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Efficacy and safety of relmacabtagene autoleucel, an anti-CD19 chimeric antigen receptor T cell, in relapsed/refractory B-cell non-Hodgkin’s lymphoma: 2-year results of a phase 1 trial

Bone Marrow Transplantation volume 58, pages 288–294 (2023)Cite this article

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Abstract

This study reported 2-year efficacy and safety of relma-cel in Chinese patients with relapsed/refractory (R/R) B-cell non-Hodgkin’s lymphoma (B-NHL). In this phase 1 dose-escalating trial, patients received lymphodepleting chemotherapy for 3 days, followed by relma-cel as a single infusion in escalating dose levels (25 × 106, 50 × 106, 100 × 106, and 150 × 106 CAR-T cells). The endpoints included best objective response rate (ORR), best complete response rate (CRR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. A total of 23 patients were enrolled, including 60.9% with diffuse large B-cell lymphoma and 26.1% with follicular lymphoma. Twenty patients were evaluable for efficacy, and the best ORR was 85.0% and the best CRR was 75.0%. With a median follow-up of 24.2 months, 6 patients died and 2 had progressive disease, the median DOR, PFS, and OS were all not reached. The 2-year PFS and OS rates were 60.0% and 70.0%, respectively. Any grade and grade ≥ 2 cytokine release syndrome occurred in 18.2% and 13.6% of patients, respectively. Only 1(4.5%) patient had grade 3 CRS lasting 13 days, which was resolved by tocilizumab. No grade ≥ 2 neurotoxicity events or treatment-related deaths occurred. Patients with R/R B-NHL treated with relma-cel achieved durable response with favorable safety profile.

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Fig. 1: Flowchart.
Fig. 2: Tumor response.
Fig. 3: Survival curve.

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Data availability

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

References

  1. Al-Hamadani M, Habermann TM, Cerhan JR, Macon WR, Maurer MJ, Go RS. Non-Hodgkin lymphoma subtype distribution, geodemographic patterns, and survival in the US: A longitudinal analysis of the National Cancer Data Base from 1998 to 2011. Am J Hematol. 2015;90:790–5. https://doi.org/10.1002/ajh.24086.

    Article  PubMed  Google Scholar 

  2. Sehn LH, Berry B, Chhanabhai M, Fitzgerald C, Gill K, Hoskins P. et al. The revised International Prognostic Index (R-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP. Blood. 2007;109:1857–61. https://doi.org/10.1182/blood-2006-08-038257.

    Article  CAS  PubMed  Google Scholar 

  3. 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 

  4. Miller KD, Nogueira L, Mariotto AB, Rowland JH, Yabroff KR, Alfano CM, et al. Cancer treatment and survivorship statistics, 2019. CA Cancer J Clin. 2019;69:363–85. https://doi.org/10.3322/caac.21565.

    Article  PubMed  Google Scholar 

  5. Crump M, Neelapu SS, Farooq U, Van Den Neste E, Kuruvilla J, Westin J, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017;130:1800–8. https://doi.org/10.1182/blood-2017-03-769620.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Casulo C, Barr PM. How I treat early-relapsing follicular lymphoma. Blood. 2019;133:1540–7. https://doi.org/10.1182/blood-2018-08-822148.

    Article  CAS  PubMed  Google Scholar 

  7. Batlevi CL, Sha F, Alperovich A, Ni A, Smith K, Ying Z. et al. Follicular lymphoma in the modern era: survival, treatment outcomes, and identification of high-risk subgroups. Blood Cancer J. 2020;10:74. https://doi.org/10.1038/s41408-020-00340-z.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Abramson JS. Anti-CD19 CAR T-cell therapy for B-cell non-hodgkin lymphoma. Transfus Med Rev. 2020;34:29–33. https://doi.org/10.1016/j.tmrv.2019.08.003.

    Article  PubMed  Google Scholar 

  9. Ying Z, Song Y, Zhu J. Effectiveness and safety of Anti-CD19 Chimeric antigen receptor-T cell immunotherapy in patients with relapsed/refractory large B-cell lymphoma: a systematic review and meta-analysis. Front Pharm. 2022;13:834113 https://doi.org/10.3389/fphar.2022.834113.

    Article  CAS  Google Scholar 

  10. Ying Z, Yang H, Guo Y, Li W, Zou D, Zhou D. et al. Relmacabtagene autoleucel (relma-cel) CD19 CAR-T therapy for adults with heavily pretreated relapsed/refractory large B-cell lymphoma in China. Cancer Med. 2021;10:999–1011. https://doi.org/10.1002/cam4.3686.

    Article  CAS  PubMed  Google Scholar 

  11. Wang W, Hao M, Cheng Y, Gao J, Yang S, Liu Y, et al. JWCAR029 Is a CD19-Targeted CAR T cell product with process and quality controls delivered as a flat dose of CAR T cell to patients with NHL. Blood. 2018;132:5387–5387. https://doi.org/10.1182/blood-2018-99-114434.

    Article  Google Scholar 

  12. Ying Z, Xu P, Wang L, Cheng S, Wu W, Wang W, et al. Clinical response in Relapsed/Refractory (R/R) B-NHL treated with the CD19-Directed CAR T-cell product JWCAR029. Blood. 2019;134:2876 https://doi.org/10.1182/blood-2019-127751.

    Article  Google Scholar 

  13. Yan Z-X, Li L, Wang W, OuYang B-S, Cheng S, Wang L. et al. Clinical efficacy and tumor microenvironment influence in a dose-escalation study of Anti-CD19 chimeric antigen receptor T cells in refractory B-cell non-hodgkin’s lymphoma. Clin Cancer Res. 2019;25:6995–7003. https://doi.org/10.1158/1078-0432.CCR-19-0101.

