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Prognostic value of the International Metabolic Prognostic Index for lymphoma patients receiving chimeric antigen receptor T-cell therapy

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Abstract

Purpose

Chimeric antigen receptor T-cell therapy (CART) prolongs survival for patients with relapsed/refractory B-cell non-Hodgkin’s lymphoma. The recently introduced International Metabolic Prognostic Index (IMPI) was shown to improve prognostication in the first-line treatment of large B-cell lymphoma. Here, we investigate the prognostic value of the IMPI for progression-free (PFS) and overall survival (OS) in the setting of CD19 CART.

Methods

Consecutively treated patients with baseline 18F-FDG PET/CT imaging and follow-up imaging at 30 days after CART were included. IMPI is composed of age, stage, and metabolic tumor volume (MTV) at baseline and was compared with the International Prognostic Index (IPI). Both indices were grouped into quartiles, as previously described for IPI. In addition, the continuous IMPI was subdivided into tertiaries for better separation of risk groups. Overall response rate (ORR), depth of response (DoR), and PFS were determined based on Lugano criteria. Proportional Cox regression analysis studied association of IMPI and IPI with PFS and OS.

Results

Thirty-nine patients were included. The IPI was 1 in 23%, 2 in 21%, 3 in 26%, 4 in 21%, and 5 in 10% of the patients. IMPIlow risk, IMPIintermediate risk, and IMPIhigh risk patients had 30-day ORR of 69%, 62%, and 62% and 30-day DoR of − 67%, − 66%, and − 54% with a PFS of 187 days, 97 days, and 87 days, respectively. ORR and DoR showed no correlation with lower IMPI (r = 0.065, p = 0.697). Dividing patients into three risk groups showed a significant trend for PFS stratification (p = 0.030), while IPI did not (p = 0.133). Neither IPI nor IMPI yielded a significant association with OS after CART (both p > 0.05).

Conclusion

In the context of CART, the IMPI yielded prognostic value regarding PFS estimation. In contrast with IMPI in the first-line DLBCL setting, we did not observe a significant association of IMPI at baseline with OS after CART.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. June CH, Sadelain M. Chimeric antigen receptor therapy. N Engl J Med. 2018;379:64–73. https://doi.org/10.1056/NEJMra1706169.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, Jager U, Jaglowski S, Andreadis C, Westin JR, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2019;380:45–56. https://doi.org/10.1056/NEJMoa1804980.

    Article  CAS  PubMed  Google Scholar 

  3. Schuster SJ, Svoboda J, Chong EA, Nasta SD, Mato AR, Anak O, Brogdon JL, Pruteanu-Malinici I, Bhoj V, Landsburg D, et al. Chimeric antigen receptor T cells in refractory B-cell lymphomas. N Engl J Med. 2017;377:2545–54. https://doi.org/10.1056/NEJMoa1708566.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377:2531–44. https://doi.org/10.1056/NEJMoa1707447.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Wang M, Munoz J, Goy A, Locke FL, Jacobson CA, Hill BT, Timmerman JM, Holmes H, Jaglowski S, Flinn IW, et al. KTE-X19 CAR T-cell therapy in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2020;382:1331–42. https://doi.org/10.1056/NEJMoa1914347.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ghione P, Palomba ML, Patel AR, Bobillo S, Deighton K, Jacobson CA, Nahas M, Hatswell AJ, Jung AS, Kanters S, et al. Comparative effectiveness of ZUMA-5 (axi-cel) vs SCHOLAR-5 external control in relapsed/refractory follicular lymphoma. Blood. 2022;140:851–60. https://doi.org/10.1182/blood.2021014375.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. International Non-Hodgkin’s Lymphoma Prognostic Factors P. A predictive model for aggressive non-Hodgkin’s lymphoma. N Engl J Med. 1993;329:987–94. https://doi.org/10.1056/NEJM199309303291402.

