Predictive value of maximum tumor dissemination (Dmax) in lymphoma patients treated with CD19-specific CAR T-Cells

CD19-specific chimeric antigen receptor T-cell therapy (CART) has emerged as effective treatment for relapsed or refractory (r/r) lymphoma. The maximum distance (Dmax) of lymphoma lesions holds potential as prognostic imaging biomarker in lymphoma treated with conventional therapies, but evidence in the context of CART remains scarce and further studies are needed to clarify its clinical relevance. We evaluated Dmax at baseline imaging as a potential prognostic tool for assessment of metabolic and overall response, progression-free survival (PFS) and overall survival (OS).

Consecutive r/r lymphoma patients with (PET/)CT imaging at baseline (BL) before lymphodepletion and subsequent CAR T-cell transfusion were included. Dmax was measured in cm at BL. Patients were divided by tertiles into three equal sized groups according to Dmax. Ann Arbor stages were calculated at baseline and the sum of product diameters (SPD) was used to represent tumor burden (TB). Overall response according to Lugano criteria and the Deauville score were determined at day 90 PET/CT imaging.

Thirty-nine patients met the inclusion criteria. Median Dmax was 40.0 cm (IQR: 16.4-70.3 cm) at BL. Median TB decreased from BL with 4,095 mm² to 770 mm² at FU imaging. Median TB at BL was significantly higher in the Dmax intermediate and high group compared to the Dmax low group (p = 0.005) with 7,222 mm² (IQR: 3,355-11,941 mm²), 4,649 mm² (IQR: 2,376-10,406 mm²) and 1,739 mm² (IQR: 715-7,402 mm²), respectively. Dmax intermediate and high group showed significantly higher Ann Arbor stages (p < 0.001). The survival analysis revealed a significantly (p = 0.030) shorter PFS in the Dmax high group compared to the other patients (91 vs. 364 days), but no relevant differences in OS (p = 0.151).

Patients with high Dmax showed a shorter PFS, but no significant differences in OS. Dmax is a useful parameter for characterizing tumor dissemination, which could also be incorporated into scores due to its interval scale.