IDH1-mutated relapsed or refractory AML: current challenges and future prospects

IF 3.9 Q2 ONCOLOGY

Blood and Lymphatic Cancer-Targets and Therapy Pub Date : 2019-06-01 DOI:10.2147/BLCTT.S177913

J. Megías-Vericat, O. Ballesta-López, E. Barragán, P. Montesinos

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引用次数: 21

Abstract

Abstract The prognosis of patients with relapsed or refractory acute myeloid leukemia (R/R AML) is discouraging with salvage standard approaches. Mutations of isocitrate dehydrogenase 1 (IDH1mut), present in 7–14% of AML patients, have been discovered recently, opening the door to targeted agents aiming to improve the outcomes in this setting. Several oral selective IDH1mut inhibitors are under investigation, ivosidenib being the first approved for R/R AML. We performed a systematic review to analyze the clinical outcomes and safety reported with IDH1mut inhibitors and other agents in adult patients with IDH1mut R/R AML. Ivosidenib in monotherapy achieved complete remission (CR) of 24%, overall response of 42%, and median overall survival of 9 months in R/R AML, and promising outcomes were reported with IDH305 and FT-2102. IDH1mut inhibitors were generally well tolerated, but some therapy-related toxicities should be monitored, including IDH-differentiation syndrome, prolongation of the QT interval, and leukocytosis, all manageable and reversible. Also, venetoclax, CB-839, PARP inhibitors, and IDH1 peptide vaccine are being studied in IDH1mut AML. The results of the ongoing and upcoming clinical trials will bring new evidence to establish the role of IDH1mut inhibitors in therapeutic strategies of AML.

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idh1突变的复发或难治性AML:当前挑战和未来前景

复发或难治性急性髓性白血病(R/R AML)患者的预后令人沮丧。最近在7-14%的AML患者中发现了异柠檬酸脱氢酶1 (IDH1mut)突变，这为靶向药物改善这种情况的结果打开了大门。几种口服选择性IDH1mut抑制剂正在研究中，ivosidenib是第一个被批准用于R/R AML的药物。我们进行了一项系统综述，分析IDH1mut抑制剂和其他药物治疗IDH1mut R/R AML成人患者的临床结果和安全性。Ivosidenib单药治疗R/R AML的完全缓解(CR)为24%，总缓解率为42%，中位总生存期为9个月，IDH305和FT-2102的结果令人鼓舞。IDH1mut抑制剂通常耐受性良好，但应监测一些与治疗相关的毒性，包括idh分化综合征、QT间期延长和白细胞增多症，这些都是可控和可逆的。此外，venetoclax、CB-839、PARP抑制剂和IDH1肽疫苗正在IDH1mut AML中进行研究。正在进行和即将进行的临床试验的结果将为确定IDH1mut抑制剂在AML治疗策略中的作用提供新的证据。

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

Blood and Lymphatic Cancer-Targets and Therapy ONCOLOGY-

自引率

7.10%

发文量

审稿时长

16 weeks

期刊介绍： Blood and Lymphatic Cancer: Targets and Therapy is an international, peer reviewed, open access journal focusing on blood and lymphatic cancer research, identification of therapeutic targets, and the optimal use of preventative and integrated treatment interventions to achieve improved outcomes, enhanced survival, and quality of life for the cancer patient. Specific topics covered in the journal include: Epidemiology, detection and screening Cellular research and biomarkers Identification of biotargets and agents with novel mechanisms of action Optimal clinical use of existing anticancer agents, including combination therapies Radiation, surgery, bone marrow transplantation Palliative care Patient adherence, quality of life, satisfaction Health economic evaluations.