18 F-FDG PET/CT of off-target lymphoid organs in CD19-targeting chimeric antigen receptor T-cell therapy for relapsed or
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SHORT COMMUNICATION
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F‑FDG PET/CT of off‑target lymphoid organs in CD19‑targeting chimeric antigen receptor T‑cell therapy for relapsed or refractory diffuse large B‑cell lymphoma
Thorsten Derlin1 · Christian Schultze‑Florey2 · Rudolf A. Werner1 · Nora Möhn3 · Thomas Skripuletz3 · Sascha David4 · Gernot Beutel2 · Matthias Eder2 · Tobias L. Ross1 · Frank M. Bengel1 · Arnold Ganser2 · Christian Koenecke2 Received: 2 September 2020 / Accepted: 16 October 2020 © The Author(s) 2020
Abstract Objective The interplay between systemic inflammation, activity of lymphoid organs and lymphoma activity in CD19-targeting chimeric antigen receptor (CAR)-T-cell immunotherapy, and its significance for response and toxicity, is not well defined. Methods Using serial 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT), metabolic parameters of lymphoma and lymphoid organs were analyzed in ten patients receiving Tisagenlecleucel (an autologous CD19 CAR-T cell product) for relapsed or refractory diffuse large B-cell lymphoma. The prevalence and severity of toxicity (e.g., neurotoxicity) were noted. Results Achieving remission required early metabolic response (P = 0.0476). Early suppression of metabolic activity of lymphoid organs (spleen, P = 0.0368; lymph nodes, P = 0.0470) was associated with poor outcome. Lymphoma metabolic activity was significantly higher in patients with neurotoxicity (P = 0.0489). Conclusions Early metabolic changes in lymphoma lesions and off-target lymphoid organs parallel medium-term response to CAR-T-cell therapy. PET can identify patients at risk for severe toxicity. Keywords CAR-T-cell therapy · Lymphoid organs · Outcome · Toxicity · Positron emission tomography
Introduction CD19-targeted chimeric antigen receptor (CAR)-T-cell immunotherapy has shown remarkable efficacy in relapsed and/or refractory (r/r) CD19+ B-cell malignancies including diffuse large B-cell lymphoma (DLBCL) [1]. Of note, Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12149-020-01544-w) contains supplementary material, which is available to authorized users. * Thorsten Derlin Derlin.Thorsten@mh‑hannover.de 1
Department of Nuclear Medicine, Hannover Medical School, Carl‑Neuberg‑Str. 1, 30625 Hannover, Germany
2
Department of Hematology, Hemostasis, Oncology and Stem-Cell Transplantation, Hannover, Germany
3
Department of Neurology, Hannover, Germany
4
Department of Nephrology, Hannover Medical School, Hannover, Germany
CAR-T cells expand in vivo and may persist and induce sustained remissions years after initial therapy [2]. However, a substantial fraction of patients will not respond, or relapse, and the mechanisms leading to CAR-T-cell therapy resistance are not fully understood. Immunological mechanisms may contribute to both resistance and response to CAR-T-cell therapy [2, 3] and also contribute to toxicity. The cytokine release syndrome (CRS) caused by cytokines produced by both activated CAR-T cells and other immun
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