REDUCED DOSE OF SUBCUTANEOUS CLADRIBINE INDUCES IDENTICAL RESPONSE RATES BUT DECREASED TOXICITY IN PRETREATED CHRONIC LYMPHOCYTIC-LEUKEMIA

Purpose: To study the efficacy and the safety of cladribine (2-chlorod eoxyadenosine, 2-CDA) administered as 24-hour infusions or as subcutan eous bolus injections at two different doses to patients with relapsin g or refractory chronic lymphocytic leukaemia (CLL), Patients and meth ods: In this non randomised 2-cohort study, 20 patients with pretreate d CLL received cladribine at a dose of 0.7 mg/kg/cycle as continuous i .v. infusions over seven days (group 1) and 35 patients were treated a t a reduced dose of 0.5 mg/kg/cycle given as s.c. bolus injections for five days (group 2). After two cycles of four week duration, response was assessed. In the case of progressive disease, therapy was discont inued, otherwise a maximum of four additional cycles were administered until best response. Results: A total of 130 cycles were administered (group 1: 41, group 2: 89). Patient characteristics in both groups we re comparable. The median dose intensities were 0.172 mg/kg per week a nd 0.123 mg/kg per week for groups 1 and 2, respectively (P less than or equal to 0.0001). The overall response rate for all 55 patients was 38% (95% confidence interval (95% CI): 25%-52%), with 5% CR and 33% P R. Response was similar in both patient groups (35% in group 1, 40% in group 2). No association between cladribine dose intensity and respon se rate was found, and there was no difference between patients relaps ing after or refractory to previous therapies (11 of 24 vs. 10 of 31). Median remission duration was six months in both groups. Toxicity, in particular infections (all WHO grades, 34% in group 1 versus 7% in gr oup 2) and myelosuppression (grade 1-4 neutropenia, 72% versus 41% of cladribine cycles) were statistically significantly more frequent in g roup 1. Conclusion. Cladribine is active in heavily pretreated patient s with chronic lymphocytic leukaemias. Dose reduction by 29% led to si milar response and remission duration, but to a significant decrease o f myelotoxicity and risk of infection. Cladribine administered as s.c. bolus injections at 0.5 mg/kg per cycle is safe and this dose level s hould not be exceeded in this patient population.