Chronic Lymphocytic Leukemia Therapy Guided by Measurable Residual Disease.


Munir, T, Cairns, DA, Bloor, A, Allsup, D, Cwynarski, K, Pettitt, A ORCID: 0000-0002-0907-8950, Paneesha, S, Fox, CP, Eyre, TA, Forconi, F et al (show 22 more authors) (2024) Chronic Lymphocytic Leukemia Therapy Guided by Measurable Residual Disease. New England Journal of Medicine, 390 (4). pp. 326-337. ISSN 0028-4793, 1533-4406

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Abstract

Background The combination of ibrutinib and venetoclax has been shown to improve outcomes in patients with chronic lymphocytic leukemia (CLL) as compared with chemoimmunotherapy. Whether ibrutinib-venetoclax and personalization of treatment duration according to measurable residual disease (MRD) is more effective than fludarabine-cyclophosphamide-rituximab (FCR) is unclear. Methods In this phase 3, multicenter, randomized, controlled, open-label platform trial involving patients with untreated CLL, we compared ibrutinib-venetoclax and ibrutinib monotherapy with FCR. In the ibrutinib-venetoclax group, after 2 months of ibrutinib, venetoclax was added for up to 6 years of therapy. The duration of ibrutinib-venetoclax therapy was defined by MRD assessed in peripheral blood and bone marrow and was double the time taken to achieve undetectable MRD. The primary end point was progression-free survival in the ibrutinib-venetoclax group as compared with the FCR group, results that are reported here. Key secondary end points were overall survival, response, MRD, and safety. Results A total of 523 patients were randomly assigned to the ibrutinib-venetoclax group or the FCR group. At a median of 43.7 months, disease progression or death had occurred in 12 patients in the ibrutinib-venetoclax group and 75 patients in the FCR group (hazard ratio, 0.13; 95% confidence interval [CI], 0.07 to 0.24; P<0.001). Death occurred in 9 patients in the ibrutinib-venetoclax group and 25 patients in the FCR group (hazard ratio, 0.31; 95% CI, 0.15 to 0.67). At 3 years, 58.0% of the patients in the ibrutinib-venetoclax group had stopped therapy owing to undetectable MRD. After 5 years of ibrutinib-venetoclax therapy, 65.9% of the patients had undetectable MRD in the bone marrow and 92.7% had undetectable MRD in the peripheral blood. The risk of infection was similar in the ibrutinib-venetoclax group and the FCR group. The percentage of patients with cardiac serious adverse events was higher in the ibrutinib-venetoclax group than in the FCR group (10.7% vs. 0.4%). Conclusions MRD-directed ibrutinib-venetoclax improved progression-free survival as compared with FCR, and results for overall survival also favored ibrutinib-venetoclax. (Funded by Cancer Research UK and others; FLAIR ISRCTN Registry number, ISRCTN01844152; EudraCT number, 2013-001944-76.)

Item Type: Article
Uncontrolled Keywords: National Cancer Research Institute Chronic Lymphocytic Leukemia Subgroup, Humans, Neoplasm, Residual, Sulfonamides, Cyclophosphamide, Vidarabine, Antineoplastic Combined Chemotherapy Protocols, Time Factors, Leukemia, Lymphocytic, Chronic, B-Cell, Rituximab, Bridged Bicyclo Compounds, Heterocyclic, Duration of Therapy
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: 09 Jan 2024 11:27
Last Modified: 23 Jan 2026 23:27
DOI: 10.1056/NEJMoa2310063
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3177737
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