*Article* **Value of CT-Textural Features and Volume-Based PET Parameters in Comparison to Serologic Markers for Response Prediction in Patients with Diffuse Large B-Cell Lymphoma Undergoing CD19-CAR-T Cell Therapy**

**Christian Philipp Reinert 1,\*, Regine Mariette Perl 1, Christoph Faul 2, Claudia Lengerke 2, Konstantin Nikolaou 1,3, Helmut Dittmann 4, Wolfgang A. Bethge 2,† and Marius Horger 1,†**


**Abstract:** The goal of this study was to investigate the value of CT-textural features and volumebased PET parameters in comparison to serologic markers for response prediction in patients with diffuse large B-cell lymphoma (DLBCL) undergoing cluster of differentiation (CD19)-chimeric antigen receptor (CAR)-T cell therapy. We retrospectively analyzed the whole-body (WB)-metabolic tumor volume (MTV), the WB-total lesion glycolysis (TLG) and first order textural features derived from 18F-FDG-PET/CT, as well as serologic parameters (C-reactive protein [CRP] and lactate dehydrogenase [LDH], leucocytes) prior and after CAR-T cell therapy in 21 patients with DLBCL (57.7 ± 14.7 year; 7 female). Interleukin 6 (IL-6) and IL-2 receptor peaks were monitored after treatment onset and compared with patient outcome judged by follow-up 18F-FDG-PET/CT. In 12/21 patients (57%), complete remission (CR) was observed, whereas 9/21 patients (43%) showed partial remission (PR). At baseline, WB-MTV and WB-TLG were lower in patients achieving CR (35 ± 38 mL and 319 ± 362) compared to patients achieving PR (88 ± 110 mL and 1487 ± 2254; *p* < 0.05). The "entropy" proved lower (1.81 ± 0.09) and "uniformity" higher (0.33 ± 0.02) in patients with CR compared to PR (2.08 ± 0.22 and 0.28 ± 0.47; *p* < 0.05). Patients achieving CR had lower levels of CRP, LDH and leucocytes at baseline compared to patients achieving PR (*p* < 0.05). In the entire cohort, WB-MTV and WB-TLG decreased after therapy onset (*p* < 0.01) becoming not measurable in the CR-group. Leucocytes and CRP significantly dropped after therapy (*p* < 0.01). The IL-6 and IL-2R peaks after therapy were lower in patients with CR compared to PR (*p* > 0.05). In conclusion, volume-based PET parameters derived from PET/CT and CT-textural features have the potential to predict therapy response in patients with DLBCL undergoing CAR-T cell therapy.

**Keywords:** diffuse-large B cell lymphoma; chimeric antigen receptor T cells; response assessment; positron emission tomography; computed tomography; texture analysis
