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Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging 3/2022

04.09.2021 | Original Article

[18F]FDG PET-CT in patients with DLBCL treated with CAR-T cell therapy: a practical approach of reporting pre- and post-treatment studies

verfasst von: Dan Cohen, Efrat Luttwak, Ofrat Beyar-Katz, Shir Hazut Krauthammer, Yael Bar-On, Odelia Amit, Ronit Gold, Chava Perry, Irit Avivi, Ron Ram, Einat Even-Sapir

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 3/2022

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Abstract

Purpose

The introduction of CD19-specific chimeric antigen receptor T-cell therapy (CAR-T) for treatment of relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL) gives hope to patients with otherwise dismal prognosis. Therapy outcomes, however, depend upon selection of patients and accurate early identification of non-responders. Patients treated with CAR-T usually undergo [18F]FDG PET-CT at time of decision (TD), time of CAR-T transfusion (TT), 1 month (M1), and 3 months (M3) post-therapy. The purpose of the current study was to identify the specific parameters that should be addressed when reporting PET-CT studies in the clinical setting of CAR-T therapy.

Methods

A total of 138 PET-CT scans (30 TD, 42 TT, 44 M1, 22 M3) of 48 patients treated with CAR-T were included. SUVmax, TMTV, and TLG were calculated in all scans. Response was assessed using the Deauville scale and ΔSUVmax method. Overall survival (OS) was the primary endpoint. Median follow-up was 12.8 (IQR 6.4–16.0) months from CAR-T infusion.

Results

In a univariate analysis, TD-SUVmax > 17.1 and TT-SUVmax > 12.1 were associated with shorter OS (Pv < 0.05). In a multivariate analysis, three factors were significantly associated with shorter OS: TD-SUVmax > 17.1 (HR 10.3; Pv < 0.01), LDH > 450 U/l (HR 7.7; Pv < 0.01), and ECOG score > 1 (HR 5.5; Pv = 0.04). Data from TD and TT PET-CT scans were not predictive of toxicity. On M1-PET-CT, patients with a Deauville score > 3 had significantly shorter OS (median 7.9 months, versus not reached, Pv < 0.01). ΔSUVmax ≤ 66% on M1-PET-CT predicted shorter OS when M1-SUVmax was compared to TD-SUVmax (Pv = 0.02) but not to TT-SUVmax (Pv = 0.38).

