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:Role of Pulmonary Function Tests to Predict Complications After Chimeric Antigen Receptor T-Cell Therapy.
Role of Pulmonary Function Tests to Predict Complications After Chimeric Antigen Receptor T-Cell Therapy.
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CAR-T 治疗前肺量计检查与 cDLCO 联合应用可能有助于临床医生了解 CAR-T 细胞治疗后毒性的风险。
CAR-T 细胞疗法(CAR-T)已改变了某些血液系统恶性肿瘤的治疗,但毒性反应限制了其疗效。CAR-T 前肺功能检测(PFT)在预测毒性反应中的作用尚不明确。
我们的目的是探讨在CAR-T 治疗前获得的PFT与淋巴瘤患者后续并发症之间的关联。
我们开展了一项回顾性研究,纳入在本机构接受标准治疗CAR-T 且治疗前有PFTs的患者。使用全球肺倡议组织的种族中立规范方程生成肺量计和一氧化碳弥散量(DLCO)的预测值百分比(PPV)。肺功能评分(LFS)通过将第一秒用力呼气容积(FEV 1)和经血红蛋白水平校正的一氧化碳肺弥散量(cDLCO)以等权重方式合并计算,评分越高表示肺功能越差。使用二元logistic回归模型比较PFTs与CAR-T 后并发症的关联。另外拟合Cox回归模型以识别死亡率的预测因素。
在218例接受CAR-T 治疗的患者中,66例在淋巴细胞清除前12个月内进行了PFTs。在调整治疗线数后,较高的LFS与较高的CRS风险相关(OR 4.3,95% CI,1.4-29,P = .048)。在调整治疗线数后,FEV 1(OR = 0.96,95% CI,0.93-0.99,P = .05)和FVC(OR = 0.96,95% CI 0.92-0.99,P = .03)均对ICANS具有保护作用。PFT异常与早期或晚期死亡率无关。
Chimeric antigen receptor T-cell therapy (CAR-T) has transformed the treatment of certain hematologic malignancies, but toxicities limit efficacy. The role of pre-CAR-T pulmonary function testing (PFT) to predict toxicities is unclear.
Our aim was to examine the association between PFTs obtained prior to CAR-T and subsequent complications in patients with lymphoma. STUDY DESIGN: We conducted a retrospective study of patients who underwent standard-of-care CAR-T at our institution with pretherapy PFTs. Race-neutral normative equations from the Global Lung Initiative were used to generate percent-predicted values (PPV) for spirometry and diffusing capacity of the lungs for carbon monoxide (DLCO). Lung function score (LFS) was calculated by combining the forced expiratory volume in the first second (FEV 1 ) and the diffusion capacity of the lung for carbon monoxide corrected for hemoglobin level (cDLCO) in an equally distributed manner, with higher score denoting worse lung function. Binary logistic regression models were used to compare the association of PFTs with complications after CAR-T. Cox regression models were additionally fit to identify predictors of mortality.
Of 218 individuals who underwent CAR-T therapy, 66 had PFTs performed within 12 months prior to lymphodepletion. Higher LFS was associated with higher risk of CRS (OR 4.3, 95% CI, 1.4-29, P = .048), after adjusting for lines of treatment. When adjusting for lines of treatment, both FEV 1 (OR = 0.96, 95% CI, 0.93-0.99, P = .05) and FVC (OR = 0.96, 95% CI 0.92-0.99, P = .03) are protective for ICANS. PFT abnormalities were not associated with early or late mortality.
The combination of pre-CAR-T spirometry and cDLCO may help clinicians understand the risk for toxicities after CAR-T cell therapy.
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