在Axicabtagene Ciloleucel CAR-T细胞治疗之前，对侵袭性非霍奇金淋巴瘤进行代谢PET/CT分析：进展性疾病、生存和毒性的预测因子。
Metabolic PET/CT analysis of aggressive Non-Hodgkin lymphoma prior to Axicabtagene Ciloleucel CAR-T infusion: predictors of progressive disease, survival, and toxicity.
发表日期：2023 Aug 18
作者：
William G Breen, Jason R Young, Matthew A Hathcock, Roman O Kowalchuk, Matthew P Thorpe, Radhika Bansal, Arushi Khurana, N Nora Bennani, Jonas Paludo, Jose Villasboas Bisneto, Yucai Wang, Stephen M Ansell, Jennifer L Peterson, Patrick B Johnston, Scott C Lester, Yi Lin
来源：
Blood Cancer Journal
摘要：
在chimeric antigen receptor T-cell（CAR-T）输注之前，使用PET/CT评估复发/难治性非霍奇金淋巴瘤（non-Hodgkin lymphoma，NHL）的两个时间点：白细胞浓缩前（pre-leuk）和淋巴缺血化疗前（pre-LD）。我们假设在这两个时间点之间PET/CT的变化可以预测CAR-T后的结果。从接受axicabtagene ciloleucel治疗的NHL患者的pre-leuk和pre-LD PET/CT扫描中计算出代谢性肿瘤体积（metabolic tumor volume，MTV）、总病变糖代谢（total lesion glycolysis，TLG）和其他指标，并评估其与结果的关联性。分析了69名患者。单一时间点的PET/CT特征与PD或死亡风险无关，但是从pre-leuk到pre-LD的肺实质MTV、淋巴结MTV、最大病变的TLG和病变总数的增加与死亡风险增加相关（所有p < 0.05）。LASSO分析确定了外淋巴结MTV和最大病变的TLG的增加是死亡的强预测因子（AUC 0.74）。pre-LD的总MTV较大与3+级免疫效应细胞相关的神经毒性综合征（ICANS）的风险增加相关（p = 0.042）。在CAR-T制造过程中代谢性疾病负担的增加与进展和死亡的风险增加相关。一种两个变量的风险评分可以在CAR-T输注前对预后进行分层，并可为风险适应性策略提供信息。© 2023 Springer Nature Limited.
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.© 2023. Springer Nature Limited.