Use, Access, and Initial Outcomes of Off-Label Ivosidenib in Patients with IDH1 Mutant Glioma

IF 2.4 Q2 CLINICAL NEUROLOGY
Katherine B Peters, Candice Alford, Amy Heltemes, Alicia Savelli, Daniel B Landi, Gloria Broadwater, Annick Desjardins, Margaret O Johnson, Justin T Low, Mustafa Khasraw, David M Ashley, Henry S Friedman, Mallika P Patel
{"title":"Use, Access, and Initial Outcomes of Off-Label Ivosidenib in Patients with IDH1 Mutant Glioma","authors":"Katherine B Peters, Candice Alford, Amy Heltemes, Alicia Savelli, Daniel B Landi, Gloria Broadwater, Annick Desjardins, Margaret O Johnson, Justin T Low, Mustafa Khasraw, David M Ashley, Henry S Friedman, Mallika P Patel","doi":"10.1093/nop/npad068","DOIUrl":null,"url":null,"abstract":"Abstract Background Isocitrate dehydrogenase (IDH) is commonly mutated (mIDH) in gliomas, and this mutant enzyme produces the oncometabolite 2-hydroxyglutarate (2HG). 2HG promotes gliomagenesis and is implicated in epileptogenesis. Ivosidenib (IVO), a small molecule oral mIDH1 inhibitor, is FDA-approved for mIDH1 newly diagnosed and relapsed/refractory acute myeloid leukemia. Moreover, IVO has efficacy in clinical trials for recurrent mIDH1 gliomas. Given the lack of targeted treatments for gliomas, we initiated off-label IVO for mIDH glioma patients in October 2020. Methods Retrospectively, we sought to assess early outcomes in our patients and describe their experience on IVO from October 2020 through February 2022. Our objective was to report on the following variables of off-label use of IVO: radiographic response, seizure control, tolerability, and access to the medication. All patients initially received single-agent IVO dosed at 500 mg orally once daily. Results The cohort age range was 21–74 years. Tumor types included astrocytoma (n = 14) and oligodendroglioma (n = 16), with most being grade 2 (n = 21). The best radiographic response in nonenhancing disease (n = 22) was 12 stable diseases, 5 minor responses, 3 partial responses, and 2 progressive diseases. Seizure frequency was stable to improved for most patients (70%, n = 21). IVO was well-tolerated, with the most common toxicities being diarrhea, elevated creatine kinase, and QTc interval prolongation. Most patients (66.7%, n = 20) received drugs via the patient assistance program, with insurance initially covering a third of patients and with ongoing use, later covering 60%. Conclusions Targeted therapies like IVO are options for mIDH glioma patients and can provide positive oncologic and neurological outcomes.","PeriodicalId":19234,"journal":{"name":"Neuro-oncology practice","volume":"6 1","pages":"0"},"PeriodicalIF":2.4000,"publicationDate":"2023-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuro-oncology practice","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1093/nop/npad068","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Abstract Background Isocitrate dehydrogenase (IDH) is commonly mutated (mIDH) in gliomas, and this mutant enzyme produces the oncometabolite 2-hydroxyglutarate (2HG). 2HG promotes gliomagenesis and is implicated in epileptogenesis. Ivosidenib (IVO), a small molecule oral mIDH1 inhibitor, is FDA-approved for mIDH1 newly diagnosed and relapsed/refractory acute myeloid leukemia. Moreover, IVO has efficacy in clinical trials for recurrent mIDH1 gliomas. Given the lack of targeted treatments for gliomas, we initiated off-label IVO for mIDH glioma patients in October 2020. Methods Retrospectively, we sought to assess early outcomes in our patients and describe their experience on IVO from October 2020 through February 2022. Our objective was to report on the following variables of off-label use of IVO: radiographic response, seizure control, tolerability, and access to the medication. All patients initially received single-agent IVO dosed at 500 mg orally once daily. Results The cohort age range was 21–74 years. Tumor types included astrocytoma (n = 14) and oligodendroglioma (n = 16), with most being grade 2 (n = 21). The best radiographic response in nonenhancing disease (n = 22) was 12 stable diseases, 5 minor responses, 3 partial responses, and 2 progressive diseases. Seizure frequency was stable to improved for most patients (70%, n = 21). IVO was well-tolerated, with the most common toxicities being diarrhea, elevated creatine kinase, and QTc interval prolongation. Most patients (66.7%, n = 20) received drugs via the patient assistance program, with insurance initially covering a third of patients and with ongoing use, later covering 60%. Conclusions Targeted therapies like IVO are options for mIDH glioma patients and can provide positive oncologic and neurological outcomes.
Ivosidenib在IDH1突变型胶质瘤患者中的使用、获取和初步结果
背景异柠檬酸脱氢酶(IDH)在胶质瘤中通常发生突变(mIDH),这种突变酶产生肿瘤代谢物2-羟基戊二酸(2HG)。2HG促进胶质瘤形成,并与癫痫发生有关。Ivosidenib (IVO)是一种小分子口服mIDH1抑制剂,已获fda批准用于治疗mIDH1新诊断和复发/难治性急性髓性白血病。此外,IVO在临床试验中对复发性mIDH1胶质瘤有疗效。鉴于缺乏针对胶质瘤的靶向治疗,我们于2020年10月启动了mIDH胶质瘤患者的标签外IVO。方法回顾性地评估患者的早期结局,并描述他们在2020年10月至2022年2月期间进行IVO的经历。我们的目的是报告IVO说明书外使用的以下变量:影像学反应、癫痫控制、耐受性和药物的可及性。所有患者最初均接受单药IVO治疗,剂量为500mg,每日口服一次。结果队列年龄21 ~ 74岁。肿瘤类型包括星形细胞瘤(n = 14)和少突胶质细胞瘤(n = 16),其中大多数为2级(n = 21)。非增强性疾病的最佳x线反应(n = 22)为稳定疾病12例,轻微反应5例,部分反应3例,进展性疾病2例。大多数患者的癫痫发作频率稳定或改善(70%,n = 21)。IVO耐受性良好,最常见的毒性是腹泻、肌酸激酶升高和QTc间期延长。大多数患者(66.7%,n = 20)通过患者援助计划获得药物,保险最初覆盖三分之一的患者,持续使用,后来覆盖60%。结论IVO等靶向治疗是mIDH胶质瘤患者的选择,可以提供积极的肿瘤学和神经学结果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Neuro-oncology practice
Neuro-oncology practice CLINICAL NEUROLOGY-
CiteScore
5.30
自引率
11.10%
发文量
92
期刊介绍: Neuro-Oncology Practice focuses on the clinical aspects of the subspecialty for practicing clinicians and healthcare specialists from a variety of disciplines including physicians, nurses, physical/occupational therapists, neuropsychologists, and palliative care specialists, who have focused their careers on clinical patient care and who want to apply the latest treatment advances to their practice. These include: Applying new trial results to improve standards of patient care Translating scientific advances such as tumor molecular profiling and advanced imaging into clinical treatment decision making and personalized brain tumor therapies Raising awareness of basic, translational and clinical research in areas of symptom management, survivorship, neurocognitive function, end of life issues and caregiving
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信