Switching from Azacitidine to Decitabine in MDS
Switching to decitabine after azacitidine failure is generally not recommended, as the available evidence shows minimal objective responses and poor outcomes, with most patients experiencing only disease stabilization at best. 1
Evidence Against Switching
The clinical data on sequential hypomethylating agent (HMA) use reveals disappointing results:
A retrospective study of 25 patients treated with decitabine after azacitidine failure showed zero complete or partial remissions and no hematologic improvement. Only 5 patients achieved stable disease, with median survival of just 5.9 months after decitabine initiation and most discontinuing after only 2 cycles due to progression or death. 2
The guideline consensus states that azacitidine and decitabine are "therapeutically relatively similar," suggesting limited biological rationale for expecting response to one agent after failure of the other. 1
Conflicting Evidence
One older, smaller study presents contradictory findings:
A 2008 study of 14 patients reported a 28% overall response rate (3 complete remissions, 1 hematologic improvement) with decitabine after azacitidine failure. 3 However, this conflicts sharply with the larger 2015 study showing zero objective responses. 2
The discrepancy may relate to the reason for azacitidine discontinuation: In the positive study, responders included patients who stopped azacitidine for toxicity (severe skin reaction) rather than true treatment failure. 3
When Switching Might Be Considered
The only scenario where decitabine after azacitidine may be reasonable is when azacitidine was discontinued due to intolerance or toxicity rather than disease progression or lack of response. 3
For patients with true azacitidine failure (progression or no response after 4-6 cycles):
- Consider clinical trial enrollment as the preferred option. 4
- Evaluate for allogeneic hematopoietic stem cell transplantation if eligible. 1, 4
- Transition to best supportive care if neither trial nor transplant is feasible. 1
Decitabine Dosing If Proceeding
Should you decide to use decitabine despite the unfavorable data:
The optimal schedule is 20 mg/m² intravenously daily for 5 consecutive days every 28 days, which showed superior complete response rates (39%) compared to alternative schedules in treatment-naïve patients. 1
Administer at least 4 cycles before declaring treatment failure, as responses may be delayed. 1
Monitor complete blood counts weekly during the first 2 cycles, then before each subsequent cycle, watching for grade 3-4 neutropenia which occurs in approximately 80% of patients. 5
Critical Pitfall to Avoid
Do not confuse "low-intensity therapy" with "low efficacy"—both HMAs require months of treatment commitment and are designed for patients with sufficient life expectancy to complete multiple cycles (typically 6+ months). 6 Switching HMAs in rapidly progressing disease wastes precious time that could be spent on more appropriate interventions like transplant evaluation or clinical trials. 4