Conclusion

Pre-treatment SUVmax may guide patient selection for CAR-T therapy. On M1-PET-CT, Deauville score and ΔSUVmax from TD may identify early therapy failure. These parameters are easy to obtain and should be included in the PET-CT report.
Literatur
1.
Zurück zum Zitat Van Den Neste E, Schmitz N, Mounier N, Gill D, Linch D, Trneny M, Milpied N, Radford J, Ketterer N, Shpilberg O, Dührsen U. Outcome of patients with relapsed diffuse large B-cell lymphoma who fail second-line salvage regimens in the International CORAL study. Bone Marrow Transplant. 2016;51(1):51–7. https://doi.org/10.1038/bmt.2015.213.CrossRef Van Den Neste E, Schmitz N, Mounier N, Gill D, Linch D, Trneny M, Milpied N, Radford J, Ketterer N, Shpilberg O, Dührsen U. Outcome of patients with relapsed diffuse large B-cell lymphoma who fail second-line salvage regimens in the International CORAL study. Bone Marrow Transplant. 2016;51(1):51–7. https://​doi.​org/​10.​1038/​bmt.​2015.​213.CrossRef
2.
3.
Zurück zum Zitat Locke FL, Ghobadi A, Jacobson CA, Miklos DB, Lekakis LJ, Oluwole OO, Lin Y, Braunschweig I, Hill BT, Timmerman JM, Deol A. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1–2 trial. Lancet Oncol. 2019;20(1):31–42. https://doi.org/10.1016/S1470-2045(18)30864-7.CrossRefPubMed Locke FL, Ghobadi A, Jacobson CA, Miklos DB, Lekakis LJ, Oluwole OO, Lin Y, Braunschweig I, Hill BT, Timmerman JM, Deol A. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1–2 trial. Lancet Oncol. 2019;20(1):31–42. https://​doi.​org/​10.​1016/​S1470-2045(18)30864-7.CrossRefPubMed
10.
Zurück zum Zitat Dührsen U, Müller S, Hertenstein B, Thomssen H, Kotzerke J, Mesters R, Berdel WE, Franzius C, Kroschinsky F, Weckesser M, Kofahl-Krause D. Positron emission tomography-guided therapy of aggressive non-Hodgkin lymphomas (PETAL): a multicenter, randomized phase III trial. J Clin Oncol. 2018;36(20):2024–34. https://doi.org/10.1200/JCO.2017.76.8093.CrossRefPubMed Dührsen U, Müller S, Hertenstein B, Thomssen H, Kotzerke J, Mesters R, Berdel WE, Franzius C, Kroschinsky F, Weckesser M, Kofahl-Krause D. Positron emission tomography-guided therapy of aggressive non-Hodgkin lymphomas (PETAL): a multicenter, randomized phase III trial. J Clin Oncol. 2018;36(20):2024–34. https://​doi.​org/​10.​1200/​JCO.​2017.​76.​8093.CrossRefPubMed
11.
Zurück zum Zitat Burggraaff CN, de Jong A, Hoekstra OS, Hoetjes NJ, Nievelstein RA, Jansma EP, Heymans MW, de Vet HC, Zijlstra JM. Predictive value of interim positron emission tomography in diffuse large B-cell lymphoma: a systematic review and meta-analysis. Eur J Nucl Med Mol Imaging. 2019;46(1):65–79. https://doi.org/10.1007/s00259-018-4103-3.CrossRefPubMed Burggraaff CN, de Jong A, Hoekstra OS, Hoetjes NJ, Nievelstein RA, Jansma EP, Heymans MW, de Vet HC, Zijlstra JM. Predictive value of interim positron emission tomography in diffuse large B-cell lymphoma: a systematic review and meta-analysis. Eur J Nucl Med Mol Imaging. 2019;46(1):65–79. https://​doi.​org/​10.​1007/​s00259-018-4103-3.CrossRefPubMed
13.
Zurück zum Zitat Pregno P, Chiappella A, Bello M, Botto B, Ferrero S, Franceschetti S, Giunta F, Ladetto M, Limerutti G, Menga M, Nicolosi M. Interim 18-FDG-PET/CT failed to predict the outcome in diffuse large B-cell lymphoma patients treated at the diagnosis with rituximab-CHOP. Blood J Am Soc Hematol. 2012;119(9):2066–73. https://doi.org/10.1182/blood-2011-06-359943.CrossRef Pregno P, Chiappella A, Bello M, Botto B, Ferrero S, Franceschetti S, Giunta F, Ladetto M, Limerutti G, Menga M, Nicolosi M. Interim 18-FDG-PET/CT failed to predict the outcome in diffuse large B-cell lymphoma patients treated at the diagnosis with rituximab-CHOP. Blood J Am Soc Hematol. 2012;119(9):2066–73. https://​doi.​org/​10.​1182/​blood-2011-06-359943.CrossRef
14.
