Abstract:

Background and purpose: Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) can be treated with chimeric antigen receptor T-cell (CAR-T) therapy. Imaging-based biomarkers may help identify patients likely to achieve clinical response to this immunotherapy. In this study, an 18-f1uoro-2-deoxy-D-glucose positron emission tomography-computed tomography (¹⁸F-FDG PET/CT) based model was developed to assess the progression-free survival (PFS) and overall survival (OS) of patients with relapsed or refractory (R/R) DLBCL who received CAR-T therapy. Methods: We retrospectively analyzed clinical and imaging data from patients with DLBCL who underwent CAR-T therapy at the First Affiliated Hospital of Soochow University between March 2017 and January 2022. Inclusion criteria: ① age ≥18 years old; ② pathologically confirmed R/R DLBCL; ③ ¹⁸F-FDG PET/CT performed before CAR-T cell therapy; ④ complete clinicopathologic data; ⑤ patients must have measurable lesions. Exclusion criteria: ① patients with incomplete clinical or imaging data; ② patients with other types of malignant tumors; ③ patients who have received granulocyte colony-stimulating factor treatment within 1 month prior to PET/CT scan. This study was reviewed by the Ethics Committee of the First Affiliated Hospital of Soochow University (ID: 2025256). Receiver operating characteristic (ROC) curves were used to determine the optimal thresholds for maximum standardized uptake value (SUV_max), tumor metabolic volume (MTV), and total glycolysis (TLG), and the patients were classified into high-risk and low-risk groups. Univariate and multivariate Cox regression analyses were used to identify potential prognostic factors and construct predictive models, which were visualized by drawing nomogram. Area under the ROC curve was used to assess the performance of each model. Results: A total of 61 patients (37 male patients and 24 female patients, aged 26-75 years) with DLBCL who underwent ¹⁸F-FDG PET/CT prior to CAR-T infusion were included. The median follow-up was 14 months; 36 patients (59.02%) had disease progression and 25 patients (40.98%) died. Multivariate analysis showed that grade of cytokine release syndrome (CRS) [Hazard ratio (HR)=3.671; P=0.003] and MTV (HR=0.171, P=0.004) were independent prognostic factors for OS; Eastern Cooperative Oncology Group (ECOG) score (HR=2.411, P=0.019), grade of CRS (HR=2.499; P=0.027), and MTV (HR=0.338, P=0.007) were independent prognostic factors for PFS. The combined model (MTV, ECOG score, grade of CRS) was better than the clinical model (ECOG score, grade of CRS), and metabolic parameter model (MTV) in predicting PFS and OS. Conclusion: ¹⁸F-FDG PET/CT metabolic parameter MTV in combination with traditional clinical risk factors (ECOG score, Grade of CRS) could identify patients with ultra-high risk of DLBCL.

Key words: Diffuse large B-cell lymphoma, PET/CT, MTV, CAR-T, Prognosis