Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Immunotherapy

Safety and feasibility of chimeric antigen receptor T cell therapy after allogeneic hematopoietic cell transplantation in relapsed/ refractory B cell non-Hodgkin lymphoma

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1

References

  1. 1.

    Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377:2531–44.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    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.

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, et al. ASBMT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant. 2019;4:625–38.

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Brudno JN, Somerville RP, Shi V, Rose JJ, Halverson DC, Fowler DH, et al. Allogeneic T cells that express an anti-CD19 chimeric antigen receptor induce remissions of B-cell malignancies that progress after allogeneic hematopoietic stem-cell transplantation without causing graft-versus-host disease. J Clin Oncol. 2016;34:1112–21.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Kebriaei P, Singh H, Huls MH, Figliola MJ, Bassett R, Olivares S, et al. Phase I trials using sleeping beauty to generate CD19-specific CAR T cells. J Clin Invest. 2016;126:3363–76.

    Article  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Cruz CR, Micklethwaite KP, Savoldo B, Ramos CA, Lam S, Ku S, et al. Infusion of donor-derived CD19-redirected virus-specific T cells for B-cell malignancies relapsed after allogeneic stem cell transplant: a phase 1 study. Blood. 2013;122:2965–73.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Hirayama AV, Gauthier J, Hay KA, Voutsinas JM, Wu Q, Gooley T, et al. The response to lymphodepletion impacts PFS in aggressive non-Hodgkin lymphoma patients treated with CD19 CAR-T cells. Blood. 2019;133:1876–87.

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Ghosh A, Smith M, James SE, Davila ML, Velardi E, Argyropoulos KV, et al. Donor CD19 CAR T cells exert potent graft-versus-lymphoma activity with diminished graft-versus-host activity. Nat Med. 2017;23:242–9.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Jacoby E, Yang Y, Qin H, Chien CD, Kochenderfer JN, Fry TJ. Murine allogeneic CD19 CAR T cells harbor potent antileukemic activity but have the potential to mediate lethal GVHD. Blood. 2016;127:1361–70.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Lee DW, Kochenderfer JN, Stetler-Stevenson M, Cui YK, Delbrook C, Feldman SA, et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet. 2015;385:517–28.

    CAS  Article  Google Scholar 

  11. 11.

    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.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Park JH, Riviere I, Gonen M, Wang X, Senechal B, Curran KJ, et al. Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia. N Engl J Med. 2018;378:449–59.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Wilson WH, Young RM, Schmitz R, Yang Y, Pittaluga S, Wright G, et al. Targeting B cell receptor signaling with ibrutinib in diffuse large B cell lymphoma. Nat Med. 2015;21:922–6.

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Fraietta JA, Beckwith KA, Patel PR, Ruella M, Zheng Z, Barrett DM, et al. Ibrutinib enhances chimeric antigen receptor T-cell engraftment and efficacy in leukemia. Blood. 2016;127:1117–27.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. 15.

    Ruella M, Kenderian SS, Shestova O, Fraietta JA, Qayyum S, Zhang Q, et al. The addition of the BTK inhibitor ibrutinib to anti-CD19 chimeric antigen receptor T cells (CART19) improves responses against Mantle cell lymphoma. Clin Cancer Res. 2016;22:2684–96.

    CAS  Article  PubMed  Google Scholar 

Download references

Funding

This research was supported in part by NIH/NCI Cancer Center Support Grant P30 CA008748. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Miguel-Angel Perales.

Ethics declarations

Conflict of interest

CS—Consultant on advisory boards for: Juno Therapeutics, Sanofi-Genzyme, Spectrum Pharmaceuticals, Novartis, Precision Biosciences, Kite, a Gilead Company and GSK. Research funds for investigator-initiated trials from: Juno Therapeutics and Sanofi-Genzyme. GS—Research funding from Janssen and Amgen. MS—Consultancy: Angiocrine Bioscience, Inc., McKinsey & Company. Scott Avecilla—Honoraria for presenting a project in partnership with Abbott Laboratories. CB—Research funding from Epizyme, Novartis, Janssen, BMS, Miragen, Mediimmune; Consultancy from Defined Health, GLG, Guidepoint Global; Honoraria from Dava Oncology. MLP—Advisory Board for Celgene, Consultant for Merck and Pharmacyclics. SG—Advisory Board for Amgen, Actinuum, Celgene, Johnson & Johnson, Jazz pharmaceutical, Takeda, Novartis, Kite, Spectrum Pharma; Research funding from Amgen, Actinuum, Celgene, Johnson & Johnson, Miltenyi, Takeda, Miguel-Angel Perales - Honoraria from Abbvie, Bellicum, Bristol-Myers Squibb, Incyte, Merck, Novartis, Nektar Therapeutics, and Takeda. He serves on DSMBs for Servier and Medigene, and the scientific advisory boards of MolMed and NexImmune. Research support for clinical trials from Incyte, Kite (Gilead) and Miltenyi Biotec.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Jain, T., Sauter, C.S., Shah, G.L. et al. Safety and feasibility of chimeric antigen receptor T cell therapy after allogeneic hematopoietic cell transplantation in relapsed/ refractory B cell non-Hodgkin lymphoma. Leukemia 33, 2540–2544 (2019). https://doi.org/10.1038/s41375-019-0476-y

Download citation

Further reading

Search

Quick links