Clofarabine: An Unclear Role in Lymphoma Care
To date, studies of clofarabine in patients with lymphoma have been limited by small patient numbers and myelosuppression toxicities.
Clofarabine is a second-generation purine nucleoside antimetabolite that inhibits DNA synthesis and repair. Intravenous clofarabine at a 52 mg/m2 dose is approved for pediatric patients with relapsed or refractory acute lymphoblastic leukemia who progress after treatment with at least 2 prior regimens.1
In trials of clofarabine in pediatric leukemia, the drug induced complete responses in a population of patients aged 1 to 21 years, though no improvement in survival was shown.2
Similar studies in adults with relapsed or refractory acute leukemia showed that clofarabine is active and safe in patients with hematologic malignancies. Yet to date, studies of clofarabine in patients with lymphoma have been limited by small patient numbers and myelosuppression toxicities.
A recent study by Foss et al published in The Oncologist showed that clofarabine can be active in relapsed and refractory lymphoma, though responses were seen only in patients with T-cell lymphomas.3 The study enrolled 14 patients (10 with T-cell non-Hodgkin lymphoma [NHL] and 4 with B-cell NHL). The starting dose was 10 mg/m2 per week administered for 3 weeks every 28 days. Four patients were enrolled at 10 mg/m2, 4 at 15 mg/m2, 3 at 20 mg/m2, 2 at 30 mg/m2, and 1 at 40 mg/m2.
One patient with cutaneous T-cell lymphoma had a partial response; this patient had stage III erythroderma and was treated with the 10 mg/m2 dose. Five patients with T-cell lymphoma had stable disease, and 8 patients had no response to treatment. On this weekly dosing schedule, no maximum tolerated dose (MTD) was observed.
This study was initiated after the results of an earlier trial showed myelosuppression to be a major dose-limiting toxicity of clofarabine in patients with relapsed or refractory NHL.4
That study, by Nabhan et al, was conducted in patients with relapsed or refractory B-cell lymphoma only. It included 33 patients who were treated with 4 or 6 mg/m2 clofarabine infusions daily for 5 days given every 28 days.
The overall response rate was 42%, with 23% of patients reaching a complete response and 19% reaching a partial response. The response rate among patients refractory to rituximab was 47%.
Reversible myelosuppression was, however, a major toxicity, and more than 60% of patients had neutropenia or thrombocytopenia. The MTD was 4 mg/m2, a dose that is “significantly less than the doses used in the acute leukemia trials in which myelosuppression was considered acceptable.”3
Foss and colleagues noted that, based on their study of 10 mg/m2 weekly clofarabine, “it is unclear whether clofarabine has meaningful clinical activity in T-cell lymphomas.”