Garcia Catherine R, Highsmith Kaitlin, Knight Stephanie, Andrade Ivan Pradilla, Leung Cheuk Hong, Puduvalli Vinay, Kamiya-Matsuoka Carlos
Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Division of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
J Neurooncol. 2025 Nov;175(2):837-844. doi: 10.1007/s11060-025-05183-x. Epub 2025 Aug 1.
The role of IDH inhibitors in recurrent high-grade gliomas (HGG) is not well described. We present the outcomes of patients with HGG that were treated with these agents at our institution.
We reviewed patients with recurrent IDH-mutant HGG treated with FDA approved IDH inhibitors (ivosidenib, enasidenib, and vorasidenib) from December 2019 to December 2024 at the University of Texas MD Anderson Cancer Center.
23 patients were identified of which 65.2% were male. Tumors included astrocytoma (n = 14, 60.9%) and WHO grade 3 oligodendroglioma (n = 9, 39.1%), with four patients having a WHO grade 4 astrocytoma and 10 a WHO grade 3 astrocytoma. Twenty patients had enhancing disease at the time an IDH inhibitor was recommended. One patient was treated with enasidenib, 17 with ivosidenib, and 5 with vorasidenib. Of those initially treated with ivosidenib, 9 were switched to vorasidenib. Two patients discontinued the drugs due to side effects, that included elevated liver enzymes (n = 1), and diarrhea (n = 1). All patients had received prior surgery, radiation, and chemotherapy before starting an IDH inhibitor. Median overall survival (OS) was not reached. OS after IDH inhibitor was 20.7 months and was longer in patients that had not received initial chemotherapy (p = 0.032). Median progression-free survival (PFS) was 6.8 months and was not different between tumor type, sex, or number of recurrences, but was longer in patients that did not receive initial chemotherapy (p = 0.041).
IDH inhibitors were well tolerated in patients with IDH-mutant HGG previously treated with DNA-damaging agents. A median PFS longer than 6 months is encouraging in this patient population and may be due to antitumor activity of IDH inhibitors in recurrent HGG.
异柠檬酸脱氢酶（IDH）抑制剂在复发性高级别胶质瘤（HGG）中的作用尚未得到充分描述。我们介绍了在我们机构接受这些药物治疗的HGG患者的治疗结果。
我们回顾了2019年12月至2024年12月在德克萨斯大学MD安德森癌症中心接受FDA批准的IDH抑制剂（依维替尼、恩扎替尼和伏拉替尼）治疗的复发性IDH突变型HGG患者。
共确定了23例患者，其中65.2%为男性。肿瘤包括星形细胞瘤（n = 14，60.9%）和世界卫生组织3级少突胶质细胞瘤（n = 9，39.1%），4例为世界卫生组织4级星形细胞瘤，10例为世界卫生组织3级星形细胞瘤。在推荐使用IDH抑制剂时，20例患者有强化病灶。1例患者接受恩扎替尼治疗，17例接受依维替尼治疗，5例接受伏拉替尼治疗。在最初接受依维替尼治疗的患者中，9例改为伏拉替尼治疗。2例患者因副作用停药，包括肝酶升高（n = 1）和腹泻（n = 1）。所有患者在开始使用IDH抑制剂之前均接受过手术、放疗和化疗。总生存期（OS）未达到中位值。使用IDH抑制剂后的OS为20.7个月，未接受初始化疗的患者生存期更长（p = 0.032）。无进展生存期（PFS）的中位值为6.8个月，在肿瘤类型、性别或复发次数之间无差异，但未接受初始化疗的患者PFS更长（p = 0.041）。
IDH抑制剂在先前接受过DNA损伤剂治疗的IDH突变型HGG患者中耐受性良好。该患者群体中PFS中位值超过6个月令人鼓舞，这可能归因于IDH抑制剂在复发性HGG中的抗肿瘤活性。