    Article  CAS  PubMed  Google Scholar 

  14. Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E. 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 

  15. Li DH, Whitmore JB, Guo W, Ji Y. Toxicity and efficacy probability interval design for phase I adoptive cell therapy dose-finding clinical trials. Clin Cancer Res. 2017;23:13–20. https://doi.org/10.1158/1078-0432.CCR-16-1125.

    Article  CAS  PubMed  Google Scholar 

  16. Locke FL, Ghobadi A, Jacobson CA, Miklos DB, Lekakis LJ, Oluwole OO. et al. 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;20:31–42. https://doi.org/10.1016/s1470-2045(18)30864-7.

    Article  CAS  PubMed  Google Scholar 

  17. Schuster SJ, Tam CS, Borchmann P, Worel N, McGuirk JP, Holte H. et al. Long-term clinical outcomes of tisagenlecleucel in patients with relapsed or refractory aggressive B-cell lymphomas (JULIET): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2021;22:1403–15. https://doi.org/10.1016/s1470-2045(21)00375-2.

    Article  CAS  PubMed  Google Scholar 

  18. Abramson JS, Palomba ML, Gordon LI, Lunning MA, Wang M, Arnason J. et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet. 2020;396:839–52. https://doi.org/10.1016/s0140-6736(20)31366-0.

    Article  CAS  PubMed  Google Scholar 

  19. Gargett T, Truong N, Ebert LM, Yu W, Brown MP. Optimization of manufacturing conditions for chimeric antigen receptor T cells to favor cells with a central memory phenotype. Cytotherapy. 2019;21:593–602. https://doi.org/10.1016/j.jcyt.2019.03.003.

    Article  CAS  PubMed  Google Scholar 

  20. Ying Z, He T, Jin S, Wang X, Zheng W, Lin N. et al. A durable 4-1BB-based CD19 CAR-T cell for treatment of relapsed or refractory non-Hodgkin lymphoma. Chin J Cancer Res. 2022;34:53–62. https://doi.org/10.21147/j.issn.1000-9604.2022.01.05.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Cappell KM, Sherry RM, Yang JC, Goff SL, Vanasse DA, McIntyre L. et al. Long-term follow-up of anti-CD19 chimeric antigen receptor T-cell therapy. J Clin Oncol. 2020;38:3805–15. https://doi.org/10.1200/JCO.20.01467.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Hirayama AV, Gauthier J, Hay KA, Voutsinas JM, Wu Q, Pender BS. et al. High rate of durable complete remission in follicular lymphoma after CD19 CAR-T cell immunotherapy. Blood. 2019;134:636–40. https://doi.org/10.1182/blood.2019000905.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Schuster SJ, Svoboda J, Chong EA, Nasta SD, Mato AR, Anak O. 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 

  24. Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H. et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N. Engl J Med. 2018;378:439–48. https://doi.org/10.1056/NEJMoa1709866.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Bishop MR, Dickinson M, Purtill D, Barba P, Santoro A, Hamad N. et al. Second-line tisagenlecleucel or standard care in aggressive B-cell lymphoma. N. Engl J Med. 2022;386:629–39. https://doi.org/10.1056/NEJMoa2116596.

    Article  CAS  PubMed  Google Scholar 

  26. Itzhaki O, Jacoby E, Nissani A, Levi M, Nagler A, Kubi A. et al. Head-to-head comparison of in-house produced CD19 CAR-T cell in ALL and NHL patients. J Immunother Cancer. 2020;8:e000148. https://doi.org/10.1136/jitc-2019-000148.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP. 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 

  28. Sesques P, Ferrant E, Safar V, Wallet F, Tordo J, Dhomps A. et al. Commercial anti-CD19 CAR T cell therapy for patients with relapsed/refractory aggressive B cell lymphoma in a European center. Am J Hematol. 2020;95:1324–33. https://doi.org/10.1002/ajh.25951.

    Article  CAS  PubMed  Google Scholar 

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Funding

All funding is provided by JW Therapeutics (Shanghai) Co. Ltd.

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Authors and Affiliations

  1. Department of Lymphoma, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, 100142, China

    Zhitao Ying, Yan Xie, Wen Zheng, Weiping Liu, Ningjing Lin, Meifeng Tu, Xiaopei Wang, Lingyan Ping, Lijuan Deng, Chen Zhang, Meng Wu, Feier Feng, Tingting Du, Yongjing Tang, Yuqin Song & Jun Zhu

  2. JW Therapeutics (Shanghai) Co., Ltd, Shanghai, 201210, China

    Fang Su, Ziyu Guo & James Li

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Contributions

ZY: Patient enrollment, data acquisition, patient evaluation, and article preparation. YX, WZ, WL, NL, MT, XW, LP, LD, CZ, MW, FF, TD, YT: Patient enrollment and data acquisition. FS, ZG, JL: Project administration and supervision. YS: Data acquisition, statistical analysis, blood sample collection, patient evaluation, and article review. JZ: Project administration, patient enrollment, data acquisition, and article review.

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Correspondence to Yuqin Song or Jun Zhu.

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Ying, Z., Xie, Y., Zheng, W. et al. Efficacy and safety of relmacabtagene autoleucel, an anti-CD19 chimeric antigen receptor T cell, in relapsed/refractory B-cell non-Hodgkin’s lymphoma: 2-year results of a phase 1 trial. Bone Marrow Transplant 58, 288–294 (2023). https://doi.org/10.1038/s41409-022-01888-z

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