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:Metabolic PET/CT analysis of aggressive Non-Hodgkin lymphoma prior to Axicabtagene Ciloleucel CAR-T infusion: predictors of progressive disease, survival, and toxicity.
Metabolic PET/CT analysis of aggressive Non-Hodgkin lymphoma prior to Axicabtagene Ciloleucel CAR-T infusion: predictors of progressive disease, survival, and toxicity.
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PET/CT 用于评估复发/难治性非霍奇金淋巴瘤(NHL)患者在CAR-T(CAR-T)细胞输注前的病情,检查时间点为白细胞单采前(pre-leuk)和淋巴细胞清除化疗前(pre-LD)。
我们假设,这两个时间点之间的 PET/CT 变化能够预测 CAR-T 治疗后的结局。研究对接受 axicabtagene ciloleucel 治疗的 NHL 患者,在 pre-leuk 和 pre-LD PET/CT 扫描中计算代谢肿瘤体积(MTV)、病灶总糖酵解(TLG)及其他指标,并分析其与治疗结局的关联。共分析 69 例患者。单一时间点的 PET/CT 特征与疾病进展(PD)或死亡风险无关;但从 pre-leuk 到 pre-LD,实质性 MTV、淋巴结 MTV、最大病灶 TLG 以及病灶总数增加,均与死亡风险升高相关(所有指标 p < 0.05)。LASSO 分析确定,结外 MTV 增加和最大病灶 TLG 增加是死亡的强预测因素(AUC 0.74)。pre-LD 总 MTV 较高与 3 级及以上免疫效应细胞相关神经毒性综合征(ICANS)风险升高相关(p = 0.042)。CAR-T 制备期间代谢性肿瘤负荷增加与疾病进展和死亡风险升高相关。由两个变量构成的风险评分可在 CAR-T 输注前对预后进行分层,并可能为风险适配策略提供依据。
PET/CT is used to evaluate relapsed/refractory non-Hodgkin lymphoma (NHL) prior to chimeric antigen receptor T-cell (CAR-T) infusion at two time points: pre-leukapheresis (pre-leuk) and pre-lymphodepletion chemotherapy (pre-LD).
We hypothesized that changes in PET/CT between these time points predict outcomes after CAR-T. Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and other metrics were calculated from pre-leuk and pre-LD PET/CT scans in patients with NHL who received axicabtagene ciloleucel, and assessed for association with outcomes. Sixty-nine patients were analyzed. While single time point PET/CT characteristics were not associated with risk of PD or death, increases from pre-leuk to pre-LD in parenchymal MTV, nodal MTV, TLG of the largest lesion, and total number of lesions were associated with increased risk of death (p < 0.
05 for all). LASSO analysis identified increasing extranodal MTV and increasing TLG of the largest lesion as strong predictors of death (AUC 0. 74). Greater pre-LD total MTV was associated with higher risk of grade 3+ immune effector cell-associated neurotoxicity syndrome (ICANS) (p = 0. 042). Increasing metabolic disease burden during CAR-T manufacturing is associated with increased risk of progression and death. A two variable risk score stratifies prognosis prior to CAR-T infusion and may inform risk-adapted strategies.
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