Measurable Residual Disease-Guided Therapy for Chronic Lymphocytic Leukemia.

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Munir, Talha, Girvan, Sean, Cairns, David A, Bloor, Adrian, Allsup, David, Varghese, Abraham M, Gohil, Satyen, Paneesha, Shankara, Pettitt, Andrew ORCID: 0000-0002-0907-8950, Eyre, Toby et al (show 26 more authors) , Fox, Christopher P, Forconi, Francesco ORCID: 0000-0002-2211-1831, Kennedy, Ben, Balotis, Constantine, Pemberton, Nicholas, Sheehy, Oonagh, Gribben, John, Elmusharaf, Nagah, Gatto, Simona, Preston, Gavin, Schuh, Anna, Walewska, Renata, Duley, Lelia ORCID: 0000-0001-6721-5178, Webster, Nichola, Dalal, Surita, Rawstron, Andrew, Howard, Dena, Hockaday, Anna, Jackson, Sharon, Greatorex, Natasha, Bell, Sue, Stones, David ORCID: 0000-0002-2719-7064, Brown, Julia M, Patten, Piers EM, Hillmen, Peter and UK CLL Trials Group (2025) Measurable Residual Disease-Guided Therapy for Chronic Lymphocytic Leukemia. The New England journal of medicine, 393 (12). pp. 1177-1190. ISSN 0028-4793, 1533-4406

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Abstract

<h4>Background</h4>An interim analysis of progression-free survival in this trial showed that ibrutinib-venetoclax was superior to fludarabine-cyclophosphamide-rituximab (FCR) among patients with chronic lymphocytic leukemia (CLL). Whether ibrutinib-venetoclax is more effective than ibrutinib alone is unclear.<h4>Methods</h4>In this phase 3, multicenter, open-label trial, we randomly assigned patients with CLL to receive ibrutinib-venetoclax, ibrutinib alone, or FCR. The primary end points were undetectable measurable residual disease (MRD) in bone marrow within 2 years in the ibrutinib-venetoclax group as compared with the ibrutinib-alone group and progression-free survival in the ibrutinib-venetoclax group as compared with the FCR group. A powered secondary end point was progression-free survival in the ibrutinib-venetoclax group as compared with the ibrutinib-alone group. Other secondary end points included overall survival.<h4>Results</h4>A total of 172 of the 260 participants (66.2%) in the ibrutinib-venetoclax group had undetectable MRD in bone marrow within 2 years, as compared with none of the 263 participants in the ibrutinib-alone group (P<0.001) and 127 of the 263 participants (48.3%) in the FCR group. With a median follow-up of 62.2 months, disease progression or death occurred in 18 participants (6.9%) in the ibrutinib-venetoclax group, as compared with 59 (22.4%) in the ibrutinib-alone group (hazard ratio, 0.29; 95% confidence interval [CI], 0.17 to 0.49; P<0.001) and 112 (42.6%) in the FCR group (hazard ratio, 0.13; 95% CI, 0.08 to 0.21; P<0.001). Progression-free survival at 5 years was 93.9% with ibrutinib-venetoclax, 79.0% with ibrutinib alone, and 58.1% with FCR. Death occurred in 11 participants (4.2%) in the ibrutinib-venetoclax group, as compared with 26 (9.9%) in the ibrutinib-alone group (hazard ratio, 0.41; 95% CI, 0.20 to 0.83) and 39 (14.8%) in the FCR group (hazard ratio, 0.26; 95% CI, 0.13 to 0.50). Sudden death occurred in 3, 8, and 4 participants in the ibrutinib-venetoclax, ibrutinib-alone, and FCR groups, respectively.<h4>Conclusions</h4>With extended follow-up and increased enrollment, our trial showed that undetectable MRD and extended progression-free survival were more common with ibrutinib-venetoclax than with ibrutinib alone or FCR. The results for overall survival were also consistent with a benefit of ibrutinib-venetoclax. (Funded by Cancer Research UK and others; FLAIR ISRCTN Registry number, ISRCTN01844152; EudraCT number, 2013-001944-76.).

Item Type:	Article
Uncontrolled Keywords:	UK CLL Trials Group, Bone Marrow, Humans, Neoplasm, Residual, Sulfonamides, Cyclophosphamide, Piperidines, Pyrazoles, Pyrimidines, Adenine, Vidarabine, Antineoplastic Combined Chemotherapy Protocols, Follow-Up Studies, Adult, Aged, Middle Aged, Female, Male, Leukemia, Lymphocytic, Chronic, B-Cell, Rituximab, Bridged Bicyclo Compounds, Heterocyclic, Progression-Free Survival, Tyrosine Kinase Inhibitors
Divisions:	Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Systems, Molec & Integrative Biology > Inst. Systems, Molec & Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	01 Jul 2025 09:43
Last Modified:	22 Nov 2025 22:39
DOI:	10.1056/nejmoa2504341
Related Websites:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3193496
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