Outcomes of Frontline Triplet Regimens With a Hypomethylating Agent, Venetoclax, and Isocitrate Dehydrogenase Inhibitor for Intensive Chemotherapy-Ineligible Patients With Isocitrate Dehydrogenase-Mutated AML.

IF 41.9 1区医学 Q1 ONCOLOGY

Journal of Clinical Oncology Pub Date : 2025-06-13 DOI:10.1200/JCO-25-00640

Courtney D DiNardo, Jennifer Marvin-Peek, Sanam Loghavi, Koichi Takahashi, Ghayas C Issa, Wei-Ying Jen, Naval G Daver, Patrick K Reville, Nicholas J Short, Koji Sasaki, Jillian K Mullin, Corey A Bradley, Gautam Borthakur, Abhishek Maiti, Yesid Alvarado, Naveen Pemmaraju, Hussein A Abbas, Danielle E Hammond, Fadi Haddad, Guillermo Montalban Bravo, Kelly S Chien, Musa Yilmaz, Steven M Kornblau, Elias Jabbour, Farhad Ravandi, Tapan Kadia, Guillermo Garcia-Manero, Marina Y Konopleva, Hagop M Kantarjian

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引用次数: 0

Abstract

Purpose: The development of targeted therapeutics has revolutionized treatment for elderly patients with AML. Two doublet regimens are approved in the frontline setting for intensive chemotherapy (IC)-ineligible AML: venetoclax (VEN) in combination with hypomethylating agent (HMA) therapy and azacitidine (AZA) plus ivosidenib (IVO) specifically for IDH1-mutated AML. Although both regimens have improved AML outcomes, most patients will either not respond to frontline therapy or relapse, with dismal salvage outcomes.

Methods: We herein report on 60 newly diagnosed IC-ineligible patients treated at our institution with triplet regimens for isocitrate dehydrogenase (IDH)-mutant AML. Patients received either AZA + VEN + IVO on NCT03471260 (IDH1-mutated patients only) or oral decitabine + VEN + IVO/enasidenib on NCT04774393 (arms for IDH1- and IDH2-mutant disease, respectively).

Results: The triplet regimens were well tolerated with low early mortality (n = 1 [2%] in 60 days) and a similar safety profile to HMA + VEN and isocitrate dehydrogenase inhibitor doublet regimens. The composite complete remission rate (CRc) was 92% (55/60), with an overall response rate of 95% (57/60). With a median follow-up of 27.4 months, the median overall survival (OS) has not yet been reached. The 2-year OS was 69% with a 2-year cumulative incidence of relapse of 24%. Patients with treated-secondary AML (tsAML) experienced inferior outcomes with a CRc of 71% (12/17) and a 2-year OS of 34%; the 2-year OS was 84% in patients without tsAML. Nineteen patients (32%) transitioned to stem cell transplant, and 51% remain on study.

Conclusion: Given the excellent outcomes of IDH-triplet therapy for newly diagnosed, IC-ineligible IDH-mutant AML, further prospective studies comparing IDH-triplet versus IDH-doublet regimens are warranted.

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低甲基化剂、Venetoclax和异柠檬酸脱氢酶抑制剂的一线三重方案治疗强化化疗不符合异柠檬酸脱氢酶突变AML患者的结果

目的：靶向治疗的发展彻底改变了老年AML患者的治疗。两种双重方案被批准用于强化化疗（IC）不符合条件的AML的一线设置：venetoclax （VEN）联合低甲基化剂（HMA）治疗和阿扎胞苷（AZA）加ivosidenib （IVO）特异性治疗idh1突变的AML。尽管这两种方案都改善了急性髓性白血病的预后，但大多数患者要么对一线治疗无反应，要么复发，挽回结果令人沮丧。方法：我们在此报告60例新诊断的ic不符合条件的患者在我们的机构接受三联体方案治疗异柠檬酸脱氢酶（IDH）突变的AML。患者接受AZA + VEN + IVO治疗NCT03471260（仅IDH1突变患者）或口服地西他滨+ VEN + IVO/enasidenib治疗NCT04774393（分别针对IDH1-和idh2突变疾病）。结果：三联方案耐受性良好，早期死亡率低（60天内n = 1[2%]），安全性与HMA + VEN和异柠檬酸脱氢酶抑制剂双联方案相似。复合完全缓解率（CRc）为92%(55/60)，总缓解率为95%（57/60）。中位随访期为27.4个月，中位总生存期（OS）尚未达到。2年总生存率为69%，2年累计复发率为24%。治疗后继发性AML （tsAML）患者的预后较差，CRc为71%(12/17)，2年OS为34%；无tsAML患者的2年OS为84%。19名患者（32%）转移到干细胞移植，51%仍在研究中。结论：考虑到idh -三胞胎治疗新诊断的、不符合ic条件的idh -突变型AML的良好结果，进一步的前瞻性研究比较idh -三胞胎和idh -双胞胎方案是有必要的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Clinical Oncology 医学-肿瘤学

CiteScore

41.20

自引率

2.20%

发文量

8215

审稿时长

2 months

期刊介绍： The Journal of Clinical Oncology serves its readers as the single most credible, authoritative resource for disseminating significant clinical oncology research. In print and in electronic format, JCO strives to publish the highest quality articles dedicated to clinical research. Original Reports remain the focus of JCO, but this scientific communication is enhanced by appropriately selected Editorials, Commentaries, Reviews, and other work that relate to the care of patients with cancer.