Oral therapy for myelodysplastic syndromes/neoplasms and acute myeloid leukemia: a revolution in progress

Patients with myeloid neoplasms such as myelodysplastic syndromes/neoplasms (MDS) and acute myeloid leukemia (AML) are generally older, and many are not eligible for curative intent intensive therapies and/or allogeneic hematopoietic stem cell transplantation. While lower intensity, hypomethylating agent (HMA)-based therapies such as azacitidine+venetoclax have improved patient outcomes significantly, responses are not durable, and most patients die from disease-related complications. The approvals of oral HMAs such as cedazuridine-decitabine (C-DEC) and oral azacitidine (CC-486) have kindled the hope that myeloid malignancies may soon be treated with total oral therapy.

We review all-oral therapies including the approvals of C-DEC and CC-486 in MDS and AML, respectively, in addition to emerging all-oral therapies, both monotherapy and combination, in higher-risk (HR) MDS and AML.

Oral HMAs have the potential to be a convenient and efficacy-equivalent treatment option for patients with HR-MDS or AML and improve their quality of life by reducing clinic visits for medication administration. Total-oral therapy combinations, largely including an oral HMA 'backbone,' are in the early phases of clinical development, and it is our hope that well-designed trials employing these agents may soon allow the identification of optimal regimens that deliver effective disease-directed therapy with good tolerability.