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

Winkelmann, Michael; Achhammer, Philipp; Blumenberg, Viktoria; Rejeski, Kai; Bücklein, Veit L.; Schmidt, Christian; Sheikh, Gabriel T.; Brendel, Matthias; Ricke, Jens; Bergwelt-Baildon, Michael von; Subklewe, Marion; Kunz, Wolfgang G. (2025): Predictive value of maximum tumor dissemination (Dmax) in lymphoma patients treated with CD19-specific CAR T-Cells. Cancer Imaging, 25: 135. ISSN 1470-7330

Abstract

Objectives

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).

Material & methods

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.

Results

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 mm 2 to 770 mm 2 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 mm 2 (IQR: 3,355–11,941 mm 2 ), 4,649 mm 2 (IQR: 2,376–10,406 mm 2 ) and 1,739 mm 2 (IQR: 715–7,402 mm 2 ), 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).

Conclusions

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.

• Doc-Type: Article (LMU Hospital)
• Organisational unit (Faculties): 07 Medicine > Munich Cluster for Systems Neurology (SyNergy); 07 Medicine > Medical Center of the University of Munich > Medical Clinic and Outpatient Clinic III (Oncology); 07 Medicine > Medical Center of the University of Munich > Clinic and Polyclinic for Nuclear Medicine; 07 Medicine > Medical Center of the University of Munich > Clinic and Polyclinic for Radiology
• DFG subject classification of scientific disciplines: Life sciences
• DFG: Funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - 390857198
• DFG: Funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - 491502892