在一项新诊断的弥漫性大 B 细胞淋巴瘤老年患者中使用曲昔替丁加 R-CHOP 的 II 期研究中的临床疗效和分子生物标志物。

Clinical efficacy and molecular biomarkers in a phase II study of tucidinostat plus R-CHOP in elderly patients with newly diagnosed diffuse large B-cell lymphoma.

机构信息

Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine At Shanghai, Ruijin Hospital Affiliated To Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Pôle de Recherches Sino-Français en Science du Vivant Et Génomique, Laboratory of Molecular Pathology, Shanghai, China.

出版信息

Clin Epigenetics. 2020 Oct 23;12(1):160. doi: 10.1186/s13148-020-00948-9.

BACKGROUND

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).

RESULTS

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.

CONCLUSION

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.

背景

老年弥漫性大 B 细胞淋巴瘤（DLBCL）患者临床结局较差，不能耐受强化化疗。组蛋白去乙酰化酶抑制剂（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 他西地尼（以前称为西达本胺）联合 R-CHOP（CR-CHOP）治疗新诊断的弥漫性大 B 细胞淋巴瘤（国际预后指数≥2）老年患者的疗效和安全性。

结果

在 49 例患者中，完全缓解率为 86%，总缓解率为 94%。2 年无进展生存（PFS）和总生存（OS）率分别为 68%（95%CI 52-79）和 83%（95%CI 68-91）。与历史对照（NCT01852435）相比，双表达淋巴瘤表型（DEL）的 2 年 PFS 和 OS 率得到改善，CR-CHOP 也减轻了组蛋白乙酰转移酶 CREBBP/EP300 突变的不良预后影响。283 个周期中，171 例发生 3-4 级中性粒细胞减少，27 例发生 3-4 级血小板减少，11 例发生 3 级贫血。未报告 4 级非血液学不良事件。