Multicenter development of a PET-based risk assessment tool for product-specific outcome prediction in large B-cell lymphoma patients undergoing CAR T-cell therapy.

Autor: Voltin CA; Department of Nuclear Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany. conrad-amadeus.voltin@uk-koeln.de., Paccagnella A; Department of Experimental, Diagnostic, and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy., Winkelmann M; Department of Radiology, University Hospital Munich, Ludwig Maximilian University Munich, Munich, Germany., Heger JM; Department of Internal Medicine I, Center for Integrated Oncology Aachen-Bonn-Cologne-Düsseldorf (CIO ABCD), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.; Cologne Lymphoma Working Group (CLWG), Cologne, Germany., Casadei B; Department of Experimental, Diagnostic, and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.; 'L. e A. Seràgnoli' Institute of Hematology, Scientific Institute for Research, Hospitalization, and Healthcare (IRCCS) 'Azienda Ospedaliero-Universitaria Di Bologna', University of Bologna, Bologna, Italy., Beckmann L; Department of Internal Medicine I, Center for Integrated Oncology Aachen-Bonn-Cologne-Düsseldorf (CIO ABCD), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany., Herrmann K; Department of Nuclear Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.; German Cancer Consortium (DKTK) Partner Site Essen/Düsseldorf, Essen, Germany., Dekorsy FJ; Department of Nuclear Medicine, University Hospital Munich, Ludwig Maximilian University Munich, Munich, Germany., Kutsch N; Department of Internal Medicine I, Center for Integrated Oncology Aachen-Bonn-Cologne-Düsseldorf (CIO ABCD), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.; Cologne Lymphoma Working Group (CLWG), Cologne, Germany., Borchmann P; Department of Internal Medicine I, Center for Integrated Oncology Aachen-Bonn-Cologne-Düsseldorf (CIO ABCD), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.; Cologne Lymphoma Working Group (CLWG), Cologne, Germany., Fanti S; Department of Experimental, Diagnostic, and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.; Division of Nuclear Medicine, Scientific Institute for Research, Hospitalization, and Healthcare (IRCCS) 'Azienda Ospedaliero-Universitaria Di Bologna', University of Bologna, Bologna, Italy., Kunz WG; Department of Radiology, University Hospital Munich, Ludwig Maximilian University Munich, Munich, Germany., Subklewe M; Department of Medicine III, Comprehensive Cancer Center Munich (CCCM), University Hospital Munich, Ludwig Maximilian University Munich, Munich, Germany.; Laboratory for Translational Cancer Immunology, Gene Center Munich, Ludwig Maximilian University Munich, Munich, Germany.; German Cancer Consortium (DKTK) and Bavarian Center for Cancer Research (BZKF) Partner Site Munich, Munich, Germany., Kobe C; Department of Nuclear Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany., Zinzani PL; Department of Experimental, Diagnostic, and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.; 'L. e A. Seràgnoli' Institute of Hematology, Scientific Institute for Research, Hospitalization, and Healthcare (IRCCS) 'Azienda Ospedaliero-Universitaria Di Bologna', University of Bologna, Bologna, Italy., Stelljes M; Department of Medicine A-Hematology, Oncology, and Pneumology, West German Cancer Center (WTZ) Network Partner Site, University Hospital Münster, University of Münster, Münster, Germany., Roth KS; Department of Nuclear Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany., Drzezga A; Department of Nuclear Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany., Noppeney R; German Cancer Consortium (DKTK) Partner Site Essen/Düsseldorf, Essen, Germany.; Department of Hematology and Stem Cell Transplantation, West German Cancer Center (WTZ), University Hospital Essen, University of Duisburg-Essen, Essen, Germany., Rahbar K; Department of Nuclear Medicine, University Hospital Münster, University of Münster, Münster, Germany., Reinhardt HC; German Cancer Consortium (DKTK) Partner Site Essen/Düsseldorf, Essen, Germany.; Department of Hematology and Stem Cell Transplantation, West German Cancer Center (WTZ), University Hospital Essen, University of Duisburg-Essen, Essen, Germany., von Tresckow B; German Cancer Consortium (DKTK) Partner Site