Clinical efficacy and molecular biomarkers in a phase II study of tucidinostat plus R-CHOP in elderly patients with newl
- PDF / 2,181,306 Bytes
- 11 Pages / 595.276 x 790.866 pts Page_size
- 22 Downloads / 204 Views
Open Access
RESEARCH
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 Mu‑Chen Zhang1†, Ying Fang1†, Li Wang1,2†, Shu Cheng1, Di Fu1, Yang He1, Yan Zhao1, Chao‑Fu Wang3, Xu‑Feng Jiang4, Qi Song5, Peng‑Peng Xu1* and Wei‑Li Zhao1,2*
Abstract 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 Prog‑ nostic 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 phe‑ notype (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 pheno‑ type and molecular biomarkers on CR-CHOP response warrants further investigation in DLBCL. Trial registration ClinicalTrial.gov, NCT02753647. Registered on April 28, 2016. Keywords: Diffuse large B-cell lymphoma, Double expressor lymphoma, Histone deacetylase inhibitor, Tucidinostat, CREBBP/EP300
*Correspondence: [email protected]; [email protected] † Mu-Chen Zhang, Ying Fang and Li Wang have contributed equally to this manuscript. 1 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 Full list of author information is available at the end of the article
Background Diffuse large B-cell lymphoma (DLBCL) represents the most common subtype of non-Hodgkin’s lymphoma and is heterogeneous in clinical, immunophenotypic, and molecular features. More than 50% of DLBCL are elderly patients older than 60 years at diagnosis [1] and have advanced stage disease, intermediate- to high-risk International Prognostic Index (IPI) and adverse clinical outcome [2–4]. The progression-free survival (PFS) and overall survival (OS) rates were only 54% and 58% at
© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long a
Data Loading...
