Consolidation and maintenance immunotherapy with rituximab improve clinical outcome in patients with B-cell chronic lymphocytic leukemia

Cancer. 2008 Jan 1;112(1):119-28. doi: 10.1002/cncr.23144.

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.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Murine-Derived
  • Disease-Free Survival
  • Drug Administration Schedule
  • Flow Cytometry
  • Humans
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Variable Region / genetics
  • Immunophenotyping
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Leukemia, Lymphocytic, Chronic, B-Cell / mortality
  • Middle Aged
  • Neoplasm, Residual
  • Rituximab
  • Survival Analysis

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Variable Region
  • Rituximab