PURPOSE: The addition of rituximab to fludarabine-based regimens in chronic lymphocytic leukemia (CLL) has been shown to produce high response rates with extended remissions. The long-term follow-up of these regimens with respect to progression, survival, risk of secondary leukemia, and impact of genomic risk factors has been limited. METHODS: We report the long-term follow-up of the chemoimmunotherapy trial CALGB 9712 from the Cancer and Leukemia Group B, for which treatment regimen was previously reported, to examine end points of progression-free survival (PFS), overall survival (OS), impact of genomic features, and risk of therapy-related myeloid neoplasm (t-MN). RESULTS: A total of 104 patients were enrolled on this study and now have a median follow-up of 117 months (range, 66 to 131 months). The median OS was 85 months, and 71% of patients were alive at 5 years. The median PFS was 42 months, and 27% were progression free at 5 years. An estimated 13% remained free of progression at almost 10 years of follow-up. Multivariable models of PFS and OS showed that immunoglobulin heavy chain variable region mutational status was significant for both, whereas cytogenetic abnormalities were significant only for OS. No patient developed t-MN before relapse. CONCLUSION: Long-term follow-up of CALGB 9712 demonstrates extended OS and PFS with fludarabine plus rituximab. Patients treated with fludarabine plus rituximab administered concurrently or sequentially have a low risk of t-MN. These long-term data support fludarabine plus rituximab as one acceptable first-line treatment for symptomatic patients with CLL.
RCT Entities:
PURPOSE: The addition of rituximab to fludarabine-based regimens in chronic lymphocytic leukemia (CLL) has been shown to produce high response rates with extended remissions. The long-term follow-up of these regimens with respect to progression, survival, risk of secondary leukemia, and impact of genomic risk factors has been limited. METHODS: We report the long-term follow-up of the chemoimmunotherapy trial CALGB 9712 from the Cancer and Leukemia Group B, for which treatment regimen was previously reported, to examine end points of progression-free survival (PFS), overall survival (OS), impact of genomic features, and risk of therapy-related myeloid neoplasm (t-MN). RESULTS: A total of 104 patients were enrolled on this study and now have a median follow-up of 117 months (range, 66 to 131 months). The median OS was 85 months, and 71% of patients were alive at 5 years. The median PFS was 42 months, and 27% were progression free at 5 years. An estimated 13% remained free of progression at almost 10 years of follow-up. Multivariable models of PFS and OS showed that immunoglobulin heavy chain variable region mutational status was significant for both, whereas cytogenetic abnormalities were significant only for OS. No patient developed t-MN before relapse. CONCLUSION: Long-term follow-up of CALGB 9712 demonstrates extended OS and PFS with fludarabine plus rituximab. Patients treated with fludarabine plus rituximab administered concurrently or sequentially have a low risk of t-MN. These long-term data support fludarabine plus rituximab as one acceptable first-line treatment for symptomatic patients with CLL.
Authors: J C Byrd; T Murphy; R S Howard; M S Lucas; A Goodrich; K Park; M Pearson; J K Waselenko; G Ling; M R Grever; A J Grillo-Lopez; J Rosenberg; L Kunkel; I W Flinn Journal: J Clin Oncol Date: 2001-04-15 Impact factor: 44.544
Authors: S M O'Brien; H Kantarjian; D A Thomas; F J Giles; E J Freireich; J Cortes; S Lerner; M J Keating Journal: J Clin Oncol Date: 2001-04-15 Impact factor: 44.544
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Authors: K R Rai; B L Peterson; F R Appelbaum; J Kolitz; L Elias; L Shepherd; J Hines; G A Threatte; R A Larson; B D Cheson; C A Schiffer Journal: N Engl J Med Date: 2000-12-14 Impact factor: 91.245
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Authors: Vicki A Morrison; Kanti R Rai; Bercedis L Peterson; Jonathan E Kolitz; Laurence Elias; Frederick R Appelbaum; John D Hines; Lois Shepherd; Richard A Larson; Charles A Schiffer Journal: J Clin Oncol Date: 2002-09-15 Impact factor: 44.544
Authors: John D Hainsworth; Sharlene Litchy; John H Barton; Gerry Ann Houston; Robert C Hermann; James E Bradof; F Anthony Greco Journal: J Clin Oncol Date: 2003-05-01 Impact factor: 44.544
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Authors: F P Tambaro; G Garcia-Manero; S M O'Brien; S H Faderl; A Ferrajoli; J A Burger; S Pierce; X Wang; K-A Do; H M Kantarjian; M J Keating; W G Wierda Journal: Leukemia Date: 2015-08-20 Impact factor: 11.528
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 Journal: Leuk Lymphoma Date: 2015-03-30
Authors: John C Byrd; Amy S Ruppert; Nyla A Heerema; Alese E Halvorson; Eva Hoke; Mitchell R Smith; John E Godwin; Stephen Couban; Todd A Fehniger; Michael J Thirman; Martin S Tallman; Frederick R Appelbaum; Richard M Stone; Sue Robinson; Julie E Chang; Sumithra J Mandrekar; Richard A Larson Journal: Blood Adv Date: 2018-07-24