Upadhyay Banskota Shristi, Khanal Nabin, Marar Rosalyn I, Dhakal Prajwal, Bhatt Vijaya Raj
Division of Hematology and Oncology, University of Nebraska Medical Center, Omaha, NE, USA.
Division of Hematology and Oncology, Franciscan Health, Indianapolis, IN, USA.
Curr Hematol Malig Rep. 2022 Dec;17(6):217-227. doi: 10.1007/s11899-022-00674-4. Epub 2022 Aug 16.
We review how understanding the fitness and comorbidity burden of patients, and molecular landscape of underlying acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) at the time of diagnosis is now integral to treatment.
The upfront identification of patients' fitness and molecular profile facilitates selection of targeted and novel agents, enables risk stratification, allows consideration of allogeneic hematopoietic cell transplantation in high-risk patients, and provides treatment selection for older (age ≥ 75) or otherwise unfit patients who may not tolerate conventional treatment. The use of measurable residual disease (MRD) assessment improves outcome prediction and can also guide therapeutic strategies such as chemotherapy maintenance and transplant. In recent years, several novel drugs have received FDA approval for treating patients with AML with or without specific mutations. A doublet and triplet combination of molecular targeted and other novel treatments have resulted in high response rates in early trials. Following the initial success in AML, novel drugs are undergoing clinical trials in MDS. Unprecedented advances have been made in precision medicine approaches in AML and MDS. However, lack of durable responses and long-term disease control in many patients still present significant challenges, which can only be met, to some extent, with innovative combination strategies throughout the course of treatment from induction to consolidation and maintenance.
我们回顾了了解患者的健康状况和合并症负担，以及诊断时潜在急性髓系白血病（AML）和骨髓增生异常综合征（MDS）的分子格局如何成为治疗的重要组成部分。
对患者健康状况和分子特征的早期识别有助于选择靶向和新型药物，实现风险分层，考虑高危患者进行异基因造血细胞移植，并为可能无法耐受传统治疗的老年（年龄≥75岁）或其他身体状况不佳的患者提供治疗选择。可测量残留病（MRD）评估的使用改善了预后预测，还可指导化疗维持和移植等治疗策略。近年来，几种新型药物已获得FDA批准用于治疗有或无特定突变的AML患者。分子靶向治疗和其他新型治疗的双联和三联组合在早期试验中取得了高缓解率。继AML取得初步成功后，新型药物正在MDS中进行临床试验。AML和MDS的精准医学方法取得了前所未有的进展。然而，许多患者缺乏持久缓解和长期疾病控制仍然是重大挑战，只有通过从诱导到巩固和维持的整个治疗过程中的创新联合策略才能在一定程度上应对这些挑战。
