Younes, Anas, Sehn, Laurie H., Johnson, Peter ORCID: 0000-0003-2306-4974, Zinzani, Pier Luigi, Hong, Xiaonan, Zhu, Jun, Patti, Caterina, Belada, David ORCID: 0000-0002-4981-6188, Samoilova, Olga, Suh, Cheolwon, Leppae, Sirpa, Rai, Shinya, Turgut, Mehmet, Jurczak, Wojciech ORCID: 0000-0003-1879-8084, Cheung, Matthew C., Gurion, Ronit, Yeh, Su-Peng, Lopez-Hernandez, Andres, Duehrsen, Ulrich, Thieblemont, Catherine, Chiattone, Carlos Sergio, Balasubramanian, Sriram, Carey, Jodi, Liu, Grace, Shreeve, S. Martin, Sun, Steven, Zhuang, Sen Hong, Vermeulen, Jessica, Staudt, Louis M., Wilson, Wyndham, Fisher, Richard I., Engert, Andreas, Stadtmauer, Edward A. and Wei, Lee-Jen (2019). 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. J. Clin. Oncol., 37 (15). S. 1285 - 1307. ALEXANDRIA: AMER SOC CLINICAL ONCOLOGY. ISSN 1527-7755

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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. (C) 2019 by American Society of Clinical Oncology

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Younes, AnasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sehn, Laurie H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Johnson, PeterUNSPECIFIEDorcid.org/0000-0003-2306-4974UNSPECIFIED
Zinzani, Pier LuigiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hong, XiaonanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhu, JunUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Patti, CaterinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Belada, DavidUNSPECIFIEDorcid.org/0000-0002-4981-6188UNSPECIFIED
Samoilova, OlgaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Suh, CheolwonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leppae, SirpaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rai, ShinyaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Turgut, MehmetUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jurczak, WojciechUNSPECIFIEDorcid.org/0000-0003-1879-8084UNSPECIFIED
Cheung, Matthew C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gurion, RonitUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yeh, Su-PengUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lopez-Hernandez, AndresUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Duehrsen, UlrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thieblemont, CatherineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chiattone, Carlos SergioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Balasubramanian, SriramUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Carey, JodiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liu, GraceUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shreeve, S. MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sun, StevenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhuang, Sen HongUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vermeulen, JessicaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Staudt, Louis M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wilson, WyndhamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fisher, Richard I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Engert, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stadtmauer, Edward A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wei, Lee-JenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-148045
DOI: 10.1200/JCO.18.02403
Journal or Publication Title: J. Clin. Oncol.
Volume: 37
Number: 15
Page Range: S. 1285 - 1307
Date: 2019
Publisher: AMER SOC CLINICAL ONCOLOGY
Place of Publication: ALEXANDRIA
ISSN: 1527-7755
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
R-CHOP; GENE-EXPRESSION; THERAPY; PLACEBOMultiple languages
OncologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/14804

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