CEOP/IVE/GDP alternating regimen compared with CEOP as the first-line therapy for newly diagnosed patients with peripheral T cell lymphoma: results from a phase 2, multicenter, randomized, controlled clinical trial

Genome Medicine

Yu-Jie Jiang¹  Xin Wang¹  Xiao-Sheng Fang¹  Yong-Ping Song²  Li-Hua Dong²  Xiao-Yun Zheng³  Jian-Da Hu³  Wei-Li Zhao⁴  Ming-Ci Cai⁴  Shu Cheng⁴  Yao-Hui Huang⁴  Li Wang⁴  Zi-Xun Yan⁴  Peng-Peng Xu⁴  Meng-Meng Ji⁴ 

[1]Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University

[2]Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University, The First Affiliated Hospital of Zhengzhou University

[3]Fujian Institute of Hematology, Fujian Medical University Union Hospital

[4]State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine

关键词: Peripheral T cell lymphoma;    Alternating regimen;    CHOP;    Overall response rate;    Prognosis;    Prognostic biomarker;   

DOI  :  10.1186/s13073-020-00739-0

来源: DOAJ

【 摘 要 】

Abstract Background Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)/CHOP-like chemotherapy is widely used in peripheral T cell lymphoma (PTCL). Here we conducted a phase 2, multicenter, randomized, controlled trial, comparing the efficacy and safety of CEOP/IVE/GDP alternating regimen with CEOP in newly diagnosed PTCL. Methods PTCL patients, except for anaplastic large cell lymphoma-anaplastic lymphoma kinase positive, were 1:1 randomly assigned to receive CEOP/IVE/GDP (CEOP, cyclophosphamide 750 mg/m2, epirubicin 70 mg/m2, vincristine 1.4 mg/m2 [maximum 2 mg] on day 1, and prednisone 60 mg/m2 [maximum 100 mg] on days 1–5 every 21 days, at the first and fourth cycle; IVE, ifosfamide 2000 mg/m2 on days 1–3, epirubicin 70 mg/m2 on day 1, and etoposide 100 mg/m2 on days 1–3 every 21 days, at the second and fifth cycle; and GDP, gemcitabine 1000 mg/m2 on days 1 and 8, cisplatin 25 mg/m2 on days 1–3, and dexamethasone 40 mg on days 1–4 every 21 days, at the third and sixth cycle) and CEOP (every 21 days for 6 cycles). Analysis of efficacy and safety was of the intent-to-treatment population. The primary endpoint was a complete response rate at the end of treatment. Meanwhile, whole exome sequencing and targeted sequencing were performed in 62 patients with available tumor samples to explore prognostic biomarkers in this cohort as an exploratory post hoc analysis. Results Among 106 patients, 53 each were enrolled to CEOP/IVE/GDP and CEOP. With 51 evaluable patients each in two groups, a complete response rate of the CEOP/IVE/GDP group was similar to that of the CEOP group (37.3% vs. 31.4%, p = 0.532). There was no difference in median progression-free survival (PFS; 15.4 months vs. 9.2 months, p = 0.122) or overall survival (OS; 24.3 months vs. 21.9 months, p = 0.178). Grade 3–4 hematological and non-hematological adverse events were comparable. Histone modification genes were most frequently mutated (25/62, 40.3%), namely KMT2D, KMT2A, SETD2, EP300, and CREBBP. Multivariate analysis indicated that CREBBP and IDH2 mutations were independent factors predicting poor PFS and OS (all p < 0.001), while KMT2D predicting poor PFS (p = 0.002). Conclusions CEOP/IVE/GDP alternating regimen showed no remission or survival advantage to standard chemotherapy. Future clinical trials should aim to develop alternative regimen targeting disease biology as demonstrated by recurrent mutations in epigenetic factors. Trial registration The study was registered on ClinicalTrial.gov (NCT02533700) on August 27, 2015.

【 授权许可】

Unknown