通过输注前肿瘤动力学对 Lugano 标准进行修改，可改善接受 CAR-T 细胞治疗的淋巴瘤患者的早期生存预测

Chimeric antigen receptor T-cell therapy (CART) is effective for patients with refractory or relapsed lymphoma with prolongation of survival. We aimed to improve the prediction of Lugano criteria for overall survival (OS) at 30-day follow-up (FU1) by including the pre-infusion tumor growth rate (TGR pre-BL ) and its early change to 30-day FU1 imaging (TGR post-BL ).

Consecutive patients with pre-baseline (pre-BL), baseline (BL) and FU1 imaging with CT or positron emission tomography/CT before CART were included. TGR was defined as change of Lugano criteria-based tumor burden between pre-BL, BL and FU1 examinations in relation to days between imaging examinations. Overall response and progression-free survival were determined based on Lugano criteria. Proportional Cox regression analysis studied association of TGR with OS. For survival analysis, OS was analyzed using Kaplan-Meier survival curves.

Fifty-nine out of 81 patients met the inclusion criteria. At 30-day FU1 8 patients (13.6%) had a complete response (CR), 25 patients (42.4%) a partial response (PR), 15 patients (25.4%) a stable disease (SD), and 11 patients (18.6%) a progressive disease (PD) according to CT-based Lugano criteria. The median TGR pre-BL was -0.6 mm 2 /day, 24.4 mm 2 /day, -5.1 mm 2 /day, and 18.6 mm 2 /day and the median TGR post-BL was -16.7 mm 2 /day, -102.0 mm 2 /day, -19.8 mm 2 /day and 8.5 mm 2 /day in CR, PR, SD, and PD patients, respectively. PD patients could be subclassified into a cohort with an increase in TGR (7 of 11 patients (64%), PD TGR pre-to-post-BL INCR ) and a cohort with a decrease in TGR (4 of 11 patients (36%), PD TGR pre-to-post-BL DECR ) from pre-BL to post-BL. PD TGR pre-to-post-BL DECR patients exhibited similar OS to patients classified as SD, while PD TGR pre-to-post-BL INCR patients had significantly shorter OS (65 days vs 471 days, p<0.001).

In the context of CART, the additional use of TGR pre-BL and its change to TGR post-BL determined at 30-day FU1 showed better OS prognostication for patients with overall PD according to Lugano criteria. Therefore, this modification of the Lugano classification should be explored as a potential novel imaging biomarker of early response and should be validated prospectively in future studies.