title: Consolidation and maintenance immunotherapy with rituximab improve clinical outcome in patients with B-cell chronic lymphocytic leukemia.
abstract: BACKGROUND
  Rituximab in sequential combination with fludarabine (Flu) allowed patients with B-cell chronic lymphocytic leukemia (B-CLL) to achieve higher remission rates and longer response duration. Based on their recent experience in indolent non-Hodgkin lymphomas, in this study, the authors attempted to demonstrate whether consolidation/maintenance therapy with rituximab could prolong the response duration in this patient population.
  
  
  METHODS
  This Phase II study was based on a consolidation/maintenance therapy with rituximab for patients in complete remission (CR) or partial remission (PR) who were positive for minimal residual disease (MRD), as determined by flow cytometry. Seventy-five symptomatic, untreated patients with B-CLL received 6 monthly cycles of Flu (25 mg/m(2) for 5 days) followed by 4 weekly doses of rituximab (375 mg/m(2)). Then, 28 patients who were positive for MRD were consolidated with 4 monthly cycles of rituximab (375 mg/m(2)) followed by 12 monthly low doses of rituximab (150 mg/m(2)).
  
  
  RESULTS
  Based on National Cancer Institute criteria, 61 of 75 patients (81%) achieved a CR, 10 of 75 patients (13%) had a PR, and 4 of 75 patients (5%) had either no response or disease progression. MRD-positive patients in CR or PR who received consolidation therapy (n = 28 patients) had a significantly longer response duration (87% vs 32% at 5 years; P = .001) compared with a subset of patients who did not receive consolidation therapy (n = 18 patients). All patients experienced a long progression-free survival from the end of induction treatment (73% at 5 years). It was noteworthy that, within the subset of ZAP-70-positive patients, MRD-positive, consolidated patients (n = 12 patients) had a significantly longer response duration (69% vs 0% at 2.6 years; P = .007) compared with MRD-positive, unconsolidated patients (n = 11 patients).
  
  
  CONCLUSIONS
  The addition of a consolidation and maintenance therapy with rituximab prolonged response duration significantly in patients with MRD-positive B-CLL.
authors.affiliation: Department of Hematology, University Tor Vergata, S. Eugenio Hospital, Rome, Italy. g.delpoeta@tin.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Del Poeta
authors.forename: Maria Ilaria
authors.initials: MI
authors.lastname: Del Principe
authors.forename: Francesco
authors.initials: F
authors.lastname: Buccisano
authors.forename: Luca
authors.initials: L
authors.lastname: Maurillo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Capelli
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Luciano
authors.forename: Alessio Pio
authors.initials: AP
authors.lastname: Perrotti
authors.forename: Massimo
authors.initials: M
authors.lastname: Degan
authors.forename: Adriano
authors.initials: A
authors.lastname: Venditti
authors.forename: Paolo
authors.initials: P
authors.lastname: de Fabritiis
authors.forename: Valter
authors.initials: V
authors.lastname: Gattei
authors.forename: Sergio
authors.initials: S
authors.lastname: Amadori
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005434:Flow Cytometry; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D016130:Immunophenotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D018365:Neoplasm, Residual; D000069283:Rituximab; D016019:Survival Analysis
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D000069283:Rituximab