Ababneh Hazim S, Frigault Matthew J, Ng Andrea K, Patel Chirayu G
Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Division of Hematology & Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Hematol Oncol. 2025 Jan;43(1):e70025. doi: 10.1002/hon.70025.
18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) parameters have shown a significant prognostic role in relapsed/refractory large B-cell lymphoma (LBCL) patients undergoing CD19-targeted chimeric antigen receptor (CAR) T-cell therapy. While a substantial body of evidence exists on the prognostic value of PET/CT parameters in peri-CAR T setting, data available on the prognostic value of PET/CT parameters following CAR T-cell therapy failure is lacking. Therefore, we sought to analyze the PET/CT scans of LBCL patients who experienced post-CAR T relapsed/progressive disease and subsequently received salvage therapies. Thirty-three LBCL patients who had PET-CT scans done demonstrating post-CAR T failure and then received salvage therapies [as a first salvage modality: RT alone, nine patients; combined modality therapy (CMT), seven patients; systemic therapy (ST) alone, 17 patients] were analyzed. The median follow-up after CAR T-cell infusion was 11.7 months [interquartile range (IQR): 5.1-24.4 months], and the median follow-up after post-CAR T salvage therapy was 7.3 months (IQR: 2.7-19.1 months). The median timeframe for the PET scan showing post-CAR T failure was 2.4 months (IQR: 0.96-5.0 months). On univariable analysis from salvage therapy start date, high metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were associated with inferior overall survival (OS) (Hazard ratio -HR = 8.4, p < 0.0001; HR = 3.2, p = 0.01, respectively). High MTV was associated with a non-significant trend of inferior progression-free survival (PFS) (HR = 3.5, p = 0.09). High maximum standardized uptake value (SUVmax) was not associated with inferior OS or inferior PFS. On multivariable analysis from salvage therapy start date, high MTV (HR = 4.6, 95% CI: 1.5-14.3, p = 0.009) was identified to be an independent prognostic factor for inferior OS. High International Prognostic Index (IPI) (≥ 3) at the time of salvage therapy (HR = 2.5, 95% CI: 1.1-5.6, p = 0.02) was significantly associated with inferior PFS. Our study shows that semiquantitative PET/CT metrics, especially MTV, are significant prognostic indicators of overall survival in this highly refractory population after CAR T-cell therapy failure, potentially refining prognostic and treatment approaches beyond conventional parameters like IPI.
18F-氟脱氧葡萄糖正电子发射断层扫描-计算机断层扫描（18F-FDG PET/CT）参数已显示出在接受靶向CD19嵌合抗原受体（CAR）T细胞治疗的复发/难治性大B细胞淋巴瘤（LBCL）患者中的显著预后作用。虽然有大量证据表明PET/CT参数在CAR T治疗期间的预后价值，但缺乏关于CAR T细胞治疗失败后PET/CT参数预后价值的可用数据。因此，我们试图分析经历CAR T治疗后复发/疾病进展并随后接受挽救治疗的LBCL患者的PET/CT扫描结果。分析了33例LBCL患者，他们进行了PET-CT扫描，显示CAR T治疗失败，随后接受了挽救治疗[作为第一种挽救方式：单纯放疗，9例患者；综合治疗（CMT），7例患者；单纯全身治疗（ST），17例患者]。CAR T细胞输注后的中位随访时间为11.7个月[四分位间距（IQR）：5.1-24.4个月]，CAR T治疗后挽救治疗后的中位随访时间为7.3个月（IQR：2.7-19.1个月）。显示CAR T治疗失败的PET扫描的中位时间为2.4个月（IQR：0.96-5.0个月）。从挽救治疗开始日期进行单变量分析，高代谢肿瘤体积（MTV）和总病变糖酵解（TLG）与较差的总生存期（OS）相关（风险比-HR = 8.4，p < 0.0001；HR = 3.2，p = 0.01）。高MTV与无进展生存期（PFS）较差的非显著趋势相关（HR = 3.5，p = 0.09）。高最大标准化摄取值（SUVmax）与较差的OS或较差的PFS无关。从挽救治疗开始日期进行多变量分析，高MTV（HR = 4.6，95%置信区间：1.5-14.3，p = 0.009）被确定为较差OS的独立预后因素。挽救治疗时高国际预后指数（IPI）（≥3）（HR = 2.5，95%置信区间：1.1-5.6，p = 0.02）与较差的PFS显著相关。我们的研究表明，半定量PET/CT指标，尤其是MTV，是CAR T细胞治疗失败后这一高度难治性人群总生存期的重要预后指标，可能会完善超越IPI等传统参数的预后和治疗方法。
