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:Factors associated with refractoriness or early progression after idecabtagene vicleucel in patients with relapsed/ refractory multiple myeloma: US Myeloma Immunotherapy Consortium real world experience.
Factors associated with refractoriness or early progression after idecabtagene vicleucel in patients with relapsed/ refractory multiple myeloma: US Myeloma Immunotherapy Consortium real world experience.
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伊德基奥仑赛(ide-cel)靶向B细胞成熟抗原(BCMA)的CAR-T 细胞治疗,对复发/难治性多发性骨髓瘤患者的缓解率和生存结局令人鼓舞,但仍有部分患者无应答或早期复发。了解这类患者的特征对于患者筛选和开发改善结局的新策略十分重要。
本研究评估美国11家学术中心接受标准治疗ide-cel患者发生早期进展(CAR-T 输注后3个月内骨髓瘤进展或相关死亡)的相关因素。211例接受ide-cel治疗的患者中,43例在输注后3个月内发生进展事件。既往有髓外病变、既往接受BCMA靶向治疗、淋巴细胞清除治疗时铁蛋白升高、接受桥接治疗、西班牙裔、浆细胞白血病及t(4;14)均与输注后3个月内进展风险较高相关(P<0.05)。单变量分析识别的风险因素中,既往髓外病变、既往BCMA靶向治疗、淋巴细胞清除时铁蛋白升高、浆细胞白血病和t(4;14)在多变量分析中均与较差无进展生存期(PFS)相关。上述因素中存在3项或以上会显著损害PFS(P<0.001;具有3项因素者中位PFS为3.2个月,无危险因素者为14.1个月)。
本研究有助于识别CAR-T 治疗后早期进展高风险患者;对此类患者在CAR-T 治疗前后采取针对性干预,可能改善结局。
While response rates and survival outcomes have been very promising for idecabtagene vicleucel (ide-cel), a proportion of patients do not respond or relapse early after this B-cell maturation antigen (BCMA) targeted chimeric antigen receptor (CAR) T-cell therapy. Understanding the characteristics of these patients is important for patient selection and development of novel strategies to improve outcomes.
We evaluated factors associated with early progression (progression or death due to myeloma 3 months after CAR T-cell infusion) in patients treated with standard of care ide-cel at 11 US academic centers. Among 211 patients that received ide-cel, 43 patients had a progressive event 3 months of infusion. Patients with a history of extramedullary disease, prior BCMA targeted therapy, elevated ferritin at lymphodepletion, use of bridging therapy, Hispanic ethnicity, plasma cell leukemia and t(4;14) were more likely to progress 3 months of infusion (P<0.
05). Of these risk factors for early progression identified in univariate analyses, history of extramedullary disease, prior BCMA targeted therapy, elevated ferritin at lymphodepletion, plasma cell leukemia, and t(4;14) were associated with worse progression-free survival (PFS) in multivariable analysis. Presence of three or more of these factors had a significant negative impact on PFS (P<0. 001; median PFS for 3 factors, 3. 2 months vs. 0 factors, 14. 1 months).
This study helps identify patients at high risk of early progression after CAR T-cell therapy who may benefit from specific interventions pre and post CAR T-cell therpy to improve outcomes.
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