Conventional and novel [18F]FDG PET/CT features as predictors of CAR-T cell therapy outcome in large B-cell lymphoma

Doris Leithner, Jessica R. Flynn, Sean M. Devlin, Audrey Mauguen, Teng Fei, Shang Zeng, Junting Zheng, Brandon S. Imber, Harper Hubbeling, Marius E. Mayerhoefer, Akshay Bedmutha, Efrat Luttwak, Magdalena Corona, Parastoo B. Dahi, Alejandro Luna de Abia, Ivan Landego, Richard J. Lin, M. Lia Palomba, Michael Scordo, Jae H. ParkAna Alarcon Tomas, Gilles Salles, Daniel Lafontaine, Laure Michaud, Gunjan L. Shah, Miguel Angel Perales, Roni Shouval, Heiko Schöder

Research output: Contribution to journalLetterpeer-review

1 Scopus citations

Abstract

Relapse and toxicity limit the effectiveness of chimeric antigen receptor T-cell (CAR-T) therapy for large B-cell lymphoma (LBCL), yet biomarkers that predict outcomes and toxicity are lacking. We examined radiomic features extracted from pre-CAR-T 18F-fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) scans (n = 341) of 180 patients (121 male; median age, 66 years). Three conventional (maximum standardized uptake value [SUVmax], metabolic tumor volume [MTV], total lesion glycolysis [TLG]) and 116 novel radiomic features were assessed, along with inflammatory markers, toxicities, and outcomes. At both pre-apheresis and pre-infusion time points, conventional PET features of disease correlated with elevated inflammatory markers. At pre-infusion, MTV was associated with grade ≥ 2 cytokine release syndrome (odds ratio [OR] for 100 mL increase: 1.08 [95% confidence interval (CI), 1.01–1.20], P = 0.031), and SUVmax was associated with failure to achieve complete response (CR) (OR 1.72 [95% CI, 1.24–2.43], P < 0.001). Higher pre-apheresis and pre-infusion MTV values were associated with shorter progression-free survival (PFS) (HR for 10-unit increase: 1.11 [95% CI, 1.05–1.17], P < 0.001; 1.04 [95% CI, 1.02–1.07], P < 0.001) and shorter overall survival (HR for 100-unit increase: 1.14 [95% CI, 1.07–1.21], P < 0.001; 1.04 [95% CI, 1.02–1.06], P < 0.001). A combined MTV and LDH measure stratified patients into high and low PFS risk groups. Multiple pre-infusion novel radiomic features were associated with CR. These quantitative conventional [18F]FDG PET/CT features obtained before CAR-T cell infusion, which were correlated with inflammation markers, may provide prognostic biomarkers for CAR-T therapy efficacy and toxicity. The use of conventional and novel radiomic features may thus help identify high-risk patients for earlier interventions.

Original languageEnglish
Article number21
JournalJournal of Hematology and Oncology
Volume17
Issue number1
DOIs
StatePublished - 23 Apr 2024
Externally publishedYes

Bibliographical note

Publisher Copyright:
© The Author(s) 2024.

Keywords

  • Biomarker
  • CAR-T
  • Immunotherapy
  • Lymphoma
  • Positron emission tomography
  • Radiomics

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