伊布替尼
淋巴瘤
切碎
弥漫性大B细胞淋巴瘤
肿瘤科
内科学
医学
布鲁顿酪氨酸激酶
化疗
癌症研究
慢性淋巴细胞白血病
白血病
受体
酪氨酸激酶
作者
Wyndham H. Wilson,George E. Wright,Da-Wei Huang,Brendan Hodkinson,Sriram Balasubramanian,Yue Fan,Jessica Vermeulen,Martin Shreeve,Louis M. Staudt
出处
期刊:Cancer Cell
[Elsevier]
日期:2021-12-01
卷期号:39 (12): 1643-1653.e3
被引量:41
标识
DOI:10.1016/j.ccell.2021.10.006
摘要
In diffuse large B cell lymphoma (DLBCL), tumors belonging to the ABC but not GCB gene expression subgroup rely upon chronic active B cell receptor signaling for viability, a dependency that is targetable by ibrutinib. A phase III trial ("Phoenix;" ClinicalTrials.gov: NCT01855750) showed a survival benefit of ibrutinib addition to R-CHOP chemotherapy in younger patients with non-GCB DLBCL, but the molecular basis for this benefit was unclear. Analysis of biopsies from Phoenix trial patients revealed three previously characterized genetic subtypes of DLBCL: MCD, BN2, and N1. The 3-year event-free survival of younger patients (age ≤60 years) treated with ibrutinib plus R-CHOP was 100% in the MCD and N1 subtypes while the survival of patients with these subtypes treated with R-CHOP alone was significantly inferior (42.9% and 50%, respectively). This work provides a mechanistic understanding of the benefit of ibrutinib addition to chemotherapy, supporting its use in younger patients with non-GCB DLBCL.
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