新诊断急性髓系白血病不适合患者:2026治疗算法

IF 11.6 1区 医学 Q1 HEMATOLOGY
Naseema Gangat, Courtney D. Dinardo
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引用次数: 0

摘要

新诊断的急性髓性白血病(ND-AML)患者被认为不适合接受强化化疗的管理模式随着对疾病生物学的了解的提高而发展。在这种情况下,管理需要明确描述治疗目标,包括维持生活质量(QoL)。对于NPM1MUT或KMT2A重排(KMT2Ar)患者,venetoclax (Ven)和低甲基化剂(HMA)联合使用是目前大多数情况下的标准治疗,在药物剂量和治疗持续时间以及添加(三重组合)或替代靶向治疗(如FLT3、IDH1、IDH2或menin抑制剂)方面具有灵活的选择。Ven-HMA治疗后的缓解率(CR/CRi:40-90%)和总体生存结果(3年:0-67%)是高度可变的,主要取决于肿瘤遗传学,而实现完全缓解(CR)或没有计数恢复(CRi)和异体干细胞移植(ASCT)的巩固对于确保长期生存至关重要。对venhma应答有利的基因组预测因子包括NPM1MUT、IDH2MUT和DDX41MUT,不利的TP53MUT、FLT3-ITD和K/NRASMUT。有利的总生存预测因子包括IDH2MUT,不利的预测因子包括TP53MUT、FLT3-ITD、K/NRASMUT和KMT2Ar。三联方案是否在基因靶亚群中提供比Ven-HMA显著的生存增加仍有待确定。特别是那些被认为不适合进行vin - hma治疗的虚弱患者,可能会受益于针对FLT3MUT、IDH1/2MUT、npm1mut和KMT2Ar的单药治疗。未来的研究项目应侧重于在临床试验中纳入患者报告的结果,优化Ven-HMA的剂量和治疗时间,特别是在三联体组合中,扩大ASCT的使用并澄清其时间。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Newly diagnosed acute myeloid leukemia in unfit patients: 2026 treatment algorithms

Newly diagnosed acute myeloid leukemia in unfit patients: 2026 treatment algorithms

Management paradigms for newly-diagnosed acute myeloid leukemia (ND-AML) in patients considered unfit to receive intensive chemotherapy have evolved with improved understanding of disease biology. In this setting, management requires clear delineation of goals of therapy that should include preservation of quality-of-life (QoL). Combination of venetoclax (Ven) and a hypomethylating agent (HMA) is the current standard-of-care in most circumstances with flexible options in regard to drug dose and duration of treatment as well as the addition (triplet combinations) or alternative use of targeted therapies, such as inhibitors of FLT3, IDH1, IDH2, or menin for patients with NPM1MUT or KMT2A rearrangements (KMT2Ar). Response rates (CR/CRi:40-90%) and overall survival outcomes (3-year: 0–67%) following Ven-HMA therapy are highly variable and depend primarily on tumor genetics while achievement of complete response with (CR) or without count recovery (CRi) and consolidation with allogeneic stem cell transplant (ASCT) are essential in securing long-term survival. Favorable genomic predictors of response to Ven-HMA include NPM1MUT, IDH2MUT, and DDX41MUT, and unfavorable TP53MUT, FLT3-ITD, and K/NRASMUT. Favorable predictors of overall survival include IDH2MUT, and unfavorable TP53MUT, FLT3-ITD, K/NRASMUT, and KMT2Ar. Whether or not triplet regimens provide significant survival gain over Ven-HMA in genetically targetable subgroups remains to be determined. Particularly frail patients who are considered unfit for Ven-HMA might benefit from monotherapy targeting FLT3MUT, IDH1/2MUT, NPM1MUTor KMT2Ar. Future research projects should focus on incorporating patient-reported outcomes in clinical trials, optimization of Ven-HMA dosing and treatment duration especially in triplet combinations and broadening the use of ASCT and clarification of its timing.

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来源期刊
CiteScore
16.70
自引率
2.30%
发文量
153
审稿时长
>12 weeks
期刊介绍: Blood Cancer Journal is dedicated to publishing high-quality articles related to hematologic malignancies and related disorders. The journal welcomes submissions of original research, reviews, guidelines, and letters that are deemed to have a significant impact in the field. While the journal covers a wide range of topics, it particularly focuses on areas such as: Preclinical studies of new compounds, especially those that provide mechanistic insights Clinical trials and observations Reviews related to new drugs and current management of hematologic malignancies Novel observations related to new mutations, molecular pathways, and tumor genomics Blood Cancer Journal offers a forum for expedited publication of novel observations regarding new mutations or altered pathways.
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