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. 2022 Mar 10;11(6):1522.
doi: 10.3390/jcm11061522.

Value of CT-Textural Features and Volume-Based PET Parameters in Comparison to Serologic Markers for Response Prediction in Patients with Diffuse Large B-Cell Lymphoma Undergoing CD19-CAR-T Cell Therapy

Christian Philipp Reinert  1 , Regine Mariette Perl  1 , Christoph Faul  2 , Claudia Lengerke  2 , Konstantin Nikolaou  1   3 , Helmut Dittmann  4 , Wolfgang A Bethge  2 , Marius Horger  1
Affiliations

Value of CT-Textural Features and Volume-Based PET Parameters in Comparison to Serologic Markers for Response Prediction in Patients with Diffuse Large B-Cell Lymphoma Undergoing CD19-CAR-T Cell Therapy

Christian Philipp Reinert et al. J Clin Med. .

Abstract

The goal of this study was to investigate the value of CT-textural features and volume-based PET parameters in comparison to serologic markers for response prediction in patients with diffuse large B-cell lymphoma (DLBCL) undergoing cluster of differentiation (CD19)-chimeric antigen receptor (CAR)-T cell therapy. We retrospectively analyzed the whole-body (WB)-metabolic tumor volume (MTV), the WB-total lesion glycolysis (TLG) and first order textural features derived from 18F-FDG-PET/CT, as well as serologic parameters (C-reactive protein [CRP] and lactate dehydrogenase [LDH], leucocytes) prior and after CAR-T cell therapy in 21 patients with DLBCL (57.7 ± 14.7 year; 7 female). Interleukin 6 (IL-6) and IL-2 receptor peaks were monitored after treatment onset and compared with patient outcome judged by follow-up 18F-FDG-PET/CT. In 12/21 patients (57%), complete remission (CR) was observed, whereas 9/21 patients (43%) showed partial remission (PR). At baseline, WB-MTV and WB-TLG were lower in patients achieving CR (35 ± 38 mL and 319 ± 362) compared to patients achieving PR (88 ± 110 mL and 1487 ± 2254; p < 0.05). The “entropy” proved lower (1.81 ± 0.09) and “uniformity” higher (0.33 ± 0.02) in patients with CR compared to PR (2.08 ± 0.22 and 0.28 ± 0.47; p < 0.05). Patients achieving CR had lower levels of CRP, LDH and leucocytes at baseline compared to patients achieving PR (p < 0.05). In the entire cohort, WB-MTV and WB-TLG decreased after therapy onset (p < 0.01) becoming not measurable in the CR-group. Leucocytes and CRP significantly dropped after therapy (p < 0.01). The IL-6 and IL-2R peaks after therapy were lower in patients with CR compared to PR (p > 0.05). In conclusion, volume-based PET parameters derived from PET/CT and CT-textural features have the potential to predict therapy response in patients with DLBCL undergoing CAR-T cell therapy.

Keywords: chimeric antigen receptor T cells; computed tomography; diffuse-large B cell lymphoma; positron emission tomography; response assessment; texture analysis.

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Conflict of interest statement

Marius Horger received institutional research funds and speaker’s honorarium from Siemens Healthineers and is a scientific advisor of Siemens Healthcare Germany. The other authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1
(a) At baseline 18F-FDG PET/CT before CAR-T cell therapy, both the whole-body MTV (35 ± 38 mL vs. 88 ± 110 mL) and (b) the whole-body TLG (319 ± 362 vs. 1488 ± 2254) were lower in patients achieving CR compared to patients achieving PR (p < 0.01 and p < 0.05). The asterisk (*) indicates clinical significance (p < 0.05).
Figure 2
Figure 2
(a) Whole-body MTV at baseline 18F-FDG-PET/CT before CAR T cell therapy (62 ± 86 mL) and at first follow-up 18F-FDG-PET/CT (4 ± 5 mL) after CAR T cell therapy in the entire patient cohort (p < 0.01). (b) Whole-body TLG at baseline 18F-FDG-PET/CT before CAR-T cell therapy (925 ± 1722) and at first follow-up 18F-FDG-PET/CT (33 ± 59) after CAR-T cell therapy in the entire patient cohort (p < 0.01). The asterisk (*) indicates clinical significance (p < 0.05).
Figure 3
Figure 3
(a) Entropy at baseline imaging before CAR-T cell therapy in patients achieving CR (1.81 ± 0.1) vs. PR (2.08 ± 0.2; p < 0.05). (b) Uniformity at baseline imaging before CAR-T cell therapy in patients achieving CR (0.33 ± 0.02) vs. PR (0.28 ± 0.47; p < 0.05). The asterisk (*) indicates clinical significance (p < 0.05).
Figure 4
Figure 4
(a) Serum LDH at baseline before CAR-T cell therapy in patients achieving CR (240 ± 28 U/L) vs. patients achieving PR (443 ± 262 U/L; p < 0.05). (b) CRP at baseline before CAR-T cell therapy in patients achieving CR (2.6 ± 4.6 μg/dL) vs. patients achieving PR (4.2 ± 6.6 μg/dL; p < 0.05). The asterisk (*) indicates clinical significance (p < 0.05).
Figure 5
Figure 5
IL-6 peak (867 ± 951 ng/L vs. 9121 ± 11,266 ng/L) and IL-2R peak (2483 ± 1164 U/mL vs. 5548 ± 3949 U/mL) in patients with CR vs. PR (p > 0.05).
See this image and copyright information in PMC

References

    1. Hosen N. CAR T cell therapy. Immunol. Med. 2020;44:69–73. doi: 10.1080/25785826.2020.1796063. - DOI - PubMed
    1. Rovira J., Valera A., Colomo L., Setoain X., Rodríguez S., Martínez-Trillos A., Giné E., Dlouhy I., Magnano L., Gaya A., et al. Prognosis of patients with diffuse large B cell lymphoma not reaching complete response or relapsing after frontline chemotherapy or immunochemotherapy. Ann. Hematol. 2014;94:803–812. doi: 10.1007/s00277-014-2271-1. - DOI - PMC - PubMed
    1. Bishton M., Hughes S.M., Richardson F., James E., Bessell E., Sovani V., Ganatra R., Haynes A.P., McMillan A.K., Fox C.P. Delineating outcomes of patients with diffuse large b cell lymphoma using the national comprehensive cancer network-international prognostic index and positron emission tomography-defined remission status; a population-based analysis. Br. J. Haematol. 2015;172:246–254. doi: 10.1111/bjh.13831. - DOI - PubMed
    1. Gisselbrecht C., Glass B., Mounier N., Gill D.S., Linch D.C., Trneny M., Bosly A., Ketterer N., Shpilberg O., Hagberg H., et al. Salvage Regimens With Autologous Transplantation for Relapsed Large B-Cell Lymphoma in the Rituximab Era. J. Clin. Oncol. 2010;28:4184–4190. doi: 10.1200/JCO.2010.28.1618. - DOI - PMC - PubMed
    1. Neelapu S.S., Locke F.L., Bartlett N.L., Lekakis L.J., Miklos D.B., Jacobson C.A., Braunschweig I., Oluwole O.O., Siddiqi T., Lin Y., et al. Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. N. Engl. J. Med. 2017;377:2531–2544. doi: 10.1056/NEJMoa1707447. - DOI - PMC - PubMed