Reduced-dose cladribine (2-CdA) plus mitoxantrone is effective in the treatment of mantle-cell and low-grade non-Hodgkin's lymphoma.

Abstract Cladribine (2-chlorodeoxyadenosine) (2-CdA) has been shown to be effective in mantle-cell (MCL) and low-grade lymphomas (lgNHL). The aim of this multicentre study was to evaluate the rate and duration of remissions and to examine the toxicity of the combination of reduced-dose 2-CdA and mitoxantrone (CdM) in MCL and lgNHL as first-line therapy or for patients in their relapse. A total of 285 courses, median of five courses per patient, were administered to 62 evaluable patients (42 previously untreated, 20 relapsed) with 5 mg/m 2 2-CdA per day given as an intermittent 2-h infusion over 3 consecutive days combined with 8 mg/m 2 mitoxantrone on days 1 and 2 for the untreated patients or 12 mg/m 2 mitoxantrone on day 1 for patients in their first relapse for a maximum of six cycles every four weeks. 32 follicular, 18 MCL, 9 lymphoplasmacytoid, 2 marginal zone and 1 unclassified low-grade B-cell lymphoma were involved in the study. 56 of the 62 patients responded to CdM resulting in an overall response rate of 90% (95% confidence interval (CI), 80–96%) with a complete remission (CR) rate of 44% (95% CI, 31–57%) and a median duration of remission of 25 months (range 6–42+). The overall survival rate at 48 months was 80%. For 42 previously untreated patients, the overall response rate was 88% (95% CI, 74–96%) with a CR rate of 38% (95% CI, 24–54%), whereas the response rate for the group of 20 previously treated patients was similar with a 95% overall response (95% CI, 75–100%) and a CR rate of 55% (95% CI, 32–77%). In MCL, CdM showed a high activity, achieving a response rate of 100% (95% CI, 81–100%) with a CR rate of 44% and a median duration of remission of 24 months (range 6–35+). Myelosuppression was the major toxicity with 23% grade 3 granulocytopenia and 50% grade 4. Thrombocytopenia was less commonly observed, with only 8% grades 3 and 4. These results demonstrate that the combination of reduced-dose 2-CdA and mitoxantrone is a highly active regimen in the treatment of low-grade lymphomas, and in particular of MCL.