一线ivosidenib 对异柠檬酸脱氢酶突变型星形细胞瘤和少突胶质细胞瘤体积生长模式的影响。
Impact of Frontline Ivosidenib on Volumetric Growth Patterns in Isocitrate Dehydrogenase-mutant Astrocytic and Oligodendroglial Tumors.
机构信息
Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, School of Medicine, Baltimore, Maryland.
Department of Neurology, Johns Hopkins University, School of Medicine, Baltimore, Maryland.
出版信息
Clin Cancer Res. 2023 Dec 1;29(23):4863-4869. doi: 10.1158/1078-0432.CCR-23-0585.
PURPOSE
Isocitrate dehydrogenase (IDH)-mutant gliomas are usually treated with radiotherapy and chemotherapy, which increases the risk for neurocognitive sequelae during patients' most productive years. We report our experience using off-label first-in-class mutant IDH1 inhibitor ivosidenib and its impact on tumor volume in IDH-mutant gliomas.
EXPERIMENTAL DESIGN
We retrospectively analyzed patients ages ≥18 years with radiation/chemotherapy-naïve, mutant IDH1, nonenhancing, radiographically active, grade 2/3 gliomas, and ≥2 pretreatment and ≥2 on-treatment ivosidenib MRIs. T2/FLAIR-based tumor volumes, growth rates, and progression-free survival (PFS) were analyzed. log-linear mixed-effect modeling of growth curves adjusted for grade, histology, and age was performed.
RESULTS
We analyzed 116 MRIs of 12 patients [10 males, median age 46 years (range: 26-60)]: 8 astrocytomas (50% grade 3) and 4 grade 2 oligodendrogliomas. Median on-drug follow-up was 13.2 months [interquartile range (IQR): 9.7-22.2]. Tolerability was 100%. A total of 50% of patients experienced ≥20% tumor volume reduction on-treatment and absolute growth rate was lower during treatment (-1.2 ± 10.6 cc/year) than before treatment (8.0 ± 7.7 cc/year; P ≤ 0.05). log-linear models in the Stable group (n = 9) showed significant growth before treatment (53%/year; P = 0.013), and volume reduction (-34%/year; P = 0.037) after 5 months on treatment. After treatment, volume curves were significantly lower than before treatment (after/before treatment ratio 0.5; P < 0.01). Median time-to-best response was 11.2 (IQR: 1.7-33.4) months, and 16.8 (IQR: 2.6-33.5) months in patients on drug for ≥1 year. PFS at 9 months was 75%.
CONCLUSIONS
Ivosidenib was well tolerated and induced a high volumetric response rate. Responders had significant reduction in tumor growth rates and volume reductions observed after a 5-month delay. Thus, ivosidenib appears useful to control tumor growth and delay more toxic therapies in IDH-mutant nonenhancing indolently growing gliomas. See related commentary by Lukas and Horbinski, p. 4709.
目的
异柠檬酸脱氢酶（IDH）突变型胶质瘤通常采用放疗和化疗治疗，这会增加患者在最具生产力的年龄段出现神经认知后遗症的风险。我们报告了使用未经批准的首创新药 IDH1 突变抑制剂伊维替尼及其对 IDH 突变型胶质瘤肿瘤体积的影响。
实验设计
我们回顾性分析了年龄≥18 岁、未经放疗/化疗、突变 IDH1、非增强、影像学活跃、2/3 级胶质瘤、且至少有 2 次治疗前和≥2 次伊维替尼 MRI 的患者。分析 T2/FLAIR 为基础的肿瘤体积、增长率和无进展生存期（PFS）。对分级、组织学和年龄进行调整的生长曲线的对数线性混合效应模型进行了分析。
结果
我们分析了 12 名患者的 116 次 MRI [10 名男性，中位年龄 46 岁（范围：26-60）]：8 例星形细胞瘤（50%为 3 级）和 4 例 2 级少突胶质细胞瘤。中位药物治疗随访时间为 13.2 个月（四分位距[IQR]：9.7-22.2）。患者对药物的耐受性为 100%。共有 50%的患者在治疗过程中肿瘤体积减少≥20%，而治疗期间的绝对生长率（-1.2±10.6 cc/年）低于治疗前（8.0±7.7 cc/年；P≤0.05）。稳定组（n=9）的对数线性模型显示，治疗前有明显的生长（53%/年；P=0.013），治疗后 5 个月有明显的体积减少（-34%/年；P=0.037）。治疗后，体积曲线明显低于治疗前（治疗后/治疗前比值 0.5；P＜0.01）。最佳反应时间的中位数为 11.2（IQR：1.7-33.4）个月，治疗≥1 年的患者为 16.8（IQR：2.6-33.5）个月。9 个月时的 PFS 为 75%。
结论
伊维替尼耐受性良好，可诱导高体积缓解率。应答者的肿瘤生长率显著下降，且在 5 个月的延迟后观察到体积减少。因此，伊维替尼似乎可用于控制 IDH 突变型非增强性、惰性生长的胶质瘤的肿瘤生长并延迟更具毒性的治疗。见 Lukas 和 Horbinski 的相关评论，第 4709 页。
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