    Article  Google Scholar 

  8. Bethge WA, Martus P, Schmitt M, Holtick U, Subklewe M, von Tresckow B, Ayuk F, Wagner-Drouet EM, Wulf GG, Marks R, et al. GLA/DRST real-world outcome analysis of CAR-T cell therapies for large B-cell lymphoma in Germany. Blood. 2022. https://doi.org/10.1182/blood.2021015209.

    Article  PubMed  Google Scholar 

  9. Garcia-Recio M, Wudhikarn K, Pennisi M, Alonso-Trillo R, Flynn J, Shouval R, Afuye AO, Silverberg ML, Batlevi CW, Dahi P, et al. The International Prognostic Index is associated with outcomes in diffuse large B cell lymphoma after chimeric antigen receptor T cell therapy. Transplant Cell Ther. 2021;27:233–40. https://doi.org/10.1016/j.jtct.2020.10.022.

    Article  CAS  PubMed  Google Scholar 

  10. Neelapu SS, Dickinson M, Munoz J, Ulrickson ML, Thieblemont C, Oluwole OO, Herrera AF, Ujjani CS, Lin Y, Riedell PA, et al. Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial. Nat Med. 2022. https://doi.org/10.1038/s41591-022-01731-4.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Cottereau AS, Versari A, Loft A, Casasnovas O, Bellei M, Ricci R, Bardet S, Castagnoli A, Brice P, Raemaekers J, et al. Prognostic value of baseline metabolic tumor volume in early-stage Hodgkin lymphoma in the standard arm of the H10 trial. Blood. 2018;131:1456–63. https://doi.org/10.1182/blood-2017-07-795476.

    Article  CAS  PubMed  Google Scholar 

  12. Meignan M, Cottereau AS, Versari A, Chartier L, Dupuis J, Boussetta S, Grassi I, Casasnovas RO, Haioun C, Tilly H, et al. Baseline metabolic tumor volume predicts outcome in high-tumor-burden follicular lymphoma: a pooled analysis of three multicenter studies. J Clin Oncol. 2016;34:3618–26. https://doi.org/10.1200/JCO.2016.66.9440.

    Article  PubMed  Google Scholar 

  13. Albano D, Bosio G, Bianchetti N, Pagani C, Re A, Tucci A, Giubbini R, Bertagna F. Prognostic role of baseline 18F-FDG PET/CT metabolic parameters in mantle cell lymphoma. Ann Nucl Med. 2019;33:449–58. https://doi.org/10.1007/s12149-019-01354-9.

    Article  CAS  PubMed  Google Scholar 

  14. Ceriani L, Gritti G, Cascione L, Pirosa MC, Polino A, Ruberto T, Stathis A, Bruno A, Moccia AA, Giovanella L, et al. SAKK38/07 study: integration of baseline metabolic heterogeneity and metabolic tumor volume in DLBCL prognostic model. Blood Adv. 2020;4:1082–92. https://doi.org/10.1182/bloodadvances.2019001201.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, Lister TA, Alliance AL, Lymphoma G, Eastern Cooperative Oncology G, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014;32:3059–68. https://doi.org/10.1200/JCO.2013.54.8800.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Barrington SF, Mikhaeel NG, Kostakoglu L, Meignan M, Hutchings M, Mueller SP, Schwartz LH, Zucca E, Fisher RI, Trotman J, et al. Role of imaging in the staging and response assessment of lymphoma: consensus of the International Conference on Malignant Lymphomas Imaging Working Group. J Clin Oncol. 2014;32:3048–58. https://doi.org/10.1200/JCO.2013.53.5229.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Mikhaeel NG, Heymans MW, Eertink JJ, de Vet HCW, Boellaard R, Duhrsen U, Ceriani L, Schmitz C, Wiegers SE, Huttmann A, et al. Proposed new dynamic prognostic index for diffuse large B-cell lymphoma: International Metabolic Prognostic Index. J Clin Oncol. 2022. https://doi.org/10.1200/JCO.21.02063. (JCO2102063).

