Department of Radiology, University Hospital, LMU Munich, Munich, Germany.
Laboratory for Translational Cancer Immunology, Gene Center of the LMU Munich, Munich, Germany; German Cancer Consortium (DKTK) and Bavarian Center for Cancer Research (BZKF), partner site Munich, Munich, Germany; Department of Medicine III, University Hospital, LMU Munich, Munich, Germany.
Cytotherapy. 2023 Sep;25(9):986-992. doi: 10.1016/j.jcyt.2023.03.007. Epub 2023 Apr 11.
Chimeric antigen receptor T-cell therapy (CART) prolongs survival for patients with refractory or relapsed lymphoma, yet its efficacy is affected by the tumor burden. The relevance of tumor kinetics before infusion is unknown. We aimed to study the prognostic value of the pre-infusion tumor growth rate (TGR) for progression-free (PFS) and overall survival (OS).
Consecutive patients with available pre-baseline (pre-BL) and baseline (BL) computed tomography or positron emission tomography/computed tomography scan before CART were included. TGR was determined as change of Lugano criteria-based tumor burden between pre-BL, BL and follow-up examinations (FU) in relation to days between imaging exams. Overall response rate (ORR), depth or response (DoR) and PFS were determined based on Lugano criteria. Multivariate regression analysis studied association of TGR with ORR and DoR. Proportional Cox regression analysis studied association of TGR with PFS and OS.
In total, 62 patients met the inclusion criteria. The median TGR was 7.5 mm/d (interquartile range -14.6 mm/d to 48.7 mm/d); TGR was positive (TGR) in 58% of patients and negative (TGR, indicating tumor shrinkage) in 42% of patients. Patients who were TGR had a 90-day (FU2) ORR of 62%, a DoR of -86% and a median PFS of 124 days. Patients who were TGR had a 90-day ORR of 44%, DoR of -47% and a median PFS of 105 days. ORR and DoR were not associated with slower TGR (P = 0.751, P = 0.198). Patients with an increase of TGR from pre-BL over BL to 30-day FU (FU1) ≥100% (TGR) showed a significant association with shorter median PFS (31 days versus 343 days, P = 0.002) and shorter median OS after CART (93 days versus not reached, P < 0.001), compared with patients with TGR.
In the context of CART, differences in pre-infusion tumor kinetics showed minor differences in ORR, DoR, PFS and OS, whereas the change of the TGR from pre-BL to 30-day FU significantly stratified PFS and OS. In this patient population of refractory or relapsed lymphomas, TGR is readily available based on pre-BL imaging, and its change throughout CART should be explored as a potential novel imaging biomarker of early response.
嵌合抗原受体 T 细胞疗法（CART）可延长难治性或复发性淋巴瘤患者的生存期，但疗效受肿瘤负担的影响。输注前肿瘤动力学的相关性尚不清楚。我们旨在研究输注前肿瘤生长率（TGR）对无进展生存期（PFS）和总生存期（OS）的预后价值。
纳入了接受 CART 治疗前有可用基线前（pre-BL）和基线（BL）计算机断层扫描或正电子发射断层扫描/计算机断层扫描检查的连续患者。TGR 是根据 Lugano 标准，通过 BL 和随访（FU）检查之间的成像检查天数来确定肿瘤负荷的变化。根据 Lugano 标准确定总缓解率（ORR）、深度或反应（DoR）和 PFS。多变量回归分析研究了 TGR 与 ORR 和 DoR 的相关性。比例 Cox 回归分析研究了 TGR 与 PFS 和 OS 的相关性。
共有 62 名患者符合纳入标准。中位 TGR 为 7.5mm/d（四分位距-14.6mm/d 至 48.7mm/d）；58%的患者 TGR 为阳性（TGR），42%的患者 TGR 为阴性（TGR，表示肿瘤缩小）。TGR 患者的 90 天（FU2）ORR 为 62%，DoR 为-86%，中位 PFS 为 124 天。TGR 患者的 90 天 ORR 为 44%，DoR 为-47%，中位 PFS 为 105 天。ORR 和 DoR 与较慢的 TGR 无关（P=0.751，P=0.198）。从 BL 到 30 天 FU（FU1）TGR 增加≥100%（TGR）的患者与较短的中位 PFS（31 天与 343 天，P=0.002）和 CART 后较短的中位 OS（93 天与未达到，P<0.001）显著相关，与 TGR 患者相比。
在 CART 背景下，输注前肿瘤动力学的差异在 ORR、DoR、PFS 和 OS 方面差异较小，而 TGR 从 BL 到 30 天 FU 的变化显著分层了 PFS 和 OS。在这个难治性或复发性淋巴瘤的患者群体中，TGR 可基于 BL 成像获得，在整个 CART 过程中其变化可作为早期反应的潜在新的影像学生物标志物进行探索。
