For older adults with acute myeloid leukemia, the difference between treatment and no treatment has long been entangled with logistics — specifically, the need for frequent clinic visits to receive intravenous or subcutaneous therapy. A fully oral regimen that matches the efficacy of the current injectable standard could meaningfully expand access and reduce patient burden, particularly for those with limited mobility or who live far from infusion centers.
This phase 1–2, open-label multicenter trial enrolled 189 patients aged 75 or older, or those deemed ineligible for intensive induction chemotherapy, to receive the combination of oral decitabine-cedazuridine — a formulation designed to replicate the pharmacokinetics of intravenous decitabine — plus oral venetoclax. A key initial concern was whether decitabine-cedazuridine would alter venetoclax drug exposure through pharmacokinetic interaction; phase 1–2a data confirmed no clinically meaningful drug-drug interaction. In the pivotal phase 2b cohort of 101 patients, the complete response rate reached 47% (95% CI, 36–57%), a result that positions this all-oral combination as potentially comparable to the injectable azacitidine-venetoclax or decitabine-venetoclax regimens currently considered standard of care in this population.
The significance here extends beyond pharmacology. The injectable venetoclax-hypomethylating agent combinations have transformed outcomes for unfit AML patients since their approvals, but their administration model assumes reliable healthcare infrastructure access. An equivalent oral regimen could shift AML management toward a more patient-centered model. That said, several important caveats apply: this was a non-randomized trial without a head-to-head comparator arm, making efficacy comparisons to intravenous standards indirect. Myelosuppression was notable enough in phase 1 that schedule modifications were implemented in phase 2b to manage it, underscoring that tolerability optimization is still evolving. Longer-term survival data from this cohort — particularly overall survival and duration of response — will be critical before this can be declared a practice-changing advance. For now, this represents a promising and logistically meaningful proof of concept warranting a definitive randomized trial.