    Article  PubMed  PubMed Central  Google Scholar 

  18. Vercellino L. High total metabolic tumor volume at baseline predicts survival independent of response to therapy. Blood. 2020;135(16):1396–405.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Nioche C, Orlhac F, Boughdad S, Reuze S, Goya-Outi J, Robert C, Pellot-Barakat C, Soussan M, Frouin F, Buvat I. LIFEx: a freeware for radiomic feature calculation in multimodality imaging to accelerate advances in the characterization of tumor heterogeneity. Cancer Res. 2018;78:4786–9. https://doi.org/10.1158/0008-5472.CAN-18-0125.

    Article  CAS  PubMed  Google Scholar 

  20. Tutino F, Puccini G, Linguanti F, Puccini B, Rigacci L, Kovalchuk S, Sciagra R, Berti V. Baseline metabolic tumor volume calculation using different SUV thresholding methods in Hodgkin lymphoma patients: interobserver agreement and reproducibility across software platforms. Nucl Med Commun. 2021;42:284–91. https://doi.org/10.1097/MNM.0000000000001324.

    Article  CAS  PubMed  Google Scholar 

  21. Martin-Saladich Q, Reynes-Llompart G, Sabate-Llobera A, Palomar-Munoz A, Domingo-Domenech E, Cortes-Romera M. Comparison of different automatic methods for the delineation of the total metabolic tumor volume in I-II stage Hodgkin Lymphoma. Sci Rep. 2020;10:12590. https://doi.org/10.1038/s41598-020-69577-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Batlevi CL, Younes A. Surrogate end points in lymphoma. Ann Oncol. 2018;29:1622–3. https://doi.org/10.1093/annonc/mdy219.

    Article  CAS  PubMed  Google Scholar 

  23. Zhu J, Yang Y, Tao J, Wang SL, Chen B, Dai JR, Hu C, Qi SN, Li YX. Association of progression-free or event-free survival with overall survival in diffuse large B-cell lymphoma after immunochemotherapy: a systematic review. Leuk Off J Leuk Soc Am Leuk Res Fund UK. 2020;34:2576–91. https://doi.org/10.1038/s41375-020-0963-1.

    Article  CAS  Google Scholar 

  24. Adams HJ, de Klerk JM, Fijnheer R, Heggelman BG, Dubois SV, Nievelstein RA, Kwee TC. Where does diffuse large B-cell lymphoma relapse? J Comput Assist Tomogr. 2016;40:531–6. https://doi.org/10.1097/RCT.0000000000000395.

    Article  PubMed  Google Scholar 

  25. Figura NB, Robinson TJ, Sim AJ, Wang X, Cao B, Chavez JC, Shah BD, Khimani F, Lazaryan A, Davila M, et al. Patterns and predictors of failure in recurrent or refractory large B-cell lymphomas after chimeric antigen receptor T-cell therapy. Int J Radiat Oncol Biol Phys. 2021. https://doi.org/10.1016/j.ijrobp.2021.06.038.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Rejeski K, Perez A, Iacoboni G, Penack O, Bucklein V, Jentzsch L, Mougiakakos D, Johnson G, Arciola B, Carpio C, et al. The CAR-HEMATOTOX risk-stratifies patients for severe infections and disease progression after CD19 CAR-T in R/R LBCL. J Immunother Cancer. 2022. https://doi.org/10.1136/jitc-2021-004475.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Rejeski K, Perez A, Sesques P, Hoster E, Berger C, Jentzsch L, Mougiakakos D, Frolich L, Ackermann J, Bucklein V, et al. CAR-HEMATOTOX: a model for CAR T-cell-related hematologic toxicity in relapsed/refractory large B-cell lymphoma. Blood. 2021;138:2499–513. https://doi.org/10.1182/blood.2020010543.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Jain MD, Zhao H, Wang X, Atkins R, Menges M, Reid K, Spitler K, Faramand R, Bachmeier C, Dean EA, et al. Tumor interferon signaling and suppressive myeloid cells are associated with CAR T-cell failure in large B-cell lymphoma. Blood. 2021;137:2621–33. https://doi.org/10.1182/blood.2020007445.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47. https://doi.org/10.1016/j.ejca.2008.10.026.

