Opinion
Video
Place in Therapy for Oral Combinations in Relapsed/Refractory AML
Author(s):
A panelist discusses how oral combination therapy with decitabine-cedazuridine plus venetoclax shows activity in the relapsed/refractory acute myeloid leukemia setting, achieving responses even in patients with TP53 mutations, prior venetoclax exposure, or prior transplant, though the presenter questions whether 10 days of decitabine offers advantages over the standard 5-day regimen and emphasizes that these oral therapies can effectively extend beyond frontline treatment into salvage settings.
The MD Anderson group has developed a combination therapy using 10 days of intravenous decitabine with venetoclax for relapsed/refractory acute myeloid leukemia (AML), building on historical use of extended decitabine regimens, particularly in patients with TP53 mutations in both myelodysplastic syndrome and AML settings. However, a randomized study from the same institution comparing 10-day vs 5-day decitabine regimens showed no significant outcome differences. Most patients typically transition from 10 days to 5 days within few cycles due to significant myelosuppression associated with prolonged decitabine and venetoclax combination therapy, raising questions about the necessity of the extended regimen duration.
The ASCO presentation reported results from an all-oral version of this approach, using 10 days of oral decitabine with venetoclax in the relapsed/refractory setting. Twenty patients were treated in this challenging population, with most requiring rapid reduction to 5 days of oral decitabine due to toxicity. Despite significant myelosuppression, the treatment was generally well tolerated and demonstrated encouraging activity, with some patients achieving responses even after prior venetoclax exposure or transplantation. The overall survival reached approximately 8.5 months, and several patients were successfully bridged to transplantation, representing meaningful outcomes in this refractory population.
The key clinical takeaway emphasizes that double oral therapy maintains activity in the relapsed/refractory AML setting, even in high-risk patients with TP53 mutations, prior venetoclax exposure, or previous transplantation. However, the extended 10-day decitabine duration may not provide additional advantages over standard 5-day regimens with continuous venetoclax and appropriate dose adjustments. The data reinforce the potential for oral combination therapies beyond frontline treatment, requiring similar vigilance regarding myelosuppression monitoring, aggressive supportive care, drug interaction screening, and compliance assessment. This expands the potential application of convenient oral regimens across different treatment settings in AML management.
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