stephen T, Wortmann Friederike, Ungerstedt Johanna, Guilarte Mar, Taparia Minakshi, Kuykendall Andrew T, Arana Yi Cecilia, Ogbogu Princess, Gaudy-Marqueste Caroline, Mattsson Mattias, Shomali William, Giannetti Matthew P, Bidollari Ilda, Lin Hui-Min, Sulllivan Erin, Mar Brenton, Scherber Robyn, Roche Maria, Akin Cem, Maurer Marcus
Аннотация
BACKGROUND: Indolent systemic mastocytosis (ISM) is a clonal mast-cell disease driven by the KIT D816V mutation. We assessed the efficacy and safety of avapritinib versus placebo, both with best supportive care, in patients with ISM. METHODS: We randomized patients with moderate to severe ISM (total symptom score [TSS] of ≥28; scores range from 0 to 110, with higher numbers indicating more severe symptoms) two to one to avapritinib 25 mg once daily (n=141) or placebo (n=71). The primary end point was mean change in TSS based on the 14-day average of patient-reported severity of 11 symptoms. Secondary end points included reductions in serum tryptase and blood KIT D816V variant allele fraction (≥50%), reductions in TSS (≥50% and ≥30%), reduction in bone marrow mast cells (≥50%), and quality of life measures. RESULTS: From baseline to week 24, avapritinib-treated patients had a decrease of 15.6 points (95% CI, −18.6 to −12.6) in TSS compared to a decrease of 9.2 points (−13.1 to −5.2) in the placebo group; P<0.003. From baseline to Week 24, 76/141 patients (54%; 45% to 62%) in the avapritinib group compared to 0/71 patients in the placebo group achieved a ≥50% reduction in serum tryptase level; P<0.001. Edema and increases in alkaline phosphatase were more common with avapritinib than placebo; there were few treatment discontinuations because of adverse events. CONCLUSIONS: In this trial, avapritinib was superior to placebo in reducing uncontrolled symptoms and mast-cell burden in patients with ISM. The long-term safety and efficacy of this approach for patients with ISM remain the focus of the ongoing trial. (Funded by Blueprint Medicines Corporation; ClinicalTrials.gov number, NCT03731260.)