Munir, T, Howard, DR orcid.org/0000-0003-3333-9783, McParland, L et al. (12 more authors) (2017) Results of the randomized phase IIB ADMIRE trial of FCR with or without mitoxantrone in previously untreated CLL. Leukemia, 31 (10). pp. 2085-2093. ISSN 0887-6924
Abstract
ADMIRE was a multi-center, randomized-controlled, open, phase IIB superiority trial in previously untreated Chronic Lymphocytic Leukemia (CLL). Conventional frontline therapy in fit patients is fludarabine, cyclophosphamide and rituximab (FCR). Initial evidence from non-randomized Phase II trials suggested that the addition of mitoxantrone to FCR (FCM-R) improved remission rates. 215 patients were recruited to assess the primary endpoint of complete remission (CR) rates according to IWCLL criteria. Secondary endpoints were progression-free survival (PFS), overall survival (OS), overall response rate, minimal residual disease (MRD) negativity and safety. At final analysis, CR rates were 69.8% FCR vs 69.3% FCM-R [adjusted odds ratio (OR): 0.97; 95%CI: (0.53-1.79), P=0.932]. MRD-negativity rates were 59.3% FCR vs 50.5% FCM-R [adjusted OR: 0.70; 95% CI: (0.39-1.26), P=0.231]. During treatment, 60.0% (n=129) of participants received G-CSF as secondary prophylaxis for neutropenia, a lower proportion on FCR compared with FCM-R (56.1 vs 63.9%). The toxicity of both regimens was acceptable. There are no significant differences between the treatment groups for PFS and OS. The trial demonstrated that the addition of mitoxantrone to FCR did not increase the depth of response. Oral FCR was well tolerated and resulted in impressive responses in terms of CR rates and MRD negativity compared to historical series with intravenous chemotherapy.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 Macmillan Publishers Limited. All rights reserved. This is an author produced version of a paper published in Leukemia. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Chronic lymphocytic leukaemia; Randomized controlled trials |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > Institute of Molecular Medicine (LIMM) (Leeds) > Section of Experimental Haematology (Leeds) |
Funding Information: | Funder Grant number Roche Products Ltd NOT GIVEN |
Depositing User: | Symplectic Publications |
Date Deposited: | 26 Apr 2017 11:36 |
Last Modified: | 15 Nov 2017 16:33 |
Published Version: | https://doi.org/10.1038/leu.2017.65 |
Status: | Published |
Publisher: | Nature Publishing Group |
Identification Number: | 10.1038/leu.2017.65 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:115669 |