Department of Hematology, Centre Henri Becquerel, Rouen, France.
INSERM U1245, Centre Henri Becquerel, University of Rouen, Rouen, France.
Blood Adv. 2023 Dec 12;7(23):7331-7345. doi: 10.1182/bloodadvances.2023011169.
Primary mediastinal B-cell lymphoma (PMBL) is an uncommon entity of aggressive B-cell lymphoma with an unusually good prognosis, except for 10-15% of chemotherapy-refractory cases. To identify earlier these higher risk patients, we performed molecular characterization of a retrospective multicenter cohort of patients treated with firstline immunochemotherapy. The traits of the patients with gene-expression profiling data (n = 120) were as follows: median age of 34 years (range, 18-67 years); female sex, 58.3%; elevated lactate dehydrogenase, 82.5%; Eastern Cooperative Oncology Group performance status score of 0 to 1, 85.7%; Ann Arbor stage I/II, 55%; International Prognostic Index score of 1 to 2, 64.4%; and median metabolic tumor volume, 290.4 cm3 (range, 15.7-1147.5 cm3). Among all 137 markers tested for correlation with survival data, only programmed death-ligand (PDL) 1 and PDL2 expression showed a prognostic impact. Overall, both PDL1 and PDL2 genes were highly expressed in 37 patients (30.8%; PDL1high/PDL2high). The baseline clinical characteristics of patients with PDL1high/PDL2high were similar to those of other patients. In univariate analysis, PDL1high/PDL2high status was associated with poor progression-free survival (PFS) (hazard ratio [HR], 4.292) and overall survival (OS; HR, 8.24). In multivariate analysis, PDL1high/PDL2high status was an independent prognostic factor of adverse outcomes (PFS: HR, 5.22; OS: HR, 10.368). We validated these results in an independent cohort of 40 patients and confirmed the significant association between PDL1high/PDL2high status and inferior PFS (HR, 6.11). High PDL1/PDL2 gene expression defines a population with strong immune privilege and poorer outcomes from standard chemotherapy who might benefit from firstline checkpoint inhibitor therapy.
原发性纵隔 B 细胞淋巴瘤（PMBL）是一种罕见的侵袭性 B 细胞淋巴瘤实体，预后异常良好，但约有 10-15%的化疗耐药病例除外。为了更早地识别这些高风险患者，我们对接受一线免疫化疗的回顾性多中心队列患者进行了分子特征分析。具有基因表达谱数据的患者（n=120）的特征如下：中位年龄 34 岁（范围，18-67 岁）；女性，58.3%；乳酸脱氢酶升高，82.5%；东部合作肿瘤组体能状态评分为 0-1，85.7%；Ann Arbor 分期 I/II，55%；国际预后指数评分为 1-2，64.4%；代谢肿瘤体积中位数为 290.4 cm3（范围，15.7-1147.5 cm3）。在所有 137 个与生存数据相关的标志物中进行测试，只有程序性死亡配体（PDL）1 和 PDL2 表达显示出预后影响。总体而言，37 例患者（30.8%；PDL1high/PDL2high）中均高度表达 PDL1 和 PDL2 基因。PDL1high/PDL2high 患者的基线临床特征与其他患者相似。在单因素分析中，PDL1high/PDL2high 状态与无进展生存期（PFS；危险比[HR]，4.292）和总生存期（OS；HR，8.24）不良相关。在多因素分析中，PDL1high/PDL2high 状态是不良结局的独立预后因素（PFS：HR，5.22；OS：HR，10.368）。我们在 40 例患者的独立队列中验证了这些结果，并证实了 PDL1high/PDL2high 状态与较差的 PFS 之间存在显著关联（HR，6.11）。高 PDL1/PDL2 基因表达定义了具有强大免疫特权和较差标准化疗结局的人群，他们可能受益于一线检查点抑制剂治疗。
