Oral cladribine as primary therapy for patients with B-cell chronic lymphocytic leukemia

Purine analogs have wide potential indications in the treatment of hematologic malignancies, but intravenous administration has been required. We previously established that the oral bioavailability of cladribine is 50%. Our aim was to evaluate the efficacy and toxicity of oral cladribine to previously untreated patients with chronic lymphocytic leukemia (CLL).

Sixty-three patients with symptomatic but previously untreated CLL received cladribine solution 10 mg/m2/d orally for 5 consecutive days in monthly courses.

Complete remission (CR) was achieved in 24 patients (38%), and 23 patients (37%) had a partial response (PR). Most patients, including those in whom there was no remission (NR) achieved normal blood lymphocyte counts. Failure to meet response criteria was mostly due to thrombocytopenia. The median response duration was not reached at 2 years. The median survival time among 13 deceased patients was 322 days, whereas the median observation time of surviving patients is 760 days. The overall survival rate at 2 years is 82%. Response rate was associated with clinical stage. Grade III to IV infectious toxicity occurred in one third of patients.

Orally administered cladribine is an effective and feasible therapy for CLL, and produces durable remissions in three quarters of the patients. However, significant toxicity may occur and further studies are required to assess long-term effects and quality-of-life aspects.