Incidence and management of CAR-T neurotoxicity in patients with multiple myeloma treated with ciltacabtagene autoleucel in CARTITUDE studies.
Incidence and management of CAR-T neurotoxicity in patients with multiple myeloma treated with ciltacabtagene autoleucel in CARTITUDE studies.
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DOI：
10.1038/s41408-022-00629-1
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发表时间：
2022-02-24
影响因子：
12.8
通讯作者：
Jagannath S
中科院分区：
文献类型：
--
作者：
Cohen AD;Parekh S;Santomasso BD;Gállego Pérez-Larraya J;van de Donk NWCJ;Arnulf B;Mateos MV;Lendvai N;Jackson CC;De Braganca KC;Schecter JM;Marquez L;Lee E;Cornax I;Zudaire E;Li C;Olyslager Y;Madduri D;Varsos H;Pacaud L;Akram M;Geng D;Jakubowiak A;Einsele H;Jagannath S
嵌合抗原受体（CAR） t细胞疗法对多发性骨髓瘤（MM）非常有效，但在一些患者中，其令人印象深刻的疗效与治疗相关的神经毒性有关。在cartitute -1中，5%的MM患者报告了使用ciltacabtagene autoeucel (cilta-cel)（一种b细胞成熟抗原靶向CAR -t细胞疗法）治疗时出现的运动和神经认知不良事件（MNTs）。我们在cartitde -1中评估了mnt的相关因素。基于共同特征，经历mnt的患者的特征是存在至少两个变量的组合：高肿瘤负担，cilta细胞输注后≥2级细胞因子释放综合征（CRS）或任何级别免疫效应细胞相关神经毒性综合征（ICANS），以及高CAR - t细胞扩增/持久性。在cilta-细胞开发项目中实施了监测和管理MNTs患者的策略，包括增强桥接治疗以减少基线肿瘤负担，早期积极治疗CRS和ICANS，早期症状检测的手写评估，以及延长输注后100天以上的神经毒性监测/报告时间。在成功实施这些策略后，在cilta- cell项目中，mnt的发病率从5%降至<1%，支持其治疗MM的有利收益-风险特征。
Chimeric antigen receptor (CAR) T-cell therapies are highly effective for multiple myeloma (MM) but their impressive efficacy is associated with treatment-related neurotoxicities in some patients. In CARTITUDE-1, 5% of patients with MM reported movement and neurocognitive treatment-emergent adverse events (MNTs) with ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen-targeted CAR T-cell therapy. We assessed the associated factors for MNTs in CARTITUDE-1. Based on common features, patients who experienced MNTs were characterized by the presence of a combination of at least two variables: high tumor burden, grade ≥2 cytokine release syndrome (CRS) or any grade immune effector cell-associated neurotoxicity syndrome (ICANS) after cilta-cel infusion, and high CAR T-cell expansion/persistence. Strategies were implemented across the cilta-cel development program to monitor and manage patients with MNTs, including enhanced bridging therapy to reduce baseline tumor burden, early aggressive treatment of CRS and ICANS, handwriting assessments for early symptom detection, and extended monitoring/reporting time for neurotoxicity beyond 100 days post-infusion. After successful implementation of these strategies, the incidence of MNTs was reduced from 5% to <1% across the cilta-cel program, supporting its favorable benefit–risk profile for treatment of MM.
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影响因子：
28.2
作者：
Gust J;Hay KA;Hanafi LA;Li D;Myerson D;Gonzalez-Cuyar LF;Yeung C;Liles WC;Wurfel M;Lopez JA;Chen J;Chung D;Harju-Baker S;Özpolat T;Fink KR;Riddell SR;Maloney DG;Turtle CJ
通讯作者：
Turtle CJ
DOI：
10.1056/nejmoa1707447
发表时间：
2017-12-28
期刊：
The New England journal of medicine
影响因子：
--
作者：
Neelapu SS;Locke FL;Bartlett NL;Lekakis LJ;Miklos DB;Jacobson CA;Braunschweig I;Oluwole OO;Siddiqi T;Lin Y;Timmerman JM;Stiff PJ;Friedberg JW;Flinn IW;Goy A;Hill BT;Smith MR;Deol A;Farooq U;McSweeney P;Munoz J;Avivi I;Castro JE;Westin JR;Chavez JC;Ghobadi A;Komanduri KV;Levy R;Jacobsen ED;Witzig TE;Reagan P;Bot A;Rossi J;Navale L;Jiang Y;Aycock J;Elias M;Chang D;Wiezorek J;Go WY
通讯作者：
Go WY
DOI：
10.1038/nrclinonc.2017.148
发表时间：
2018-01
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
Neelapu SS;Tummala S;Kebriaei P;Wierda W;Gutierrez C;Locke FL;Komanduri KV;Lin Y;Jain N;Daver N;Westin J;Gulbis AM;Loghin ME;de Groot JF;Adkins S;Davis SE;Rezvani K;Hwu P;Shpall EJ
通讯作者：
Shpall EJ
影响因子：
11.2
作者：
通讯作者：
--
影响因子：
158.5
作者：
Schuster, Stephen J.;Bishop, Michael R.;Maziarz, Richard T.
通讯作者：
Maziarz, Richard T.