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18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Following Chimeric Antigen Receptor T-cell Therapy in Large B-cell Lymphoma

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Abstract

Purpose

18F-Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) is a well-established imaging modality to assess responses in patients with B-cell neoplasms. However, there is limited information about the utility of FDG PET/CT after chimeric antigen receptor T-cell (CART) therapies for large B-cell lymphomas. In this retrospective analysis, we aimed to evaluate how FDG PET/CT performs in patients receiving commercially available anti-CD19 CART therapies for relapsed/refractory (r/r) large B-cell lymphomas. In addition, we examined the time to repeat scan and the rate of pseudoprogression within this population. Lastly, the rates of radiographic response to CART therapy using FDG PET/CT are reported.

Procedures

The pre-treatment and post-treatment scans were analyzed from a selected cohort of 43 patients from a single institution. Patients were stratified by diagnosis of either a first occurrence of diffuse large B-cell lymphoma: de novo diffuse large B-cell lymphoma (DLBCL); or a transformed diffuse large B-cell lymphoma arising from indolent non-Hodgkin lymphoma (t-iNHL).

Results

More patients received CART therapy for DLBCL than t-iNHL (65 % vs 35 %). FDG PET/CT had a 99 % sensitivity and 100 % specificity for detecting recurrent disease in this group. The median time to initial response assessment was 86 days (IQR 79–91; full range 24–146) after infusion. There were no biopsy-proven cases of pseudoprogression identified. In this selected group of patients, the overall response rate by Lugano 2014 criteria was 56 %. All patients with a partial response (N = 6) eventually progressed despite additional therapy.

Conclusions

Due to its excellent test characteristics and ability to detect asymptomatic disease, routine surveillance with PET/CT at 3 months after CART infusion is supported by our data. Earlier PET/CT may be of value in select situations as we did not find any cases of pseudoprogression.

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Acknowledgements

MAS is supported by the NIH Office of the Director Early Independence Award (DP5-OD26386), Burroughs Wellcome Fund Career Award for Medical Scientists. Editorial assistance was provided by David A. Mankoff, MD, PhD. Biorender was used to generate figures and schemes.

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Authors and Affiliations

  1. Department of Radiology, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Andrew Ruff, Austin R. Pantel, Michael D. Farwell & Mark A. Sellmyer

  2. Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Hatcher J. Ballard, Esin C. Namoglu, Mitchell E. Hughes, Sunita D. Nasta, Elise A. Chong, Marco Ruella & Jakub Svoboda

  3. Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Adam Bagg

  4. Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA

    Marco Ruella

  5. Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA, USA

    Mark A. Sellmyer

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  1. Andrew Ruff
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Contributions

Conception and design: A. Ruff, A.R. Pantel, M.D. Farwell, J. Svoboda, and M.A. Sellmyer

Development of methodology: A. Ruff, A.R. Pantel, M.A. Sellmyer

Acquisition of data: A. Ruff, H.J. Ballard, J. Svoboda

Analysis and interpretation of data: A. Ruff, H.J. Ballard, A. Bagg, A.R. Pantel, J. Svoboda, M.A. Sellmyer

Reviewed PET/CT Scans: A. Ruff, A.R. Pantel, M.A. Sellmyer

Writing, review, and/or revision of the manuscript: A. Ruff wrote the initial draft. All authors contributed to the final manuscript.

Administrative, technical, or material support (i.e., reporting or organizing data, constructing databases): A. Ruff, H.J. Ballard

Study supervision: J. Svoboda and M.A. Sellmyer

Corresponding authors

Correspondence to Jakub Svoboda or Mark A. Sellmyer.

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Conflict of Interest

AR: none. HJB: none. ARP: none. ECN: none. MEH: AstraZeneca, Genzyme, Janssen, AbbVie: consultancy; Acerta Pharma, HOPA: research Support. SDN: Roche, Rafael, Forty Seven, Pharmacyclics, Incyte, Debiopharm, Aileron: research support; Morphosys: honorarium. EAC: Novartis, BMS, KITE: advisory boards. AB: none. MR: BMS, NanoString: consultancy; UPenn/Novartis: patents and royalties; Abclon: consultancy, research funding. MDF: none. JS: Genmab, Adaptive, Imbrium, Atara: consultancy; Incyte, Merck: research funding; AstraZeneca, BMS, Pharmacyclics, Seattle Genetics: consultancy, research funding; TG: research funding. MAS: co-founder of Vellum Biosciences, which is supporting the development and commercialization of radiotracers to monitor gene and cell therapies.

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Ruff, A., Ballard, H.J., Pantel, A.R. et al. 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Following Chimeric Antigen Receptor T-cell Therapy in Large B-cell Lymphoma. Mol Imaging Biol 23, 818–826 (2021). https://doi.org/10.1007/s11307-021-01627-8

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