美国国立卫生研究院Louis M. Staudt小组揭示依鲁替尼与R-CHOP化疗对DLBCL遗传亚型的影响。该研究于2021年11月4日在线发表于国际一流学术期刊《癌细胞》。

研究人员表示，在弥漫性大B细胞淋巴瘤（DLBCL）中，属于ABC而非GCB基因表达亚群的肿瘤依靠长期活跃的B细胞受体信号来维持生存，这种依赖性可被依鲁替尼靶向。一项III期试验（"Phoenix; "ClinicalTrials.gov: NCT01855750）显示，在年轻的非GCB DLBCL患者中，依鲁替尼加入R-CHOP化疗有生存优势，但这种优势的分子基础尚不清楚。

研究人员对Phoenix试验患者的活体组织分析显示，有三种先前定性的DLBCL基因亚型：MCD、BN2和N1。在MCD和N1亚型中，接受依鲁替尼加R-CHOP治疗的年轻患者（年龄≤60岁）的3年无事件生存率为100%，而单独接受R-CHOP治疗的这些亚型患者的生存率则明显较差（分别为42.9%和50%）。这项工作为依鲁替尼加入化疗的益处提供了机理上的理解，并支持其在年轻的非GCB DLBCL患者中使用。

附：英文原文

Title: Effect of ibrutinib with R-CHOP chemotherapy in genetic subtypes of DLBCL

Author: Wyndham H. Wilson, George W. Wright, Da Wei Huang, Brendan Hodkinson, Sriram Balasubramanian, Yue Fan, Jessica Vermeulen, Martin Shreeve, Louis M. Staudt

Issue&Volume: 2021-11-04

Abstract: In diffuse large B cell lymphoma (DLBCL), tumors belonging to the ABC but not GCBgene 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 youngerpatients with non-GCB DLBCL, but the molecular basis for this benefit was unclear.Analysis of biopsies from Phoenix trial patients revealed three previously characterizedgenetic subtypes of DLBCL: MCD, BN2, and N1. The 3-year event-free survival of youngerpatients (age ≤60 years) treated with ibrutinib plus R-CHOP was 100% in the MCD andN1 subtypes while the survival of patients with these subtypes treated with R-CHOPalone was significantly inferior (42.9% and 50%, respectively). This work providesa mechanistic understanding of the benefit of ibrutinib addition to chemotherapy,supporting its use in younger patients with non-GCB DLBCL.

DOI: 10.1016/j.ccell.2021.10.006

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(21)00557-2