Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
Curr Neurol Neurosci Rep. 2024 Dec;24(12):631-643. doi: 10.1007/s11910-024-01378-3. Epub 2024 Sep 20.
The identification of isocitrate dehydrogenase (IDH) mutations has led to a transformation in our understanding of gliomas and has paved the way to a new era of targeted therapy. In this article, we review the classification of IDH-mutant glioma, standard of care treatment options, clinical evidence for mutant IDH (mIDH) inhibitors, and practical implications of the recent landmark INDIGO trial.
In the phase 3 randomized placebo-controlled INDIGO trial, mIDH1/2 inhibitor vorasidenib increased progression-free survival among non-enhancing grade 2 IDH-mutant gliomas following surgery. This marks the first positive randomized trial of targeted therapy in IDH-mutant glioma, and led to the US Food and Drug Administration's approval of vorasidenib in August 2024 for grade 2 IDH-mutant glioma. Vorasidenib is a well-tolerated treatment that can benefit a subset of patients with IDH-mutant glioma. Targeting mIDH also remains a promising strategy for select groups of patients excluded from the INDIGO trial. Ongoing and future studies, including with new agents and with combination therapy approaches, may expand the benefit and unlock the potential of mIDH inhibitors.
异柠檬酸脱氢酶（IDH）突变的鉴定改变了我们对神经胶质瘤的认识，并为靶向治疗的新时代铺平了道路。本文回顾了 IDH 突变型神经胶质瘤的分类、标准治疗选择、突变型 IDH（mIDH）抑制剂的临床证据，以及最近具有里程碑意义的 INDIGO 试验的实际意义。
在 III 期随机安慰剂对照 INDIGO 试验中，mIDH1/2 抑制剂ivosidenib 增加了手术后非增强性 2 级 IDH 突变型神经胶质瘤的无进展生存期。这标志着 IDH 突变型神经胶质瘤靶向治疗的首次阳性随机试验，导致美国食品和药物管理局于 2024 年 8 月批准ivosidenib 用于 2 级 IDH 突变型神经胶质瘤。ivosidenib 是一种耐受性良好的治疗方法，可以使一部分 IDH 突变型神经胶质瘤患者受益。针对 mIDH 仍然是排除在 INDIGO 试验之外的特定患者群体的有前途的策略。正在进行和未来的研究，包括新药物和联合治疗方法，可能会扩大 mIDH 抑制剂的获益并挖掘其潜力。
