使用分子谱分析对新诊断的滤泡性淋巴瘤 (FL) 进行可靠的预后和生物学分类仍然具有挑战性。使用 RNA 测序、DNA 测序、免疫组织化学 (IHC) 和/或荧光原位杂交对 RELEVANCE 试验中接受利妥昔单抗化疗 (R-chemo) 或利妥昔单抗-来那度胺 (R2) 治疗的患者的 FL 肿瘤进行分析。无监督基因聚类识别出两个分别富含正常记忆 (MEM) B 细胞和生发中心 (GC) B 细胞信号的基因表达特征 (GS)。这两个 GS 被组合成一个 20 基因预测因子 (FL20)，将患者分为 MEM 样 (n = 160) 或 GC 样 (n = 164) 亚型，这些亚型也显示出不同的突变谱。在 R 化疗组中，MEM 样患者的无进展生存期 (PFS) 显着短于 GC 样患者（HR=2.13；p=0.0023），并且这种预后相关性在包括 FLIPI 的多变量模型中仍然显着（p= 0.005）。在 R2 组中，两种亚型的 PFS 相当，表明对于 MEM 样患者，R2 优于 R 化疗（HR=0.54；p=0.011）。 FL20 的预后价值在采用 R 化疗的独立 FL 队列 (GSE119214 (n=137)) 中得到验证。使用 FOXP1、LMO2、CD22 和 MUM1 抗体开发了一种 IHC 算法 (FLCM)，该算法在 RELEVANCE (n=264) 患者训练组中与 FL20 具有显着的预后相关性，然后在另一组患者 (n=116) 中进行了验证）。这些数据表明，FL 肿瘤可分为 MEM 样和 GC 样亚型，它们在生物学上不同，临床风险状况也不同。 FLCM 检测可用于常规临床实践，以识别可能从 R 化疗以外的疗法（例如 R2 组合）中受益的 MEM 样 FL 患者。 ClinicalTrials.gov 标识符：相关：NCT01476787 和 NCT01650701 简介。版权所有 © 2024 美国血液学会。

A robust prognostic and biological classification for newly diagnosed follicular lymphoma (FL) using molecular profiling remains challenging. FL tumors from patients treated in the RELEVANCE trial with rituximab-chemotherapy (R-chemo) or rituximab-lenalidomide (R2) were analyzed using RNA-sequencing, DNA-sequencing, immunohistochemistry (IHC) and/or fluorescence in situ hybridization. Unsupervised gene clustering identified two gene expression signatures (GS) enriched with normal memory (MEM) B-cells and germinal center (GC) B-cells signals, respectively. These two GS were combined into a 20-genes predictor (FL20) to classify patients into MEM-like (n=160) or GC-like (n=164) subtypes, which also displayed different mutational profiles. In the R-chemo arm, MEM-like patients had significantly shorter progression free survival (PFS) than GC-like patients (HR=2.13; p=0.0023), and this prognostic correlation remained significant in a multivariable model including FLIPI (p=0.005). In the R2 arm, both subtypes had comparable PFS, demonstrating a R2 benefit over R-chemo for MEM-like patients (HR=0.54; p=0.011). The prognostic value of FL20 was validated in an independent FL cohort with R-chemo treatment (GSE119214 (n=137)). An IHC algorithm (FLCM) using FOXP1, LMO2, CD22 and MUM1 antibodies was developed with significant prognostic correlation with FL20 in a training set of RELEVANCE (n=264) patients, which was then validated in a different set of patients (n=116). These data indicate that FL tumors can be classified into MEM-like and GC-like subtypes that are biologically distinct and clinically different in risk profile. The FLCM assay can be used in routine clinical practice to identify MEM-like FL patients who might benefit from therapies other than R-chemo, such as the R2 combination. ClinicalTrials.gov identifier: RELEVANCE: NCT01476787 and NCT01650701 INTRODUCTION.Copyright © 2024 American Society of Hematology.