Evidence for Selective Benefit of Sequential Treatment With Hypomethylating Agents in Patients With Myelodysplastic Syndrome.

BACKGROUND: Hypomethylating agents (HMAs) remain the mainstay of treatment of patients with myelodysplastic syndrome (MDS). Azacitidine is the only agent shown to improve overall survival in higher risk MDS. The sequential use of HMAs is common practice, given the limited alternatives. The response rate to azacitidine after decitabine is unknown. To investigate the potential benefit of this approach, we reviewed all cases of sequential HMA treatment.

PATIENTS AND METHODS: The Moffitt Cancer Center MDS database was reviewed, and 2 groups were identified. Group 1 had received decitabine after azacitidine failure and group 2 had received azacitidine after decitabine failure. The primary objective was to estimate the overall response rate according to the International Working Group 2006 criteria. The χ2 test and t test were used for the categorical and continuous variables, respectively. The Kaplan-Meier method was used to estimate the median overall survival.

RESULTS: The overall response rate for hematologic improvement or better was 63% in group 1% and 50% in group 2. The response to second-line treatment in groups 1 and 2 was 19% and 40%, respectively. The median overall survival for group 1 from diagnosis was 48 months and for group 2 was 100 months (P = .7).

CONCLUSION: Enrollment in clinical trials should be strongly encouraged in the case of HMA failure. Sequential use of HMAs could be considered as an alternative approach in the treatment of MDS after first-line HMA failure if clinical trials are not available. The outcomes of patients with progressive disease after treatment with HMAs remain poor and continue to be an unmet need.