Page 130 - 2020_09-Haematologica-web

Ferrata Storti Foundation
Haematologica 2020 Volume 105(9):2308-2315
Non-Hodgkin Lymphoma
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
Kana Miyazaki,1 Naoko Asano,2 Tomomi Yamada,3 Kohta Miyawaki,4 Rika Sakai,5 Tadahiko Igarashi,6 Momoko Nishikori,7 Kinya Ohata,8 Kazutaka Sunami,9 Isao Yoshida,10 Go Yamamoto,11 Naoki Takahashi,12
13 14 15 15 Masataka Okamoto, Hiroki Yano, Yuki Nishimura, Satoshi Tamaru,
Masakatsu Nishikawa,15 Koji Izutsu,11,16 Tomohiro Kinoshita,17
Junji Suzumiya,18 Koichi Ohshima,19 Koji Kato,4 Naoyuki Katayama1 and Motoko Yamaguchi1
1Department of Hematology and Oncology, Mie University Graduate School of Medicine, Mie; 2Department of Molecular Diagnostics, Nagano Prefectural Shinshu Medical Center, Suzaka; 3Department of Medical Innovation, Osaka University Hospital, Suita; 4Department of Medicine and Biosystemic Science, Kyushu University Graduate School
of Medical Sciences, Fukuoka; 5Department of Medical Oncology, Kanagawa Cancer Center, Yokohama; 6Hematology/Oncology Division, Gunma Cancer Center, Ohta; 7Department of Hematology and Oncology, Kyoto University Graduate School of Medicine, Kyoto; 8Department of Hematology, Kanazawa University, Kanazawa; 9Department of Hematology, National Hospital Organization Okayama Medical Center, Okayama; 10Department of Hematologic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama; 11Department of Hematology, Toranomon Hospital, Tokyo; 12Department of Hematology and Oncology, International Medical Center, Saitama
Medical University, Hidaka; 13Department of Hematology, Fujita Health University School
of Medicine, Toyoake; 14Department of Hematology, Kainan Hospital Aichi Prefectural Welfare Federation of Agricultural Cooperatives, Yatomi; 15Clinical Research Support Center, Mie University Hospital, Tsu; 16Department of Hematology, National Cancer Center Hospital, Tokyo; 17Department of Hematology and Cell Therapy, Aichi Cancer Center Hospital, Nagoya; 18Department of Oncology and Hematology, Shimane University Hospital, Izumo and 19Department of Pathology, Kurume University School of Medicine, Kurume, Japan
ABSTRACT
CD5-positive diffuse large B-cell lymphoma (CD5+ DLBCL) is charac- terized 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, doxoru- bicin, and rituximab) combined with high-dose methotrexate (HD-MTX) in newlydiagnosedpatientswithCD5+ DLBCL.Previouslyuntreatedpatients with stage II to IV CD5+ DLBCL according to the 2008 World Health Organization classification were eligible. Four cycles of DA-EPOCH-R fol- lowed by two cycles of HD-MTX and four additional cycles of DA- EPOCH-R (DA-EPOCH-R/HD-MTX) were planned as the protocol treat- ment. 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 treat- ment. 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.)
Correspondence:
KANA MIYAZAKI
kmiyazaki@clin.medic.mie-u.ac.jp
Received: July 11, 2019. Accepted: October 21, 2019. Pre-published: October 24, 2019.
doi:10.3324/haematol.2019.231076 ©2020 Ferrata Storti Foundation
Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or inter- nal use. Sharing published material for non-commercial pur- poses is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for com- mercial purposes is not allowed without permission in writing from the publisher.
2308
haematologica | 2020; 105(9)
ARTICLE