Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Biometric Research Branch, Division of Cancer Diagnosis and Treatment, National Cancer Institute, National Institutes of Health, Bethesda, MD 20850, USA.
Cancer Cell. 2021 Dec 13;39(12):1643-1653.e3. doi: 10.1016/j.ccell.2021.10.006. Epub 2021 Nov 4.
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.
在弥漫性大 B 细胞淋巴瘤（DLBCL）中，属于 ABC 而非 GCB 基因表达亚组的肿瘤依赖于慢性活跃的 B 细胞受体信号来维持生存，这种依赖性可以被伊布替尼靶向。一项 III 期试验（“凤凰”；ClinicalTrials.gov：NCT01855750）表明，在非 GCB DLBCL 的年轻患者中，伊布替尼联合 R-CHOP 化疗可提高生存率，但这种获益的分子基础尚不清楚。对来自凤凰试验患者的活检样本的分析揭示了三种以前表征的 DLBCL 遗传亚型：MCD、BN2 和 N1。接受伊布替尼联合 R-CHOP 治疗的年轻患者（年龄≤60 岁）的 3 年无事件生存率在 MCD 和 N1 亚型中为 100%，而单独接受 R-CHOP 治疗的这些亚型患者的生存率明显较差（分别为 42.9%和 50%）。这项工作提供了对伊布替尼联合化疗获益的机制理解，支持其在非 GCB DLBCL 的年轻患者中的应用。
