Ixazomib in addition to chemotherapy for the treatment of acute myeloid leukemia in older adults.

IF 2.2 4区医学 Q3 HEMATOLOGY Leukemia & Lymphoma Pub Date : 2025-07-01 Epub Date: 2025-03-12 DOI:10.1080/10428194.2025.2476655

Philip C Amrein, Frederic I Preffer, Geoffrey Fell, Eyal C Attar, Rupa Narayan, Traci M Blonquist, Andrew M Brunner, Gabriela S Hobbs, Hanno R Hock, Steven L McAfee, Jenna A Moran, Meghan K Bergeron, Julia E Foster, Christina Bertoli, Kristin McGregor, Christine Connolly, Tanya T Behnan, Tina T Som, Aura Y Ramos, Megan K Vartanian, Jennifer Lombardi Story, Donna S Neuberg, Amir T Fathi

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Abstract

Outcome for acute myeloid leukemia (AML) patients aged >60 years is poor. Targeting the proteasome in AML is attractive, since leukemia stem cells demonstrate sensitivity to proteasome inhibition in preclinical models. Adults >60 years of age with newly diagnosed AML were enrolled. Induction consisted of cytarabine and daunorubicin with ixazomib provided on days 2, 5, 9, and 12. In a second phase, induction was followed by consolidation with cytarabine and ixazomib on days 2, 5, 9, and 12. Among the 39 patients enrolled, there was 1 DLT, grade 4 thrombocytopenia. There were no grade 3 or 4 neurotoxicity events attributable to ixazomib. The composite remission rate (CCR) was 69%. The median OS for the 39 patients was 38.5 months. The highest dose level (3 mg) of ixazomib planned for induction and consolidation in this trial has been reached safely and is the RP2D for both.

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伊沙唑米在化疗之外用于治疗老年人急性髓性白血病。

急性髓性白血病（AML）患者的预后较差。在AML中靶向蛋白酶体是有吸引力的，因为白血病干细胞在临床前模型中表现出对蛋白酶体抑制的敏感性。研究对象为新诊断的AML患者，年龄在60岁至60岁之间。诱导包括阿糖胞苷和柔红霉素，伊唑唑米在第2、5、9和12天提供。在第二阶段，诱导后在第2、5、9和12天用阿糖胞苷和伊唑唑米巩固。在纳入的39例患者中，有1例DLT， 4级血小板减少症。ixazomib没有3级或4级神经毒性事件。综合缓解率（CCR）为69%。39例患者的中位OS为38.5个月。在本试验中，ixazomib计划用于诱导和巩固的最高剂量水平（3mg）已经安全达到，并且是RP2D。

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来源期刊

Leukemia & Lymphoma 医学-血液学

CiteScore

4.10

自引率

3.80%

发文量

384

审稿时长

1.8 months

期刊介绍： Leukemia & Lymphoma in its fourth decade continues to provide an international forum for publication of high quality clinical, translational, and basic science research, and original observations relating to all aspects of hematological malignancies. The scope ranges from clinical and clinico-pathological investigations to fundamental research in disease biology, mechanisms of action of novel agents, development of combination chemotherapy, pharmacology and pharmacogenomics as well as ethics and epidemiology. Submissions of unique clinical observations or confirmatory studies are considered and published as Letters to the Editor