Pan-phosphatidylinositol 3-kinase inhibition with buparlisib in patients with relapsed or refractory non-Hodgkin lymphoma
Pan-phosphatidylinositol 3-kinase inhibition with buparlisib in patients with relapsed or refractory non-Hodgkin lymphoma
复制标题
布帕利西对复发或难治性非霍奇金淋巴瘤患者的泛磷脂酰肌醇 3 激酶抑制作用
作者：
A. Younes;G. Salles;G. Martinelli;R. Bociek;D. C. Barrigón;E. G. Barca;M. Turgut;J. Gerecitano;O. Kong;C. B. Pisal;R. Tavorath;W. Kim
磷脂酰肌醇3-激酶/雷帕霉素途径的机械性靶点的激活在非霍奇金淋巴瘤的发病机制中起着重要作用。这项多中心、开放标签的2期研究评估了丁帕利西布(BKM120)，一种泛I类磷脂酰肌醇3-激酶抑制剂，用于复发或难治性非霍奇金淋巴瘤患者。三组不同的患者(弥漫性大B细胞淋巴瘤、套细胞淋巴瘤或滤泡性淋巴瘤)每天接受一次布帕利西布100 mg，直到病情进展、不耐受或撤回同意。主要终点是基于队列6个月最佳总体反应的总体应答率；次要终点包括无进展生存期、反应持续时间、总生存期、安全性和耐受性。总共治疗了72例患者(26例弥漫性大B细胞淋巴瘤，22例套细胞淋巴瘤，24例滤泡性淋巴瘤)。弥漫性大B细胞淋巴瘤、套细胞淋巴瘤和滤泡性淋巴瘤的总有效率分别为11.5%、22.7%和25.0%，2例患者(弥漫性大B细胞淋巴瘤和套细胞淋巴瘤各1例)达到完全缓解。在进行安全性研究的人群中，最常见的(20%)不良反应是高血糖、疲劳和恶心(各占36.1%)、抑郁(29.2%)、腹泻(27.8%)和焦虑(25.0%)。最常见的3/4级不良反应包括高血糖(11.1%)和中性粒细胞减少(5.6%)。Buparlisib在复发或难治性非霍奇金淋巴瘤中显示出活性，部分患者病情稳定，肿瘤负担持续减轻，毒性可接受。有必要开发以机制为基础的联合方案和布帕利西。(这项研究由诺华制药公司资助，在ClinicalTrials.gov编号NCT01693614注册)。
Activation of the phosphatidylinositol 3-kinase/mechanistic target of rapamycin pathway plays a role in the pathogenesis of non-Hodgkin lymphoma. This multicenter, open-label phase 2 study evaluated buparlisib (BKM120), a pan-class I phosphatidylinositol 3-kinase inhibitor, in patients with relapsed or refractory non-Hodgkin lymphoma. Three separate cohorts of patients (with diffuse large B-cell lymphoma, mantle cell lymphoma, or follicular lymphoma) received buparlisib 100 mg once daily until progression, intolerance, or withdrawal of consent. The primary endpoint was overall response rate based on a 6-month best overall response by cohort; secondary endpoints included progression-free survival, duration of response, overall survival, safety, and tolerability. Overall, 72 patients (26 with diffuse large B-cell lymphoma, 22 with mantle cell lymphoma, and 24 with follicular lymphoma) were treated. The overall response rates were 11.5%, 22.7%, and 25.0% in patients with diffuse large B-cell lymphoma, mantle cell lymphoma, and follicular lymphoma, respectively; two patients (one each with diffuse large B-cell lymphoma and mantle cell lymphoma) achieved a complete response. The most frequently reported (>20%) adverse events of any grade in the population in which safety was studied were hyperglycemia, fatigue, and nausea (36.1% each), depression (29.2%), diarrhea (27.8%), and anxiety (25.0%). The most common grade 3/4 adverse events included hyperglycemia (11.1%) and neutropenia (5.6%). Buparlisib showed activity in relapsed or refractory non-Hodgkin lymphoma, with disease stabilization and sustained tumor burden reduction in some patients, and acceptable toxicity. Development of mechanism-based combination regimens with buparlisib is warranted. (This study was funded by Novartis Pharmaceuticals Corporation and registered with ClinicalTrials.gov number, NCT01693614).
影响因子：
45.3
作者：
Mayer, Ingrid A.;Abramson, Vandana G.;Arteaga, Carlos L.
通讯作者：
Arteaga, Carlos L.
影响因子：
20.3
作者：
Rudelius, Martina;Pittaluga, Stefania;Raffeld, Mark
通讯作者：
Raffeld, Mark