Poor outcome of patients with myelodysplastic syndrome after azacitidine treatment failure

Background: Limited data have been reported describing the outcome and prognosis of patients with MDS in whom treatment with azanucleosides has failed. We report our single-institutional experience of patients with higher-risk MDS in whom therapy with azacitidine has failed.

Patients and methods: This was a retrospective study of MDS patients treated at the Moffitt Cancer Center in whom azacitidine treatment regimens had failed. Patients were identified through the Moffitt database, and clinical data were extracted. Azacitidine failure was defined as failure to achieve hematologic improvement or better after at least 4 cycles of therapy, loss of response, or disease progression during therapy. The objectives were to characterize response to salvage therapies after azacitidine failure and to estimate the overall survival. All responses were defined according to the International Working Group 2006 criteria, and survival was estimated using the Kaplan-Meier method.

Results: A total of 59 patients in whom azacitidine treatment had failed were identified. The median age at treatment failure was 68 years, and most were Caucasian male patients. Thirteen patients received intensive chemotherapy with an overall response rate of 31%. Six patients were treated with decitabine, and none responded. Median overall survival of the entire cohort after azacitidine failure was 5.8 months (95% confidence interval, 1.3-10.3 months), with an estimated 12-month survival of 17%.

Conclusion: Patients with higher-risk MDS in whom azacitidine treatment has failed have a poor prognosis and low probability of response to salvage treatments. The standard of care after azanucleoside failure should be enrollment in clinical trials.