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.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Dynamic risk stratification using early CAR-T expansion in R/R LBCL treated with axicabtagene ciloleucel.
Dynamic risk stratification using early CAR-T expansion in R/R LBCL treated with axicabtagene ciloleucel.
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输注后常规监测嵌合抗原受体(CAR)T细胞扩增的临床价值仍存在争议。我们对一个前瞻性收集的队列进行了回顾性分析,该队列包含176例接受axicabtagene ciloleucel(axi-cel)治疗的复发/难治性大B细胞淋巴瘤(LBCL)患者。在输注后第7、14和28天通过流式细胞术检测CAR-T 细胞扩增,其中111例患者进行了实时报告至临床服务部门。
我们分析了CAR-T 细胞扩增与疗效(无进展生存期[PFS])、毒性(细胞因子释放综合征[CRS]和免疫效应细胞相关神经毒性综合征[ICANS])及毒性管理之间的关联,并校正了基线危险因素。一个将第7天扩增与淋巴细胞清除前乳酸脱氢酶(LDH)及桥接治疗反应相结合的多变量模型显示,强劲的第7天扩增(48个细胞/ L)与PFS改善独立相关(风险比[HR],0.43;95%置信区间[CI] 0.22-0.83;p = 0.01)。较高的第7天扩增与CRS严重程度增加和ICANS发生率升高相关。较高的皮质类固醇暴露反映了这一毒性负担,但与PFS较差无关。
因此,将定量CAR-T 细胞计数纳入临床实践可能动态优化输注后的风险分层,并指导个体化管理,例如在有效后续治疗时代监测疾病进展的频率。
The clinical utility of routine monitoring of chimeric antigen receptor (CAR) T-cell expansion post-infusion remains controversial.
We conducted a retrospective analysis of a prospectively collected cohort of 176 patients with relapsed/refractory large B-cell lymphoma (LBCL) treated with axicabtagene ciloleucel (axi-cel). CAR T-cell expansion was measured by flow cytometry at days 7, 14 and 28 following infusion with real-time reporting to the clinical service in 111 patients.
We examined the association between CAR T-cell expansion, efficacy (progression-free survival [PFS]), toxicity (cytokine release syndrome [CRS] and immune effector cell-associated neurotoxicity syndrome [ICANS]) and toxicity management, accounting for baseline risk factors.
A multivariable model combining day 7 expansion with pre-lymphodepletion lactate dehydrogenase (LDH) and bridging response demonstrated that robust day 7 expansion ( 48 cells/ L) was independently associated with improved PFS (hazard ratio [HR], 0. 43; 95% confidence interval [CI] 0. 22-0. 83; p = 0. 01). Higher day 7 expansion was associated with increased CRS severity and ICANS incidence. Higher corticosteroid exposure reflected this toxicity burden but was not associated with inferior PFS.
Thus, incorporating quantitative CAR-T enumeration into clinical practice may dynamically refine risk stratification post-infusion and guide individualised management, such as the frequency of monitoring for progressive disease in the era of effective subsequent therapies.
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