Elderly patients with diffuse large B-cell lymphoma (DLBCL) present with poor clinical outcome and intolerance to intensive chemotherapy. Histone deacetylase inhibitors (HDACIs) show anti-lymphoma activities and can be applied to treat DLBCL. This study aimed to evaluate efficacy and safety of oral HDACI tucidinostat (formerly known as chidamide) plus R-CHOP (CR-CHOP) in elderly patients with newly diagnosed DLBCL (International Prognostic Index ≥ 2). Among 49 patients, the complete response rate was 86%, with overall response rate achieving 94%. The 2-year progression survival (PFS) and overall survival (OS) rates were 68% (95% CI 52–79) and 83% (95% CI 68–91). Comparing with historical control (NCT01852435), the 2-year PFS and OS rates of double-expressor lymphoma phenotype (DEL) were improved, and negative prognostic effect of histone acetyltransferases CREBBP/EP300 mutations was also mitigated by CR-CHOP. Grade 3–4 neutropenia was reported in 171, grade 3–4 thrombocytopenia in 27, and grade 3 anemia in 11 of 283 cycles. No grade 4 non-hematological adverse event was reported. CR-CHOP is effective and safe in elderly patients with newly diagnosed DLBCL. Relevance of DEL phenotype and molecular biomarkers on CR-CHOP response warrants further investigation in DLBCL. Trial registration ClinicalTrial.gov, NCT02753647. Registered on April 28, 2016.

中文翻译：

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tucidinostat 联合 R-CHOP 对新诊断的弥漫性大 B 细胞淋巴瘤老年患者的临床疗效和分子生物标志物


患有弥漫性大 B 细胞淋巴瘤 (DLBCL) 的老年患者临床效果不佳且对强化化疗不耐受。组蛋白脱乙酰酶抑制剂（HDACIs）具有抗淋巴瘤活性，可用于治疗 DLBCL。本研究旨在评估口服 HDACI tucidinostat（以前称为西达本胺）联合 R-CHOP (CR-CHOP) 对新诊断 DLBCL（国际预后指数≥ 2）的老年患者的疗效和安全性。 49名患者中，完全缓解率为86%，总体缓解率为94%。 2 年进展生存率 (PFS) 和总生存率 (OS) 分别为 68% (95% CI 52–79) 和 83% (95% CI 68–91)。与历史对照（NCT01852435）相比，CR-CHOP 改善了双表达淋巴瘤表型（DEL）的 2 年 PFS 和 OS 率，并且还减轻了组蛋白乙酰转移酶 CREBBP/EP300 突变的负面预后影响。在 283 个周期中，171 个周期报告了 3-4 级中性粒细胞减少症，27 个周期报告了 3-4 级血小板减少症，11 个周期报告了 3 级贫血。未报告 4 级非血液学不良事件。 CR-CHOP 对于新诊断的 DLBCL 老年患者有效且安全。 DEL 表型和分子生物标志物与 CR-CHOP 反应的相关性值得在 DLBCL 中进行进一步研究。试验注册 ClinicalTrial.gov，NCT02753647。注册日期：2016年4月28日。