Graf Solomon A, Gopal Ajay K
a Department of Medicine, University of Washington, Seattle , WA , USA.
b Fred Hutchinson Cancer Research Center , Seattle , WA , USA.
Expert Opin Pharmacother. 2016;17(2):265-74. doi: 10.1517/14656566.2016.1135130. Epub 2016 Jan 28.
B-cell Non-Hodgkin lymphomas (B-NHLs) include a number of disease subtypes, each defined by the tempo of disease progression and the identity of the cancerous cell. Idelalisib is a potent, selective inhibitor of the delta isoform of phosphatidylinositol-3-kinase (PI3K), a lipid kinase whose over-activity in B-NHL drives disease progression. Idelalisib has demonstrated activity in indolent B-NHL (iB-NHL) and is approved for use as monotherapy in patients with follicular lymphoma and small lymphocytic lymphoma and in combination with rituximab in patients with chronic lymphocytic leukemia.
Herein we review the development and pharmacology of idelalisib, its safety and efficacy in clinical studies of iB-NHL, and its potential for inclusion in future applications in iB-NHL and in combination with other therapies.
Idelalisib adds to the growing arsenal of iB-NHL pharmacotherapeutics and to the progression of the field toward precision agents with good efficacy and reduced toxicities. Nevertheless, idelalisib carries important risks that require careful patient counseling and monitoring. The appropriate sequencing of idelalisib with other proven treatment options in addition to its potential for combination with established or novel drugs will be borne out in ongoing and planned investigations.
B细胞非霍奇金淋巴瘤(B-NHL)包括多种疾病亚型,每种亚型由疾病进展速度和癌细胞特征定义。idelalisib是一种强效、选择性磷脂酰肌醇-3激酶(PI3K)δ亚型抑制剂,PI3K是一种脂质激酶,其在B-NHL中的过度活性会推动疾病进展。idelalisib已在惰性B-NHL(iB-NHL)中显示出活性,并被批准用于滤泡性淋巴瘤和小淋巴细胞淋巴瘤患者的单药治疗,以及用于慢性淋巴细胞白血病患者与利妥昔单抗联合治疗。
在此,我们综述idelalisib的研发和药理学、其在iB-NHL临床研究中的安全性和疗效,以及其在iB-NHL未来应用和与其他疗法联合应用中的潜力。
idelalisib增加了iB-NHL药物治疗的日益丰富的武器库,并推动该领域朝着具有良好疗效和降低毒性的精准药物发展。然而,idelalisib存在重要风险,需要对患者进行仔细的咨询和监测。idelalisib与其他已证实的治疗选择的适当序贯,以及其与已确立或新型药物联合应用的潜力,将在正在进行和计划中的研究中得到验证。