A phase II study of low dose intravenous clofarabine for elderly patients with myelodysplastic syndrome who have failed 5-azacytidine

Abstract

The treatment options for patients with myelodysplastic syndrome (MDS) who have failed DNA hypomethylating agents are limited. In this study, we set out to investigate the efficacy of low dose clofarabine in 10 patients with MDS (four intermediate-2/high risk disease) who had failed 5-azacytidine. The median age was 73 years (range 65–78) and median cycles of clofarabine received were 2 (range 1–4). Nine patients were evaluable for response. An overall response rate of 44% was observed (one CR, one PR, and two HI). All responders had low risk disease. The median duration of response was 12 months (range 6.5–15.5). Although the doses of clofarabine administered were only 12.5–25% of that used in other studies, significant hematologic toxicities were observed. Severe and prolonged pancytopenia occurred in all 10 patients. One patient who had a history of thrombocytopenic gastrointestinal bleed died due to an intracranial bleed despite aggressive platelet support. Low dose clofarabine may, therefore, induce response, but with significant toxicities, in patients with low risk MDS who fail 5-azacytidine. Future work involving a larger patient population is needed to establish the role of low dose clofarabine in low risk MDS.

Keywords:

• Clofarabine
• MDS
• 5-azacytidine failers

Declaration of interest: This study was supported by Genzyme Corporation, Cambridge, MA, USA.