Division of Hematology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA.
Section of Hematology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA.
Expert Rev Anticancer Ther. 2023 Jul-Dec;23(9):903-911. doi: 10.1080/14737140.2023.2238897. Epub 2023 Jul 20.
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.
患有骨髓增生性肿瘤（如骨髓增生异常/肿瘤（MDS）和急性髓系白血病（AML））的患者通常年龄较大，许多患者不符合治愈性强化治疗和/或异基因造血干细胞移植的条件。虽然强度较低的基于低甲基化剂（HMA）的治疗方法，如阿扎胞苷+维奈克拉，显著改善了患者的预后，但反应并不持久，大多数患者死于与疾病相关的并发症。口服 HMA（如 Cedazuridine-Decitabine [C-DEC] 和口服阿扎胞苷 [CC-486]）的批准燃起了希望，即髓系恶性肿瘤可能很快可以通过全口服治疗来治疗。
我们回顾了所有口服治疗方法，包括 C-DEC 和 CC-486 在 MDS 和 AML 中的分别批准，以及在高危（HR）MDS 和 AML 中出现的新兴口服单药和联合治疗方法。
口服 HMA 有可能成为 HR-MDS 或 AML 患者的一种方便且疗效相当的治疗选择，通过减少药物管理的就诊次数来提高患者的生活质量。全口服治疗联合方案，主要包括口服 HMA“骨干”，目前处于临床开发的早期阶段，我们希望这些药物的精心设计的试验能够尽快确定最佳方案，从而提供有效、耐受性良好的疾病导向治疗。