    Article  CAS  PubMed  Google Scholar 

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Funding

The work was supported by funding from the research program “Förderung für Forschung und Lehre (FöFoLe) project number 1147” of the Medical Faculty of Ludwig Maximilian University (LMU) Munich and the Bavarian Cancer Research Center (BZKF) to M.W. The work was further supported by the Else-Kröner-Fresenius Stiftung (to V.B.) and the German Cancer Consortium DKTK (to V.B.).

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Authors and Affiliations

  1. Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany

    Michael Winkelmann, Marcus Unterrainer, Jens Ricke & Wolfgang G. Kunz

  2. Laboratory for Translational Cancer Immunology, Gene Center of the LMU Munich, Munich, Germany

    Viktoria Blumenberg, Kai Rejeski, Veit L. Bücklein & Marion Subklewe

  3. German Cancer Consortium (DKTK) and Bavarian Center for Cancer Research (BZKF), Partner Site Munich, Munich, Germany

    Viktoria Blumenberg, Kai Rejeski, Veit L. Bücklein & Marion Subklewe

  4. Department of Medicine III, University Hospital, LMU Munich, Munich, Germany

    Viktoria Blumenberg, Kai Rejeski, Veit L. Bücklein, Michael Ruzicka, Christian Schmidt, Michael von Bergwelt-Baildon & Marion Subklewe

  5. Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany

    Franziska J. Dekorsy & Peter Bartenstein

  6. Comprehensive Cancer Center München-LMU (CCCMLMU), LMU Munich, Munich, Germany

    Peter Bartenstein, Jens Ricke, Michael von Bergwelt-Baildon & Wolfgang G. Kunz

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  1. Michael Winkelmann
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Contributions

M.W. and W.G.K. conceived and design the study; V.B., K.R., V.L.B., M.R., M.U., and C.S. collected the data; M.W., V.B., K.R., V.L.B., and W.G.K. analyzed and interpreted the data; and M.W. and W.G.K. drafted the manuscript; and V.B., K.R., F.J.D., P.B., J.R., M.v.B.-B., and M.S. revised the manuscript.

Corresponding author

Correspondence to Wolfgang G. Kunz.

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Ethics approval

All medical records and imaging studies were reviewed with the approval of the LMU Munich Institutional Review Board (LMU Ethics Committee, project number 19–817).

Consent to participate

Informed consent was obtained from all individual participants included in the study.

Competing interests

V.B. has received industry research support from Gilead, Novartis, Celgene, and Roche. K.R. declares having received research funding and travel support from Kite/Gilead and honoraria from Novartis. C.S. received travel support from Kite/Gilead. M.v.B.-B. received research funding and honoraria from Novartis, Kite Pharma, Miltenyi Biotec, Mologen, MSD, Astellas, and Roche. M.S. received industry research support from Amgen, Gilead, Miltenyi Biotec, MorphoSys, Roche, and Seattle Genetics; served as a consultant or advisor to Amgen, Bristol Myers Squibb, Celgene, Gilead, Pfizer, Novartis, and Roche; is on the advisory boards of Amgen, Celgene, Gilead, Janssen, Novartis, Pfizer, and Seattle Genetics; and serves on the speaker’s bureau at Amgen, Celgene, Gilead, Janssen, and Pfizer. The remaining authors declare no competing financial interests.

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Winkelmann, M., Blumenberg, V., Rejeski, K. et al. Prognostic value of the International Metabolic Prognostic Index for lymphoma patients receiving chimeric antigen receptor T-cell therapy. Eur J Nucl Med Mol Imaging 50, 1406–1413 (2023). https://doi.org/10.1007/s00259-022-06075-2

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