DA-EPOCH-R combined with high-dose methotrexate in patients with newly diagnosed stage II-IV CD5-positive diffuse large B-cell lymphoma: a single-arm, open-label, phase II study

Haematologica. 2020 Sep 1;105(9):2308-2315. doi: 10.3324/haematol.2019.231076.


CD5-positive diffuse large B-cell lymphoma (CD5+ DLBCL) is characterized by poor prognosis and a high frequency of central nervous system relapse after standard immunochemotherapy. We conducted a phase II study to investigate the efficacy and safety of dose-adjusted (DA)- EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) combined with high-dose methotrexate (HD-MTX) in newly diagnosed patients with CD5+ DLBCL. Previously untreated patients with stage II to IV CD5+ DLBCL according to the 2008 World Health Organization classification were eligible. Four cycles of DA-EPOCH-R followed by two cycles of HD-MTX and four additional cycles of DAEPOCH- R (DA-EPOCH-R/HD-MTX) were planned as the protocol treatment. The primary end point was 2-year progression-free survival (PFS). Between September 25, 2012, and November 11, 2015, we enrolled 47 evaluable patients. Forty-five (96%) patients completed the protocol treatment. There were no deviations or violations in the DA-EPOCH-R dose levels. The complete response rate was 91%, and the overall response rate was 94%. At a median follow up of 3.1 years (range, 2.0-4.9 years), the 2- year PFS was 79% [95% confidence interval (CI): 64-88]. The 2-year overall survival was 89% (95%CI: 76-95). Toxicity included grade 4 neutropenia in 46 (98%) patients, grade 4 thrombocytopenia 12 (26%) patients, and febrile neutropenia in 31 (66%) patients. No treatment-related death was noted during the study. DA-EPOCH-R/HD-MTX might be a first-line therapy option for stage II-IV CD5+ DLBCL and warrants further investigation. (Trial registered at: UMIN-CTR: UMIN000008507.).

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Cyclophosphamide / therapeutic use
  • Doxorubicin / adverse effects
  • Etoposide / therapeutic use
  • Humans
  • Lymphoma, Large B-Cell, Diffuse* / diagnosis
  • Lymphoma, Large B-Cell, Diffuse* / drug therapy
  • Methotrexate* / therapeutic use
  • Neoplasm Recurrence, Local
  • Prednisone / adverse effects
  • Rituximab / therapeutic use
  • Vincristine / adverse effects


  • Rituximab
  • Vincristine
  • Etoposide
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone
  • Methotrexate

Supplementary concepts

  • EPOCH protocol

Associated data

  • UMIN-CTR/UMIN000008507

Grant support

Funding: This study was supported by grants-in-aid from the Japan Agency for Medical Research and Development, AMED (the Practical Research for Innovative Cancer Control; JP15Ack0106157, JP16ck0106157, JP17ck0106157, JP18ck0106439), the Ministry of Labour, Health, and Welfare of Japan (201438142A), the director of Mie University Hospital (2012, 2013), and the National Cancer Center Research and Development Fund (26-A-4, 29-A-3).