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Keywords:

  • B-cell chronic lymphocytic leukemia;
  • minimal residual disease;
  • consolidation and maintenance therapy with rituximab;
  • ZAP-70;
  • CD38;
  • immunoglobulin heavy-chain variable-region status;
  • cytogenetics;
  • response duration

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/m2 for 5 days) followed by 4 weekly doses of rituximab (375 mg/m2). Then, 28 patients who were positive for MRD were consolidated with 4 monthly cycles of rituximab (375 mg/m2) followed by 12 monthly low doses of rituximab (150 mg/m2).

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 withrituximab prolonged response duration significantly in patients with MRD-positive B-CLL. Cancer 2008. © 2007 American Cancer Society.