CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Primary vs. pre-emptive anti-seizure medication prophylaxis in anti-CD19 CAR T-cell therapy.
Primary vs. pre-emptive anti-seizure medication prophylaxis in anti-CD19 CAR T-cell therapy.
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我们的数据表明,一级预防和抢先抗癫痫预防在抗 CD19 CAR-T 细胞治疗受者中均安全有效。
纳入连续接受抗CD19 CAR-T 治疗的难治性非霍奇金淋巴瘤患者,按相似内部方案筛选和评估。ASM可在CAR-T 输注前作为一级预防用药(PP组),或仅在出现神经毒性时作为抢先治疗(PET组)。
共纳入156例患者(PP组88例,PET组66例)。总体神经毒性和重度神经毒性分别见于45例(29%)和20例(13%),两组分布相近。5例患者发生癫痫事件(PET组3例,4%;PP组2例,2%)。PET组的癫痫/癫痫持续状态均在未出现明显CAR-T 相关神经毒性的情况下发生;PP组则仅有患者在严重神经毒性伴进行性重度脑病背景下出现短暂癫痫。所有患者均良好耐受ASM,即使未进行剂量滴定亦如此。无人发展为癫痫,也无人需要长期使用ASM。
数据显示,抗CD19 CAR-T 受者采用一级预防或抢先抗癫痫预防均安全有效。临床理由提示一级预防可能更有利,但本研究无法明确判定两种策略何者更优。
Consecutive patients affected by refractory non-Hodgkin lymphoma who received anti-CD19 CAR T-cells were included. Patients were selected and assessed using similar internal protocols. ASM was started either as a primary prophylaxis (PP-group) before CAR T-cells infusion or as a pre-emptive therapy (PET-group) only upon the onset of neurotoxicity development.
One hundred fifty-six patients were included (PP-group = 88, PET-group = 66). Overall, neurotoxicity and severe neurotoxicity occurred in 45 (29%) and 20 (13%) patients, respectively, equally distributed between the two groups. Five patients experienced epileptic events (PET-group = 3 [4%]; PP-group = 2 [2%]). For all the PET-group patients, seizure/status epilepticus occurred in the absence of overt CAR-T-related neurotoxicity, whereas patients in the PP-group experienced brief seizures only in the context of critical neurotoxicity with progressive severe encephalopathy. ASMs were well-tolerated by all patients, even without titration. No patients developed epilepsy or required long-term ASMs.
Our data suggest that both primary and pre-emptive anti-seizure prophylaxis are safe and effective in anti-CD19 CAR T-cell recipients. Clinical rationale suggests a possible more favourable profile of primary prophylaxis, yet no definitive conclusion of superiority between the two ASM strategies can be drawn from our study.
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