Oral hypomethylating agents: beyond convenience in MDS

Abstract

Oral hypomethylating agents (HMAs) represent a substantial potential boon for patients with myelodysplastic syndrome (MDS) who have previously required between 5 and 7 visits per month to an infusion clinic to receive therapy. For patients who respond to treatment, ongoing monthly maintenance visits represent a considerable burden to quality of life, and for those who are early in therapy, these sequential visits may tax transportation and financial resources that would be optimally distributed over the treatment cycle to facilitate transfusion support. The availability of oral HMAs may support the optimal application of these agents by contributing to adherence and lessening the burden of therapy, potentially encouraging patients to stay on longer-term treatment. Distinct pharmacokinetic profiles for the recently approved oral HMAs (oral azacitidine and decitabine-cedazuridine) result in differential toxicity profiles and have prompted their clinical trial development in lower- and higher-risk MDS, respectively.

Graphical abstract

Figure 1.

Chemical structure of cytidine, azacitidine analogues, and the breakdown products of CDA.

Figure 2.

Concentration time curves for (a) IV decitabine vs oral C-DEC and (b) SQ azacitidine vs CC-486.^, Figure 2a was reproduced from Future Oncol. 2021;17(16):2077-2087 and was modified only by renumbering for the purpose of this article. Figure 2b was reproduced from Leukemia 2016;30(4):889-896 and was also modified only by renumbering. Both works are licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. http://creativecommons.org/licenses/by-nc-nd/4.0/

Figure 3.

Summary comparison of the 2 completed phase 3 studies of C-DEC and CC-486 in MDS. Data abstracted from Garcia-Manero et al^,, and Savona et al. AZA, azacitidine; DAC, decitabine.