Randomized Phase III Trial of Ibrutinib and Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Non–Germinal Center B-Cell Diffuse Large B-Cell Lymphoma

Author:

Younes Anas1,Sehn Laurie H.2,Johnson Peter3,Zinzani Pier Luigi4,Hong Xiaonan5,Zhu Jun6,Patti Caterina7,Belada David89,Samoilova Olga10,Suh Cheolwon11,Leppä Sirpa1213,Rai Shinya14,Turgut Mehmet15,Jurczak Wojciech16,Cheung Matthew C.17,Gurion Ronit1819,Yeh Su-Peng20,Lopez-Hernandez Andres21,Dührsen Ulrich22,Thieblemont Catherine2324,Chiattone Carlos Sergio25,Balasubramanian Sriram26,Carey Jodi27,Liu Grace28,Shreeve S. Martin26,Sun Steven28,Zhuang Sen Hong28,Vermeulen Jessica29,Staudt Louis M.30,Wilson Wyndham30,

Affiliation:

1. Memorial Sloan Kettering Cancer Center, New York, NY

2. BC Cancer Agency, Vancouver, British Columbia, Canada

3. University of Southampton, Southampton, United Kingdom

4. “Seràgnoli” University of Bologna, Bologna, Italy

5. Fudan University, Shanghai, People’s Republic of China

6. Peking University Cancer Hospital, Beijing, People’s Republic of China

7. Azienda Ospedaliera Ospedali Riuniti Villa Sofia–Cervello, Palermo, Italy

8. Charles University, Hradec Králové, Czech Republic

9. University Hospital Hradec Králové, Hradec Králové, Czech Republic

10. Regional Clinical Hospital, Nizhny Novgorod, Russian Federation

11. University of Ulsan, Seoul, Republic of Korea

12. Helsinki University Hospital, Helsinki, Finland

13. University of Helsinki, Helsinki, Finland

14. Kindai University, Osakasayama, Japan

15. Ondokuz Mayis University, Samsun, Turkey

16. Jagiellonian University, Krakow, Poland

17. Sunnybrook Odette Cancer Centre, Toronto, Ontario, Canada

18. Rabin Medical Center, Petah Tikva, Israel

19. Tel Aviv University, Tel Aviv, Israel

20. China Medical University Hospital, Taichung, Republic of China

21. University Hospital Vall d’Hebron, Barcelona, Spain

22. University Hospital Essen, Essen, Germany

23. Hôpital Saint-Louis, Paris, France

24. Diderot University, Sorbonne Paris-Cité, Paris, France

25. Santa Casa Medical School, São Paulo, Brazil

26. Janssen Research and Development, San Diego, CA

27. Janssen Research and Development, Spring House, PA

28. Janssen Research and Development, Raritan, NJ

29. Janssen Research and Development, Leiden, the Netherlands

30. National Cancer Institute, National Institutes of Health, Bethesda, MD

Abstract

PURPOSE Ibrutinib has shown activity in non–germinal center B-cell diffuse large B-cell lymphoma (DLBCL). This double-blind phase III study evaluated ibrutinib and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in untreated non–germinal center B-cell DLBCL. PATIENTS AND METHODS Patients were randomly assigned at a one-to-one ratio to ibrutinib (560 mg per day orally) plus R-CHOP or placebo plus R-CHOP. The primary end point was event-free survival (EFS) in the intent-to-treat (ITT) population and the activated B-cell (ABC) DLBCL subgroup. Secondary end points included progression-free survival (PFS), overall survival (OS), and safety. RESULTS A total of 838 patients were randomly assigned to ibrutinib plus R-CHOP (n = 419) or placebo plus R-CHOP (n = 419). Median age was 62.0 years; 75.9% of evaluable patients had ABC subtype disease, and baseline characteristics were balanced. Ibrutinib plus R-CHOP did not improve EFS in the ITT (hazard ratio [HR], 0.934) or ABC (HR, 0.949) population. A preplanned analysis showed a significant interaction between treatment and age. In patients age younger than 60 years, ibrutinib plus R-CHOP improved EFS (HR, 0.579), PFS (HR, 0.556), and OS (HR, 0.330) and slightly increased serious adverse events (35.7% v 28.6%), but the proportion of patients receiving at least six cycles of R-CHOP was similar between treatment arms (92.9% v 93.0%). In patients age 60 years or older, ibrutinib plus R-CHOP worsened EFS, PFS, and OS, increased serious adverse events (63.4% v 38.2%), and decreased the proportion of patients receiving at least six cycles of R-CHOP (73.7% v 88.8%). CONCLUSION The study did not meet its primary end point in the ITT or ABC population. However, in patients age younger than 60 years, ibrutinib plus R-CHOP improved EFS, PFS, and OS with manageable safety. In patients age 60 years or older, ibrutinib plus R-CHOP was associated with increased toxicity, leading to compromised R-CHOP administration and worse outcomes. Further investigation is warranted.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

Cited by 417 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3