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.

Abstract

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.).

• Authors: Kana Miyazaki, Naoko Asano, Tomomi Yamada, Kohta Miyawaki, Rika Sakai, Tadahiko Igarashi, Momoko Nishikori, Kinya Ohata, Kazutaka Sunami, Isao Yoshida, Go Yamamoto, Naoki Takahashi, Masataka Okamoto, Hiroki Yano, Yuki Nishimura, Satoshi Tamaru, Masakatsu Nishikawa, Koji Izutsu, Tomohiro Kinoshita, Junji Suzumiya, Koichi Ohshima, Koji Kato, Naoyuki Katayama, Motoko Yamaguchi
• Journal: Haematologica (Haematologica) Vol. 105 Issue 9 Pg. 2308-2315 (09 01 2020) ISSN: 1592-8721 [Electronic] Italy
• PMID: 33054055 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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