Zurück zum Zitat González-Barca E, Canales M, Cortés M, Vidal MJ, Salar A, Oriol A, Bargay J, Bello JL, Sánchez JJ, Tomás JF, Donato E. Predictive value of interim 18F-FDG-PET/CT for event-free survival in patients with diffuse large B-cell lymphoma homogenously treated in a phase II trial with six cycles of R-CHOP-14 plus pegfilgrastim as first-line treatment. Nucl Med Commun. 2013;34(10):946–52. https://doi.org/10.1097/MNM.0b013e328363c695.CrossRefPubMed González-Barca E, Canales M, Cortés M, Vidal MJ, Salar A, Oriol A, Bargay J, Bello JL, Sánchez JJ, Tomás JF, Donato E. Predictive value of interim 18F-FDG-PET/CT for event-free survival in patients with diffuse large B-cell lymphoma homogenously treated in a phase II trial with six cycles of R-CHOP-14 plus pegfilgrastim as first-line treatment. Nucl Med Commun. 2013;34(10):946–52. https://​doi.​org/​10.​1097/​MNM.​0b013e328363c695​.CrossRefPubMed
15.
Zurück zum Zitat Zhu Y, Lu J, Wei X, Song S, Huang G. The predictive value of interim and final [18F] fluorodeoxyglucose positron emission tomography after rituximab-chemotherapy in the treatment of non-Hodgkin’s lymphoma: a meta-analysis. Biomed Res Int. 2013;1:2013. https://doi.org/10.1155/2013/275805.CrossRef Zhu Y, Lu J, Wei X, Song S, Huang G. The predictive value of interim and final [18F] fluorodeoxyglucose positron emission tomography after rituximab-chemotherapy in the treatment of non-Hodgkin’s lymphoma: a meta-analysis. Biomed Res Int. 2013;1:2013. https://​doi.​org/​10.​1155/​2013/​275805.CrossRef
16.
Zurück zum Zitat Mamot C, Klingbiel D, Hitz F, Renner C, Pabst T, Driessen C, Mey U, Pless M, Bargetzi M, Krasniqi F, Gigli F. Final results of a prospective evaluation of the predictive value of interim positron emission tomography in patients with diffuse large B-cell lymphoma treated with R-CHOP-14 (SAKK 38/07). J Clin Oncol. 2015;33(23):2523–9. https://doi.org/10.1200/JCO.2014.58.9846.CrossRefPubMed Mamot C, Klingbiel D, Hitz F, Renner C, Pabst T, Driessen C, Mey U, Pless M, Bargetzi M, Krasniqi F, Gigli F. Final results of a prospective evaluation of the predictive value of interim positron emission tomography in patients with diffuse large B-cell lymphoma treated with R-CHOP-14 (SAKK 38/07). J Clin Oncol. 2015;33(23):2523–9. https://​doi.​org/​10.​1200/​JCO.​2014.​58.​9846.CrossRefPubMed
18.
Zurück zum Zitat Rekowski J, Hüttmann A, Schmitz C, Müller SP, Kurch L, Kotzerke J, Franzius C, Weckesser M, Bengel FM, Freesmeyer M, Hertel A. Interim PET evaluation in diffuse large B-cell lymphoma employing published recommendations: comparison of the Deauville 5-point scale and the ΔSUVmax method. J Nucl Med. 2020. https://doi.org/10.2967/jnumed.120.244145.CrossRefPubMed Rekowski J, Hüttmann A, Schmitz C, Müller SP, Kurch L, Kotzerke J, Franzius C, Weckesser M, Bengel FM, Freesmeyer M, Hertel A. Interim PET evaluation in diffuse large B-cell lymphoma employing published recommendations: comparison of the Deauville 5-point scale and the ΔSUVmax method. J Nucl Med. 2020. https://​doi.​org/​10.​2967/​jnumed.​120.​244145.CrossRefPubMed
20.
Zurück zum Zitat Wang J, Hu Y, Yang S, Wei G, Zhao X, Wu W, Zhang Y, Zhang Y, Chen D, Wu Z, Xiao L. Role of fluorodeoxyglucose positron emission tomography/computed tomography in predicting the adverse effects of chimeric antigen receptor T cell therapy in patients with non-Hodgkin lymphoma. Biol Blood Marrow Transplant. 2019;25(6):1092–8. https://doi.org/10.1016/j.bbmt.2019.02.008.CrossRefPubMed Wang J, Hu Y, Yang S, Wei G, Zhao X, Wu W, Zhang Y, Zhang Y, Chen D, Wu Z, Xiao L. Role of fluorodeoxyglucose positron emission tomography/computed tomography in predicting the adverse effects of chimeric antigen receptor T cell therapy in patients with non-Hodgkin lymphoma. Biol Blood Marrow Transplant. 2019;25(6):1092–8. https://​doi.​org/​10.​1016/​j.​bbmt.​2019.​02.​008.CrossRefPubMed
21.
