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[18F]FDG PET/CT for prognosis and toxicity prediction of diffuse large B-cell lymphoma patients with chimeric antigen receptor T-cell therapy

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Abstract

Purpose

Chimeric antigen receptor (CAR) T-cell therapy has been confirmed to benefit patients with relapsed and/or refractory diffuse large B-cell lymphoma (DLBCL). It is important to provide precise and timely predictions of the efficacy and toxicity of CAR T-cell therapy. In this study, we evaluated the value of [18F]fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) combining with clinical indices and laboratory indicators in predicting outcomes and toxicity of anti-CD19 CAR T-cell therapy for DLBCL patients.

Methods

Thirty-eight DLBCL patients who received CAR T-cell therapy and underwent [18F]FDG PET/CT within 3 months before (pre-infusion) and 1 month after CAR T-cell infusion (M1) were retrospectively reviewed and regularly followed up. Maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), metabolic tumor volume (MTV), clinical indices, and laboratory indicators were recorded at pre-infusion and M1 time points, and changes in these indices were calculated. Progression-free survival (PFS) and overall survival (OS) were as endpoints. Based on the multivariate Cox regression analysis, two predictive models for PFS and OS were developed and evaluated the efficiency. Pre-infusion indices were subjected to predict the grade of cytokine release syndrome (CRS) resulting from toxic reactions.

Results

For survival analysis at a median follow-up time of 18.2 months, patients with values of international prognostic index (IPI), SUVmax at M1, and TLG at M1 above their optimal thresholds had a shorter PFS (median PFS: 8.1 months [IPI ≥ 2] vs. 26.2 months [IPI < 2], P = 0.025; 3.1 months [SUVmax ≥ 5.69] vs. 26.8 months [SUVmax < 5.69], P < 0.001; and 3.1 months [TLG ≥ 23.79] vs. 26.8 months [TLG < 23.79], P < 0.001). In addition, patients with values of SUVmax at M1 and ∆SUVmax% above their optimal thresholds had a shorter OS (median OS: 12.6 months [SUVmax ≥ 15.93] vs. ‘not reached’ [SUVmax < 15.93], P < 0.001; 32.5 months [∆SUVmax% ≥ −46.76] vs. ‘not reached’ [∆SUVmax% < −46.76], P = 0.012). Two novel predictive models for PFS and OS were visualized using nomogram. The calibration analysis and the decision curves demonstrated good performance of the models. Spearman’s rank correlation (rs) analysis revealed that the CRS grade correlated strongly with the pre-infusion SUVmax (rs = 0.806, P < 0.001) and moderately with the pre-infusion TLG (rs = 0.534, P < 0.001). Multinomial logistic regression analysis revealed that the pre-infusion value of SUVmax correlated with the risk of developing a higher grade of CRS (P < 0.001).

Conclusion

In this group of DLBCL patients who underwent CAR T-cell therapy, SUVmax at M1, TLG at M1, and IPI were independent risk factors for PFS, and SUVmax at M1 and ∆SUVmax% for OS. Based on these indicators, two novel predictive models were established and verified the efficiency for evaluating PFS and OS. Moreover, pre-infusion SUVmax correlated with the severity of any subsequent CRS. We conclude that metabolic parameters measured using [18F]FDG PET/CT can identify DLBCL patients who will benefit most from CAR T-cell therapy, and the value before CAR T-cell infusion may predict its toxicity in advance.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors thank LiWen Bianji for editing the manuscript.

Funding

This work was supported by National Natural Science Foundation of China (grants 82030052), Hubei Province Science and Technology Innovation Team ([2022] No. 72) and Key Project of Hubei Province Natural Science Foundation (No. 2021CFA008).

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Authors and Affiliations

  1. Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China

    Jinbo Gui, Mengting Li, Xiao Zhang & Xiaoli Lan

  2. Hubei Key Laboratory of Molecular Imaging, Wuhan, 430022, China

    Jinbo Gui, Mengting Li, Xiao Zhang & Xiaoli Lan

  3. Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Wuhan, Hubei, 430022, China

    Jinbo Gui, Mengting Li, Xiao Zhang, Heng Mei & Xiaoli Lan

  4. Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China

    Jia Xu & Heng Mei

  5. Hubei Clinical Medical Center of Cell Therapy for Neoplastic Disease, Wuhan, 430022, China

    Jia Xu & Heng Mei

Authors
  1. Jinbo Gui
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  2. Mengting Li
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  4. Xiao Zhang
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Contributions

Dr. Lan X and Mei H contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Gui J, Li M, Xu J, and Zhang X. The first draft of the manuscript was written by Gui J and Li M. Lan X, and Mei H revised the work critically for important intellectual content. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Heng Mei or Xiaoli Lan.

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This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. All included data were collected as part of a retrospective study protocol approved by the local institutional ethics committee, which waived written informed consent.

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Gui, J., Li, M., Xu, J. et al. [18F]FDG PET/CT for prognosis and toxicity prediction of diffuse large B-cell lymphoma patients with chimeric antigen receptor T-cell therapy. Eur J Nucl Med Mol Imaging (2024). https://doi.org/10.1007/s00259-024-06667-0

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