Cytogenetic prioritization with inclusion of molecular markers predicts outcome in previously untreated patients with chronic lymphocytic leukemia treated with fludarabine or fludarabine plus cyclophosphamide: a long-term follow-up study of the US intergroup phase III trial E2997
Year: 2015
Type: article
Abstract: Fludarabine (F) and cyclophosphamide (C) remain backbones of up-front chemotherapy regimens for chronic lymphocytic leukemia (CLL). We report long-term follow-up of a randomized F vs. FC trial in untreated CLL (#) . With median follow-up of 88 months, estimated median progression-free survival (PFS) was 19.3 vs. 48.1 months for F (n = 109) and FC (n = 118), respectively (p < 0.0001), and median overall survival (OS) was 88.0 vs. 79.1 months (p = 0.96). In multivariable analyses, variables associated with inferior PFS and OS respectively were age (p = 0.002, p < 0.001), Rai stage (p = 0.006, p = 0.02) and sex (p = 0.03, PFS only). Del(17)(p13.1) predicted shorter PFS and OS (p < 0.0001 for each), as did del(11q)(22.3) (p < 0.0001, p = 0.005, respectively), trisomy 12 with mutated Notch1 (p = 0.003, p = 0.03, respectively) and unmutated IGHV (p = 0.009, p = 0.002, respectively), all relative to patients without these features. These data confirm results from shorter follow-up and further justify targeted therapies for CLL.
Authors: David M. Lucas, Amy S. Ruppert, Gerard Lozanski, Gordon W. Dewald, Arletta Lozanski, Rainer Claus, Christoph Plass, Ian W. Flinn, Donna S. Neuberg, Elisabeth M. Paietta, John M. Bennett, Diane F. Jelinek, John G. Gribben, Mohamad A. Hussein, Frederick R. Appelbaum, Richard A. Larson, Dennis F. Moore, Martin S. Tallman, John C. Byrd, Michael R. Grever
Institutions: The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Wexner Medical Center, The Ohio State University, Mayo Clinic, University of Freiburg, German Cancer Research Center, University Medical Center Freiburg, Sarah Cannon, Tennessee Oncology, Dana-Farber Cancer Institute, Montefiore Medical Center, University of Rochester, Queen Mary University of London, Barts Cancer Institute, Celgene (United States), Fred Hutch Cancer Center, University of Chicago, Cancer Center of Kansas, Memorial Sloan Kettering Cancer Center
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1105606313, G1257575315, ECOG Statistical Office Data Management Grant, G1422427855, G1545560008, G1814228702, ECOG-ACRIN Network Group Operations Center, G1938688226, G1958973285, Network Lead Academic Participating Site: Memorial Sloan-Kettering Cancer Center, G2017411191, G2056719604, G2215807464, Experimental Therapeutics of Leukemia, G2679961467, DNA Methylation & Chromatin Modifications: Mechanisms & Applications in Cancer*, G2750730928, G286468852, G3100437649, G332150848, G3475623468, G3578465708, G36541222, G3737421695, SWOG Network Group Operations Center of the NCTN, G3762168461, G3800835027, G3996959562, ECOG Clinical Trials, G4205753748, Southwest Oncology Group, G4289182410, G4412485521, Southwest Oncology Group, G5020521663, G5417201949, G5672437777, G5765316850, G608154585, Cancer and Leukemia Group B, G6710502012, ECOG-ACRIN Network Group Statistics and Data Management Center, G6944741171, Eastern Cooperative Oncology Group Operations Office, Chronic Lymphocytic Leukemia Research Consortium, Cancer Center Support Grant, G92717670, G944802235, G964706321, G973482110
OpenAlex ID: W2171004514