Essen/Düsseldorf, Essen, Germany.; Department of Hematology and Stem Cell Transplantation, West German Cancer Center (WTZ), University Hospital Essen, University of Duisburg-Essen, Essen, Germany., Seifert R; Department of Nuclear Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.; German Cancer Consortium (DKTK) Partner Site Essen/Düsseldorf, Essen, Germany.; Department of Nuclear Medicine, University Hospital Münster, University of Münster, Münster, Germany., Albring JC; Department of Medicine A-Hematology, Oncology, and Pneumology, West German Cancer Center (WTZ) Network Partner Site, University Hospital Münster, University of Münster, Münster, Germany., Blumenberg V; Department of Medicine III, Comprehensive Cancer Center Munich (CCCM), University Hospital Munich, Ludwig Maximilian University Munich, Munich, Germany.; Laboratory for Translational Cancer Immunology, Gene Center Munich, Ludwig Maximilian University Munich, Munich, Germany.; German Cancer Consortium (DKTK) and Bavarian Center for Cancer Research (BZKF) Partner Site Munich, Munich, Germany., Farolfi A; Division of Nuclear Medicine, Scientific Institute for Research, Hospitalization, and Healthcare (IRCCS) 'Azienda Ospedaliero-Universitaria Di Bologna', University of Bologna, Bologna, Italy., Flossdorf S; Institute for Medical Informatics, Biometry, and Epidemiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany., Gödel P; Department of Internal Medicine I, Center for Integrated Oncology Aachen-Bonn-Cologne-Düsseldorf (CIO ABCD), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.; Cologne Lymphoma Working Group (CLWG), Cologne, Germany., Hanoun C; German Cancer Consortium (DKTK) Partner Site Essen/Düsseldorf, Essen, Germany.; Department of Hematology and Stem Cell Transplantation, West German Cancer Center (WTZ), University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Jazyk: angličtina
Zdroj: European journal of nuclear medicine and molecular imaging [Eur J Nucl Med Mol Imaging] 2024 Apr; Vol. 51 (5), pp. 1361-1370. Date of Electronic Publication: 2023 Dec 20.
DOI: 10.1007/s00259-023-06554-0
Abstrakt: Purpose: The emergence of chimeric antigen receptor (CAR) T-cell therapy fundamentally changed the management of individuals with relapsed and refractory large B-cell lymphoma (LBCL). However, real-world data have shown divergent outcomes for the approved products. The present study therefore set out to evaluate potential risk factors in a larger cohort.
Methods: Our analysis set included 88 patients, treated in four German university hospitals and one Italian center, who had undergone 2-[ 18 F]fluoro-2-deoxy-D-glucose positron emission tomography (PET) before CAR T-cell therapy with tisagenlecleucel or axicabtagene ciloleucel. We first determined the predictive value of conventional risk factors, treatment lines, and response to bridging therapy for progression-free survival (PFS) through forward selection based on Cox regression. In a second step, the additive potential of two common PET parameters was assessed. Their optimal dichotomizing thresholds were calculated individually for each CAR T-cell product.
Results: Extra-nodal involvement emerged as the most relevant of the conventional tumor and patient characteristics. Moreover, we found that inclusion of metabolic tumor volume (MTV) further improves outcome prediction. The hazard ratio for a PFS event was 1.68 per unit increase of our proposed risk score (95% confidence interval [1.20, 2.35], P = 0.003), which comprised both extra-nodal disease and lymphoma burden. While the most suitable MTV cut-off among patients receiving tisagenlecleucel was 11 mL, a markedly higher threshold of 259 mL showed optimal predictive performance in those undergoing axicabtagene ciloleucel treatment.
Conclusion: Our analysis demonstrates that the presence of more than one extra-nodal lesion and higher MTV in LBCL are associated with inferior outcome after CAR T-cell treatment. Based on an assessment tool including these two factors, patients can be assigned to one of three risk groups. Importantly, as shown by our study, metabolic tumor burden might facilitate CAR T-cell product selection and reflect the individual need for bridging therapy.
(© 2023. The Author(s).)
Databáze: MEDLINE
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