Clinical efficacy and tumour microenvironment influence of decitabine plus R‐CHOP in patients with newly diagnosed diffuse large B‐Cell lymphoma: Phase 1/2 and biomarker study

作者：Mu‐Chen Zhang, Ying Fang, Pengpeng Xu, Lei Dong, Rong Shen, Yao‐Hui Huang, Di Fu, Zi‐Xun Yan, Shu Cheng, Xufeng Jiang, Qi Song, Yang He, Yan Zhao, Min Lü, Jing Ye, Feng Liu, Lin Cheng, Chao‐Fu Wang, Li Wang, Weili Zhao · 发表于：Clinical and Translational Medicine · 年份：2021 · DOI：10.1002/ctm2.584 · 被引用次数：24 · 研究领域：Lymphoma Diagnosis and Treatment、CAR-T cell therapy research、Acute Lymphoblastic Leukemia research

Epigenetic gene alterations play an important role on diffuse large B cell lymphoma (DLBCL) progression.1 DNA methyltransferase inhibitor (DNMTi) decitabine has demonstrated anti-lymphoma activities, but never been applied for newly diagnosed DLBCL treatment. Here, we conducted for the first time a phase 1/2 trial of decitabine plus standard immunochemotherapy rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (DR-CHOP, NCT02951728) in DLBCL patients with international prognostic index (IPI) ≥ 2. The study determined the maximum tolerated dose (MTD) of decitabine as 10 mg/m2 on days 1–5 prior to R-CHOP on days 6–11 and showed promising efficacy and good tolerability. The trial enrolled 54 patients, 11 in phase 1 and 43 in phase 2 (Table 1). Among 49 evaluable patients (including six patients received the MTD of decitabine in phase 1), 39 (79.6%) patients achieved complete remission, and six (12.2%) patients achieved partial remission. Two-year progression-free survival (PFS), event-free survival (EFS) and overall survival (OS) rates were 71.4%, 65.3% and 87.8%, respectively (Figure 1A). Intermediate-high (IPI 2–3) or high-risk (IPI 4–5) patients presented similar outcomes (Figure 1B), irrespective on cell of origin and BCL2/MYC double expression (as defined by immunohistochemistry BCL2 ≥ 50% and MYC ≥ 40%) (Figure S1A,B). In our previous cohort of NHL-001 (NCT01852435), 2-year PFS was 59.6%, with OS as 76.2% for IPI ≥ 2 patients with standard R-CHOP (R-CHOP5...