Prognostic Value of Radiomic Features of 18F-FDG PET/CT in Patients With B-Cell Lymphoma Treated With CD19/CD22 Dual-Targeted Chimeric Antigen Receptor T Cells.

Yeye Zhou,Bin Zhang,Jihui Li,Shengming Deng,Shibiao Sang,Xiaoyi Zhang,Tongtong Jia,Na Dai

doi:10.3389/fonc.2022.834288

Abstract

ObjectiveIn the present study, we aimed to evaluate the prognostic value of PET/CT-derived radiomic features for patients with B-cell lymphoma (BCL), who were treated with CD19/CD22 dual-targeted chimeric antigen receptor (CAR) T cells. Moreover, we explored the relationship between baseline radiomic features and the occurrence probability of cytokine release syndrome (CRS).MethodsA total of 24 BCL patients who received 18F-FDG PET/CT before CAR T-cell infusion were enrolled in the present study. Radiomic features from PET and CT images were extracted using LIFEx software, and the least absolute shrinkage and selection operator (LASSO) regression was used to select the most useful predictive features of progression-free survival (PFS) and overall survival (OS). Receiver operating characteristic curves, Cox proportional hazards model, and Kaplan-Meier curves were conducted to assess the potential prognostic value.ResultsContrast extracted from neighbourhood grey-level different matrix (NGLDM) was an independent predictor of PFS (HR = 15.16, p = 0.023). MYC and BCL2 double-expressor (DE) was of prognostic significance for PFS (HR = 7.02, p = 0.047) and OS (HR = 10.37, p = 0.041). The combination of NGLDM_ContrastPET and DE yielded three risk groups with zero (n = 7), one (n = 11), or two (n = 6) factors (p < 0.0001 and p = 0.0004, for PFS and OS), respectively. The PFS was 85.7%, 63.6%, and 0%, respectively, and the OS was 100%, 90.9%, and 16.7%, respectively. Moreover, there was no significant association between PET/CT variables and CRS.ConclusionsIn conclusion, radiomic features extracted from baseline 18F-FDG PET/CT images in combination with genomic factors could predict the survival outcomes of BCL patients receiving CAR T-cell therapy.

Highlights

Diffuse large B-cell lymphoma (DLBCL) is the most common type of malignant lymphomas in adults, accounting for 30-40% of all non-Hodgkin lymphoma (NHL) worldwide, and DLBCL exhibits a higher prevalence in developing countries [1, 2]
We aimed to investigate the capacity of radiomic features extracted from baseline18F-FDG PET/CT to predict the survival of BCL patients treated with CD19/CD22 dual-targeted Chimeric antigen receptor (CAR) T-cell therapies
Six patients died after infusion, with a median time of 2.5 months, and all deaths were attributed to the progression of lymphoma (Figures 3A, B)

Summary

Introduction

Diffuse large B-cell lymphoma (DLBCL) is the most common type of malignant lymphomas in adults, accounting for 30-40% of all non-Hodgkin lymphoma (NHL) worldwide, and DLBCL exhibits a higher prevalence in developing countries [1, 2]. Chimeric antigen receptor (CAR) T-cell therapies targeting CD19 are a promising approach for the treatment of relapsed/refractory (R/R) B-cell malignancies. The complete remission (CR) rate in patients with R/R B-cell acute lymphoblastic leukemia (B-ALL), who received CD19 CAR T-cell therapies, is approximately 90%, while it is only 50% in patients with R/R B-cell NHL (B-NHL) [4,5,6]. 30% of relapses after CD19 CAR T-cell therapy are characterized by CD19 antigen loss through a variety of mechanisms, including antigen escape or lineage switch [7, 8]. Evidence from some studies of solid tumors has shown that compared with single-antigen targeting, dual- or multi-antigen targeting CAR T-cells may result in synergistic effects, which can optimize response rates and prevent antigen escape [9, 10]. Like CD19, CD22 is expressed in most B-cell malignancies, which is an effective target for CAR T-cell therapy in B-cell hematological malignancies [11]

Methods

Results

Conclusion