代谢参数可预测嵌合抗原受体 T 细胞疗法治疗复发/难治性大 B 细胞淋巴瘤的生存和毒性。
Metabolic parameters predict survival and toxicity in chimeric antigen receptor T-cell therapy-treated relapsed/refractory large B-cell lymphoma.
机构信息
Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Department of Radiation Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
出版信息
Hematol Oncol. 2024 Jan;42(1):e3231. doi: 10.1002/hon.3231. Epub 2023 Oct 5.
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.
CD19 靶向嵌合抗原受体 (CAR) T 细胞疗法彻底改变了复发/难治性大 B 细胞淋巴瘤 (LBCL) 患者的治疗方法。然而,关于定量 18F-氟脱氧葡萄糖正电子发射断层扫描-计算机断层扫描 (FDG PET/CT) 参数的预后价值对 CAR T 相关结局和毒性的影响的数据有限。因此,我们旨在评估 CAR T 细胞治疗前和后代谢参数对 CAR T 相关生存和毒性的预测价值。我们在单中心 LBCL 患者接受商业 CD19 靶向 CAR T 细胞治疗的数据库中回顾性地确定并分析了 59 例接受 CAR T 输注前后进行 PET/CT 扫描的患者。中位随访时间为 10.7 个月[四分位距 (IQR):2.6-25.5 个月]。CAR T 后总体反应 (完全缓解-CR 和部分缓解) 和 CR 率分别为 76%(n=45)和 53%(n=31)。在单因素分析中,CAR T 前低总病变糖酵解 (TLG) 和代谢肿瘤体积 (MTV) 预测 CAR T 后总体反应改善(OR=4.7,p=0.01,OR=9.5,p=0.03)和 CAR T 后 CR(OR=12.4,p=0.0004,OR=10.9,p=0.0001)。CAR T 前高 TLG 与细胞因子释放综合征 (CRS,OR=3.25,p=0.04) 相关。CAR T 前高 MTV 与发生免疫效应细胞神经毒性综合征 (ICANS) 事件相关(OR=4.3,p=0.01),CAR T 前高 SUV 与 3-4 级神经事件相关(OR=12,p=0.01)。CAR T 后高 MTV/TLG/SUVmax 与较差的总生存 (OS) 显著相关。多因素分析显示,CAR T 前高 TLG(HR=2.4,p=0.03)、年龄≥60 岁(HR=2.7,p=0.03)和采集时大肿块(≥5cm)(HR=2.5,p=0.02)被确定为无进展生存期差的独立预后因素。CAR T 后高 MTV 被确定为与较差 OS 相关的最具预后的因素。