title: Addition of rituximab to fludarabine may prolong progression-free survival and overall survival in patients with previously untreated chronic lymphocytic leukemia: an updated retrospective comparative analysis of CALGB 9712 and CALGB 9011.
abstract: Fludarabine and rituximab combination therapies in chronic lymphocytic leukemia (CLL) have yielded promising early results, but no comparative efficacy data relative to standard fludarabine treatment regimens have been reported. To assess the effect of the addition of rituximab to fludarabine therapy, we retrospectively compared the treatment outcome of patients with similar clinical characteristics enrolled on 2 multicenter clinical trials performed by the Cancer and Leukemia Group B and the US Intergroup that used fludarabine and rituximab (CALGB 9712, n = 104) or fludarabine (CALGB 9011, n = 178). In multivariate analyses controlling for pretreatment characteristics, the patients receiving fludarabine and rituximab had a significantly better progression-free survival (PFS; P < .0001) and overall survival (OS; P = .0006) than patients receiving fludarabine therapy. Two-year PFS probabilities were 0.67 versus 0.45, and 2-year OS probabilities were 0.93 versus 0.81. Infectious toxicity was similar between the 2 treatment approaches. These comparative data are retrospective and could be confounded by differences in supportive care or dissimilar enrollment of genetic subsets on each trial. Confirmation of these findings will require a prospective randomized trial comparing fludarabine and rituximab to fludarabine.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, The Ohio State University, Columbus, OH 43210, USA. byrd3@medctr.osu.edu
authors.forename: John C
authors.initials: JC
authors.lastname: Byrd
authors.forename: Kanti
authors.initials: K
authors.lastname: Rai
authors.forename: Bercedis L
authors.initials: BL
authors.lastname: Peterson
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Appelbaum
authors.forename: Vicki A
authors.initials: VA
authors.lastname: Morrison
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Kolitz
authors.forename: Lois
authors.initials: L
authors.lastname: Shepherd
authors.forename: John D
authors.initials: JD
authors.lastname: Hines
authors.forename: Charles A
authors.initials: CA
authors.lastname: Schiffer
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols; D002986:Clinical Trials as Topic; D018450:Disease Progression; D006801:Humans; D007167:Immunotherapy; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008875:Middle Aged; D012189:Retrospective Studies; D000069283:Rituximab; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D014740:Vidarabine; C024352:fludarabine