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
代谢参数预测接受 CAR-T 细胞治疗的复发/难治性大 B 细胞淋巴瘤的生存和毒性
英文原题：Metabolic parameters predict survival and toxicity in chimeric antigen receptor T-cell therapy-treated relapsed/refractory large B-cell lymphoma.
查看英文原题
Metabolic parameters predict survival and toxicity in chimeric antigen receptor T-cell therapy-treated relapsed/refractory large B-cell lymphoma.
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中文摘要
靶向CD19的嵌合抗原受体（CAR）T细胞疗法已改变复发/难治性大B细胞淋巴瘤（LBCL）的治疗，但定量18F-氟脱氧葡萄糖正电子发射断层显像-计算机断层扫描（FDG PET/CT）参数对CAR-T 治疗结局及毒性的预后价值尚缺乏数据。
本研究评估CAR-T 治疗前后代谢参数对生存和毒性的预测价值。研究从单中心接受商业化CD19 CAR-T 治疗的LBCL患者数据库中，回顾性纳入59例CAR-T 输注前后均接受PET/CT检查者。中位随访时间为10.7个月（四分位距2.6–25.5个月）。CAR-T 治疗后总缓解率（完全缓解和部分缓解）为76%（n=45），完全缓解率为53%（n=31）。单变量分析显示，CAR-T 治疗前总病灶糖酵解（TLG）和代谢肿瘤体积（MTV）较低，分别预示治疗后总缓解率提高（OR=4.7，p=0.01；OR=9.5，p=0.03）及完全缓解率提高（OR=12.4，p=0.0004；OR=10.9，p=0.0001）。
治疗前TLG较高与细胞因子释放综合征（CRS）相关（OR=3.25，p=0.04）；治疗前MTV较高与免疫效应细胞相关神经毒性综合征（ICANS）发生相关（OR=4.3，p=0.01）；治疗前SUV较高与3–4级神经系统事件相关（OR=12，p=0.01）。CAR-T 治疗后MTV、TLG和SUVmax较高均与总生存期较差显著相关。多变量分析确定治疗前TLG较高（HR=2.4，p=0.03）、年龄≥60岁（HR=2.7，p=0.03）及单采时存在大体积病灶（≥5 cm；HR=2.5，p=0.02）为无进展生存期较差的独立预后因素。治疗后MTV较高是与总生存期较差相关的最强预后因素。
展开英文摘要原文
CD19-targeted chimeric antigen receptor (CAR) T-cell therapy has revolutionized treatment for patients with relapsed/refractory large B-cell lymphoma (LBCL).
However, data available concerning the impact of the prognostic value of quantitative 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT) parameters on the CAR T-related outcomes and toxicities are limited.
Therefore, we aimed to evaluate the predictive value of pre- and post-CAR T metabolic parameters on survival and toxicities following CAR T-cell therapy. Fifty-nine patients with PET/CT scans done pre-and post-CAR T infusion were retrospectively identified and analyzed in a single institution database of LBCL patients treated with commercial CD19-targeted CAR T-cell therapy. The median follow-up was 10. 7 months [interquartile range (IQR): 2. 6-25. 5 months]. The overall response (complete response-CR and partial response) and CR rates post-CAR T were 76% (n = 45) and 53% (n = 31), respectively. On univariate analysis, low pre-CAR T total lesion glycolysis (TLG) and metabolic tumor volume (MTV) predicted improved overall response post-CAR T (OR = 4. 7, p = 0. 01, OR = 9. 5, p = 0. 03, respectively) and CR post-CAR T (OR = 12.
4, p = 0. 0004, OR = 10. 9, p = 0. 0001, respectively). High TLG pre-CAR T was correlated with cytokine release syndrome (CRS, OR = 3. 25, p = 0. 04). High MTV pre-CAR T was correlated with developing immune effector cell neurotoxicity syndrome (ICANS) events (OR = 4. 3, p = 0. 01), and high SUV pre-CAR T was associated with grade 3-4 neurological events (OR = 12, p = 0. 01).
High MTV/TLG/SUVmax post-CAR T were significantly associated with inferior Overall survival (OS). On multivariate analysis, high TLG pre-CAR T (HR = 2. 4, p = 0. 03), age 60 (HR = 2. 7, p = 0. 03), and bulky disease ( 5 cm) at the time of apheresis (HR = 2. 5, p = 0. 02) were identified to be independent prognostic factors for inferior PFS. High MTV post-CAR T was identified as the most prognostic factor associated with inferior OS.
论文信息
- 作者
- Ababneh HS、Ng AK、Abramson JS、Soumerai JD、Takvorian RW、Frigault MJ、Patel CG
- 单位
- Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.United States
- 期刊
- Hematological oncology2024 Jan
- 原文标识
- PubMed 37795759 · DOI 10.1002/hon.3231