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Hypoxia-specific imaging in patients with lymphoma undergoing CAR-T therapy

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Intratumoral hypoxia in non-Hodgkin’s Lymphoma (NHL) may interfere with chimeric antigen receptor T-cell (CAR-T) function. We conducted a single-center pilot study (clinicaltrials.gov ID NCT04409314) of [18F]fluoroazomycin arabinoside, a hypoxia-specific radiotracer abbreviated as [18F]FAZA, to assess the feasibility of this positron emission tomography (PET) imaging modality in this population.

Methods

Patients with relapsed NHL being evaluated for CAR-T therapy received a one-time [18F]FAZA PET scan before pre-CAR-T lymphodepletion. A tumor to mediastinum (T/M) ratio of 1.2 or higher with regard to [18F]FAZA uptake was defined as positive for intratumoral hypoxia. We planned to enroll 30 patients with an interim futility analysis after 16 scans.

Results

Of 16 scanned patients, 3 had no evidence of disease by standard [18F]fluorodeoxyglucose PET imaging before CAR-T therapy. Six patients (38%) had any [18F]FAZA uptake above background. Using a T/M cutoff of 1.20, only one patient (a 68-year-old male with relapsed diffuse large B-cell lymphoma) demonstrated intratumoral hypoxia in an extranodal chest wall lesion (T/M 1.35). Interestingly, of all 16 scanned patients, he was the only patient with progressive disease within 1 month of CAR-T therapy. However, because of our low overall proportion of positive scans, our study was stopped for futility.

Conclusions

Our pilot study identified low-level [18F]FAZA uptake in a small number of patients with NHL receiving CAR-T therapy. The only patient who met our pre-specified threshold for intratumoral hypoxia was also the only patient with early CAR-T failure. Future plans include exploration of [18F]FAZA in a more selected patient population.

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Fig. 1

Data availability

Data are available upon reasonable request by emailing the corresponding author (rahul.banerjee.md@gmail.com).

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Acknowledgements

The authors also acknowledge the staff at the UCSF China Basin Imaging Center. Most importantly, the authors acknowledge the patients who participated in this study.

Funding

The authors acknowledge funding through a UCSF RAP Pilot Award (awardee: CBA), NCI K08CA249744 (awardee: VW), and ASCO Conquer Cancer Foundation Career Development Award (awardee: VW).

Author information

Author notes

  1. Rahul Banerjee and Victoria Wang contributed equally to this study.

Authors and Affiliations

  1. Division of Medical Oncology, Department of Medicine, University of Washington, 825 Eastlake Ave E, LG-650, Seattle, WA, 98109, USA

    Rahul Banerjee

  2. Division of Hematology and Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA

    Victoria Wang, Divita Pandita, Michelle K. Leonard, Siobhan LaRue, Lawrence Kaplan, Weiyun Z. Ai, Bita Fakhri, Michael Spinner, Madhav Rao Seshadri & Charalambos Babis Andreadis

  3. Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA

    Chiung-Yu Huang

  4. Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA

    Michael Ahmadi & Miguel Hernandez Pampaloni

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  1. Rahul Banerjee
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Contributions

RB: study design, data collection, data interpretation, manuscript writing, approval of final manuscript; VW: data collection, data interpretation, manuscript writing, approval of final manuscript; CYH: study design, data interpretation, manuscript review, approval of final manuscript; DP: data collection, data interpretation, manuscript writing, approval of final manuscript; MKL: manuscript review, approval of final manuscript; SL: data collection, manuscript review, approval of final manuscript; MA: data collection, manuscript review, approval of final manuscript; LK: manuscript review, approval of final manuscript; WZA: manuscript review, approval of final manuscript; BF: manuscript review, approval of final manuscript; MS: manuscript review, approval of final manuscript; MRS: manuscript review, approval of final manuscript; MHP: study design, data interpretation, manuscript review, approval of final manuscript; CBA: study design, data collection, data interpretation, manuscript writing, approval of final manuscript.

Corresponding author

Correspondence to Rahul Banerjee.

Ethics declarations

Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. Our study was reviewed and approved by the University of California San Francisco Institutional Review Board. Informed consent was obtained from all individual participants included in the study. The authors affirm that human research participants provided informed consent for the publication of the images in Fig. 1.

Competing interests

RB: Consulting: BMS, Caribou Biosciences, Genentech, Janssen, Pfizer, Sanofi, SparkCures; research support: Pack Health. VW: Research support: Inhibrx. WZA: Consulting: Kite, ADC, More Health, Secura Bio, Kyowa. BF: Consulting: Abbvie, Adaptive, AstraZeneca, BeiGene, BMS, CurioScience, Genentech, Genmab, Loxo/Lilly, Medscape, Pharmacyclics, TG Therapeutics; Research support: Abbvie, BMS, Genmab, Loxo/Lilly. MS: Consulting: Gilead, Kite. MRS: Consulting: Beigene, Gilead; research support: Eli Lilly, Roche. CA: Consulting: BMS, Gilead; Research support: BMS, Novartis. Remaining authors: none.

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Banerjee, R., Wang, V., Huang, CY. et al. Hypoxia-specific imaging in patients with lymphoma undergoing CAR-T therapy. Eur J Nucl Med Mol Imaging 50, 3349–3353 (2023). https://doi.org/10.1007/s00259-023-06296-z

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  • DOI: https://doi.org/10.1007/s00259-023-06296-z

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