Consolidation and maintenance immunotherapy with rituximab improve clinical outcome in patients with B-cell chronic lymphocytic leukemia.
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.
Del Poeta
Giovanni
G
Department of Hematology, University Tor Vergata, S. Eugenio Hospital, Rome, Italy. g.delpoeta@tin.it
Del Principe
Maria Ilaria
MI
Buccisano
Francesco
F
Maurillo
Luca
L
Capelli
Giovanni
G
Luciano
Fabrizio
F
Perrotti
Alessio Pio
AP
Degan
Massimo
M
Venditti
Adriano
A
de Fabritiis
Paolo
P
Gattei
Valter
V
Amadori
Sergio
S
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
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D000069283:Rituximab