美国斯坦福大学Jason Gotlib等研究人员完成阿瓦普替尼对晚期系统性肥大细胞增多症(AdvSM)的疗效和安全性的2期临床试验。这一研究成果于2021年12月6日在线发表在国际学术期刊《自然—医学》上。
Title: Efficacy and safety of avapritinib in advanced systemic mastocytosis: interim analysis of the phase 2 PATHFINDER trial
Author: Gotlib, Jason, Reiter, Andreas, Radia, Deepti H., Deininger, Michael W., George, Tracy I., Panse, Jens, Vannucchi, Alessandro M., Platzbecker, Uwe, Alvarez-Twose, Ivn, Mital, Andrzej, Hermine, Olivier, Dybedal, Ingunn, Hexner, Elizabeth O., Hicks, Lisa K., Span, Lambert, Mesa, Ruben, Bose, Prithviraj, Pettit, Kristen M., Heaney, Mark L., Oh, Stephen T., Sen, Jayita, Lin, Hui-Min, Mar, Brenton G., DeAngelo, Daniel J.
Issue&Volume: 2021-12-06
Abstract: Advanced systemic mastocytosis (AdvSM) is a rare, KIT D816V-driven hematologic neoplasm characterized by mast cell infiltration and shortened survival. We report the results of a prespecified interim analysis of an ongoing pivotal single-arm phase2 trial (no. NCT03580655) of avapritinib, a potent, selective KIT D816V inhibitor administered primarily at a once-daily starting dose of 200mg in patients with AdvSM (n=62). The primary endpoint was overall response rate (ORR). Secondary endpoints included mean baseline change in AdvSM–Symptom Assessment Form Total Symptom Score and quality of life, time to response, duration of response, progression-free survival, overall survival, changes in measures of disease burden and safety. The primary endpoint was successfully met (P=1.6×10-9), with an ORR of 75% (95% confidence interval 57–89) in 32response-evaluable patients with AdvSM who had sufficient follow-up for response assessment, including 19% with complete remission with full or partial hematologic recovery. Reductions of ≥50% from baseline in serum tryptase (93%), bone marrow mast cells (88%) and KIT D816V variant allele fraction (60%) were observed. The most frequent grade≥3 adverse events were neutropenia (24%), thrombocytopenia (16%) and anemia (16%). Avapritinib demonstrated a high rate of clinical, morphological and molecular responses and was generally well tolerated in patients with AdvSM.
DOI: 10.1038/s41591-021-01539-8
Source: https://www.nature.com/articles/s41591-021-01539-8
Nature Medicine:《自然—医学》,创刊于1995年。隶属于施普林格·自然出版集团,最新IF:30.641
官方网址:https://www.nature.com/nm/
投稿链接:https://mts-nmed.nature.com/cgi-bin/main.plex