The outcome of patients with higher-risk myelodysplastic syndromes (MDS) after hypomethylating agent (HMA) failure is poor. This study evaluated the safety and activity of a combination of low-dose clofarabine and cytarabine for these patients.METHODS:
Seventy patients with higher-risk MDS who had no response, progressed, or relapsed after at least 4 cycles of HMA therapy were treated.RESULTS:
The median age was 72 years. Thirty-nine percent of the patients had high-risk disease according to the International Prognostic Scoring System, and 50% of the patients had poor-risk cytogenetics. Twenty-three percent of the patients had therapy-related MDS. The median number of prior cycles of HMA was 6 (range, 4-45). The overall response rate was 44%. The 6-week mortality rate was 9%. Grade 3 and higher nonhematologic toxicities were rare, but infections occurred in 52% of the patients, and fever of unknown origin occurred in 33%. The median overall survival (OS) was 10 months (95% confidence interval, 1-37 months). Thirteen percent of the patients underwent allogeneic stem cell transplantation. The responding patients had a median OS of 22 months, whereas the nonresponding patients had a median OS of 4 months. A complex karyotype was associated with worse response rates and OS.CONCLUSIONS:
The combination of low-dose clofarabine and cytarabine is clinically active in these patients with few treatment options.
The effectiveness of low-dose clofarabine and cytarabine in higher-risk myelodysplastic syndrome patients after hypomethylating agent failure is assessed. This dose combination is clinically active in these patients (especially those with diploid cytogenetics) and may be useful as a bridge to allogeneic stem cell transplantation in eligible patients.