Background/Objectives: Mutant isocitrate dehydrogenase (IDH) inhibitors represent a major advance in precision oncology. The recent Food and Drug Administration approval of vorasidenib for IDH-mutant glioma highlights its therapeutic potential in this setting. As this and other mutant IDH inhibitors enter the clinical setting, providers are tasked with staying informed of the evolving therapeutic landscape as more is learned about this unique class of medications. We aimed to summarize insights from preclinical studies and clinical trials exploring their use in IDH-mutant glioma.Methods: We reviewed notable preclinical studies establishing the rationale for targeting mutant IDH. We performed a systematic review of clincaltrials.gov to identify both completed and ongoing interventional IDH-directed trials in patients with IDH-mutant glioma.Results: We identified 8 published and 15 ongoing clinical trials evaluating IDH-directed therapies. IDH inhibitors have been shown to slow and, in some cases, reverse glioma tumor growth, with activity that may extend beyond their currently approved indications. The presence of contrast enhancement is consistently a negative predictor of response for ivosidenib and vorasidenib, although safusidenib and olutasidenib preliminarily may retain efficacy in these cases. Novel approaches such as IDH-directed vaccines and combination therapy using mutant IDH inhibitors with immunotherapy are currently under active investigation.Conclusions: Mutant IDH inhibition is a promising, well-tolerated, and evolving approach for many patients with IDH-mutant glioma. Ongoing research will clarify its optimal clinical utility and potentially expand its indication.
背景/目的：突变型异柠檬酸脱氢酶（IDH）抑制剂代表了精准肿瘤学领域的重大进展。美国食品药品监督管理局近期批准伏拉西地尼用于IDH突变型胶质瘤治疗，凸显了其在该领域的治疗潜力。随着此类及其他突变型IDH抑制剂进入临床应用，医疗从业者需要持续关注这类独特药物的最新研究进展和治疗格局变化。本研究旨在总结IDH突变型胶质瘤治疗中突变型IDH抑制剂的临床前研究及临床试验进展。 方法：我们回顾了奠定突变型IDH靶向治疗理论基础的重要临床前研究，并通过系统检索ClinicalTrials.gov数据库，识别已完成和正在进行的IDH突变型胶质瘤患者靶向干预试验。 结果：共发现8项已发表和15项正在进行的IDH靶向治疗临床试验。研究显示IDH抑制剂能延缓甚至逆转胶质瘤生长，其活性可能超越当前已批准的适应症范围。尽管增强显影的存在持续预示艾伏尼布和伏拉西地尼疗效不佳，但沙夫西地尼和奥卢他西地尼在这些病例中初步显示可能保留疗效。目前正在积极研究IDH靶向疫苗、突变型IDH抑制剂与免疫疗法联合治疗等新型治疗方案。 结论：对于众多IDH突变型胶质瘤患者而言，突变型IDH抑制是一种前景广阔、耐受性良好且不断发展的治疗策略。持续深入的研究将明确其最佳临床应用价值，并有望拓展其适应症范围。
Targeting of Mutant Isocitrate Dehydrogenase in Glioma: A Systematic Review
肿瘤(癌症)患者之家