Zurück zum Zitat Iacoboni G, Simó M, Villacampa G, Catalá E, Carpio C, Díaz-Lagares C, Vidal-Jordana Á, Bobillo S, Marín-Niebla A, Pérez A, Jiménez M. Prognostic impact of total metabolic tumor volume in large B-cell lymphoma patients receiving CAR T-cell therapy. Ann Hematol. 2021;8:1–8. https://doi.org/10.1007/s00277-021-04560-6.CrossRef Iacoboni G, Simó M, Villacampa G, Catalá E, Carpio C, Díaz-Lagares C, Vidal-Jordana Á, Bobillo S, Marín-Niebla A, Pérez A, Jiménez M. Prognostic impact of total metabolic tumor volume in large B-cell lymphoma patients receiving CAR T-cell therapy. Ann Hematol. 2021;8:1–8. https://​doi.​org/​10.​1007/​s00277-021-04560-6.CrossRef
22.
Zurück zum Zitat Shah NN, Nagle SJ, Torigian DA, Farwell MD, Hwang WT, Frey N, Nasta SD, Landsburg D, Mato A, June CH, Schuster SJ. Early positron emission tomography/computed tomography as a predictor of response after CTL019 chimeric antigen receptor–T-cell therapy in B-cell non-Hodgkin lymphomas. Cytotherapy. 2018;20(12):1415–8. https://doi.org/10.1016/j.jcyt.2018.10.003.CrossRefPubMed Shah NN, Nagle SJ, Torigian DA, Farwell MD, Hwang WT, Frey N, Nasta SD, Landsburg D, Mato A, June CH, Schuster SJ. Early positron emission tomography/computed tomography as a predictor of response after CTL019 chimeric antigen receptor–T-cell therapy in B-cell non-Hodgkin lymphomas. Cytotherapy. 2018;20(12):1415–8. https://​doi.​org/​10.​1016/​j.​jcyt.​2018.​10.​003.CrossRefPubMed
23.
Zurück zum Zitat Derlin T, Schultze-Florey C, Werner RA, Möhn N, Skripuletz T, David S, Beutel G, Eder M, Ross TL, Bengel FM, Ganser A. 18 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. Ann Nucl Med. 2021;35(1):132–8. https://doi.org/10.1007/s12149-020-01544-w.CrossRefPubMed Derlin T, Schultze-Florey C, Werner RA, Möhn N, Skripuletz T, David S, Beutel G, Eder M, Ross TL, Bengel FM, Ganser A. 18 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. Ann Nucl Med. 2021;35(1):132–8. https://​doi.​org/​10.​1007/​s12149-020-01544-w.CrossRefPubMed
25.
26.
Zurück zum Zitat Casasnovas RO, Meignan M, Berriolo-Riedinger A, Bardet S, Julian A, Thieblemont C, Vera P, Bologna S, Brière J, Jais JP, Haioun C. SUVmax reduction improves early prognosis value of interim positron emission tomography scans in diffuse large B-cell lymphoma. Blood J Am Soc Hematol. 2011;118(1):37–43. https://doi.org/10.1182/blood-2010-12-327767.CrossRef Casasnovas RO, Meignan M, Berriolo-Riedinger A, Bardet S, Julian A, Thieblemont C, Vera P, Bologna S, Brière J, Jais JP, Haioun C. SUVmax reduction improves early prognosis value of interim positron emission tomography scans in diffuse large B-cell lymphoma. Blood J Am Soc Hematol. 2011;118(1):37–43. https://​doi.​org/​10.​1182/​blood-2010-12-327767.CrossRef
29.
30.
Zurück zum Zitat Hirayama AV, Gauthier J, Hay KA, Voutsinas JM, Wu Q, Gooley T, Li D, Cherian S, Chen X, Pender BS, Hawkins RM. The response to lymphodepletion impacts PFS in patients with aggressive non-Hodgkin lymphoma treated with CD19 CAR T cells. Blood J Am Soc Hematol. 2019;133(17):1876–87. https://doi.org/10.1182/blood-2018-11-887067.CrossRef Hirayama AV, Gauthier J, Hay KA, Voutsinas JM, Wu Q, Gooley T, Li D, Cherian S, Chen X, Pender BS, Hawkins RM. The response to lymphodepletion impacts PFS in patients with aggressive non-Hodgkin lymphoma treated with CD19 CAR T cells. Blood J Am Soc Hematol. 2019;133(17):1876–87. https://​doi.​org/​10.​1182/​blood-2018-11-887067.CrossRef
Metadaten
Titel
[18F]FDG PET-CT in patients with DLBCL treated with CAR-T cell therapy: a practical approach of reporting pre- and post-treatment studies
verfasst von
Dan Cohen
Efrat Luttwak
Ofrat Beyar-Katz
Shir Hazut Krauthammer
Yael Bar-On
Odelia Amit
Ronit Gold
Chava Perry
Irit Avivi
Ron Ram
Einat Even-Sapir
Publikationsdatum
04.09.2021
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 3/2022
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-021-05551-5

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