Objectives: The aim of our study was to determine the feasibility, effectiveness and toxicity of combined regimens consisting of rituximab and cladribine (2-CdA) (RC) and RC plus cyclophosphamide (RCC) in the treatment of patients with recurrent or refractory chronic lymphocytic leukemia (CLL).
Methods: The RC regimen consisted of rituximab given on day 1 and 2-CdA (days 2-6). The RCC protocol included rituximab (day 1), 2-CdA (days 2-4) and cyclophosphamide given on days 2-4. The courses were re-administered at time intervals of 4 weeks or longer if severe myelosuppression occurred.
Results: Forty-six patients with CLL entered the study. Eighteen patients were treated with RC and 28 with RCC regimen. The median number of courses administered were three cycles (range 1-6). Three (6.5%) patients (95% CI: 1-14%) achieved a complete response and 31 (67%) patients (95% CI: 50-83%) a partial response. According to the particular regimen, the overall response rate was obtained in 12 (67%) patients treated with RC (95% CI: 45-89%) and in 22 patients (78%) treated with RCC (95% CI: 62-93%). The median progression free survival of responders to RC/RCC regimens was 12 months (range 4-46). Hypersensitivity to rituximab occurred in 16 (33%) patients, mostly during the first infusion of the drug. Grade 3/4 neutropenia was seen in six (13%) patients, grade 3/4 thrombocytopenia in three (9%) patients and grade 3/4 infections were observed in ten (28%) patients.
Conclusions: These data indicate that both RC and RCC regimens are feasible in heavily pretreated patients with CLL, showing also distinct therapeutic activity and relatively low toxicity, even in patients previously treated with cladribine-based protocols.