Fewer infections, but maintained antitumor activity with lower-dose versus standard-dose cladribine in pretreated low-grade non-Hodgkin's lymphoma

Purpose: To study the efficacy and the safety of cladribine (2-chlorodeoxyadenosine [2-CDA]) administered at two different dosages. Patients and Methods: In this two-cohort study, patients with low-grade refractory/relapsing non-Hodgkin's lymphoma (NHL) received 2-CDA at a dose of 0.7 mg/kg per cycle as a continuous intravenous (IV) infusion (group 1, n = 44) or at a reduced dose of 0.5 mg/kg per cycle as a subcutaneous (SC) bolus injection (group 2, n = 60). Three 2-CDA cycles at greater than or equal to 4-week intervals were planned, then treatment could be pursued until six cycles. Results: A total of 300 cycles were administered (group 1, 114 cycles; group 2, 186). Patient characteristics in both groups were comparable. The median dose-intensities were 0.17 mg/kg/wk and 0.13 mg/kg/wk for groups 1 and 2, respectively (P less than or equal to .0001). The overall response rate for all 104 patients was 54% (95% confidence interval [CI], 45% to 66%; 15% complete response [CR] and 39% partial response [PR]). Response was similar in both patient groups (57% in group 1 and 53% in group 2; P = .72), and no association between 2-CDA dose-intensity and response rate was found (P = .35). Median remission duration was 7 and 12 months in groups 1 and 2, respectively (P = .21). Toxicity, in particular opportunistic infections (a grade 2, 30% in group 1 v 7% in group 2; P = .003) and myelosuppression (greater than or equal to grade 3 neutropenia, 33% v8% of 2-CDA cycles, P < .0001), were more frequent in group 1. Multiple logistic regression analysis showed that the infection risk (grade greater than or equal to 2) was decreased by 81% with 2-CDA dose reduction in group 2 after adjusting for number of pretreatment regimens and time since diagnosis (P = .01). Conclusion: When administered as a SC bolus injection, 2-CDA 0.5 mg/kg per cycle is safe and this dose level should not be exceeded in this patient population. (C) 1998 by American Society of Clinical Oncology.