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 但不属于 GCB 基因表达亚组的肿瘤依赖于慢性活性 B 细胞受体信号转导来维持生存，这是依鲁替尼可靶向的依赖性。一项 III 期试验（“Phoenix”；“ClinicalTrials.gov：NCT01855750”）显示，在年轻的非 GCB DLBCL 患者中，依鲁替尼联合 R-CHOP 化疗具有生存获益，但这种获益的分子基础尚不清楚。对 Phoenix 试验患者的活组织检查分析揭示了三种先前表征的 DLBCL 遗传亚型：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%，而仅接受 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%）。