Skip to main content

Advertisement

Log in

Acute life-threatening toxicity from CAR T-cell therapy

  • What's New in Intensive Care
  • Published:
Intensive Care Medicine Aims and scope Submit manuscript

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

References

  1. Makita S, Yoshimura K, Tobinai K (2017) Clinical development of anti-CD19 chimeric antigen receptor T-cell therapy for B-cell non-Hodgkin lymphoma. Cancer Sci 108:1109–1118. https://doi.org/10.1111/cas.13239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Neelapu SS, Tummala S, Kebriaei P et al (2018) Chimeric antigen receptor T-cell therapy—assessment and management of toxicities. Nat Rev Clin Oncol 15:47–62. https://doi.org/10.1038/nrclinonc.2017.148

    Article  CAS  PubMed  Google Scholar 

  3. Weber JS, Yang JC, Atkins MB, Disis ML (2015) Toxicities of immunotherapy for the practitioner. J Clin Oncol Off J Am Soc Clin Oncol 33:2092–2099. https://doi.org/10.1200/JCO.2014.60.0379

    Article  CAS  Google Scholar 

  4. Assoun S, Lemiale V, Azoulay E (2019) Molecular targeted therapy-related life-threatening toxicity in patients with malignancies. A systematic review of published cases. Intensive Care Med 45:988–997. https://doi.org/10.1007/s00134-019-05650-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Neelapu SS, Locke FL, Bartlett NL et al (2017) Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med 377:2531–2544. https://doi.org/10.1056/NEJMoa1707447

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Maude SL, Laetsch TW, Buechner J et al (2018) Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med 378:439–448. https://doi.org/10.1056/NEJMoa1709866

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Schuster SJ, Svoboda J, Chong EA et al (2017) Chimeric antigen receptor T cells in refractory B-cell lymphomas. N Engl J Med 377:2545–2554. https://doi.org/10.1056/NEJMoa1708566

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Zhou H, Luo Y, Zhu S et al (2018) The efficacy and safety of anti-CD19/CD20 chimeric antigen receptor—T cells immunotherapy in relapsed or refractory B-cell malignancies:a meta-analysis. BMC Cancer 18:929. https://doi.org/10.1186/s12885-018-4817-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Hill JA, Li D, Hay KA et al (2018) Infectious complications of CD19-targeted chimeric antigen receptor-modified T-cell immunotherapy. Blood 131:121–130. https://doi.org/10.1182/blood-2017-07-793760

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Park JH, Romero FA, Taur Y et al (2018) Cytokine release syndrome grade as a predictive marker for infections in patients with relapsed or refractory B-cell acute lymphoblastic leukemia treated with chimeric antigen receptor T cells. Clin Infect Dis Off Publ Infect Dis Soc Am 67:533–540. https://doi.org/10.1093/cid/ciy152

    Article  CAS  Google Scholar 

  11. Lee DW, Santomasso BD, Locke FL et al (2019) ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Trans J Am Soc Blood Marrow Trans 25:625–638. https://doi.org/10.1016/j.bbmt.2018.12.758

    Article  CAS  Google Scholar 

  12. Frey N, Porter D (2019) Cytokine release syndrome with chimeric antigen receptor T cell therapy. Biol Blood Marrow Trans J Am Soc Blood Marrow Trans 25:e123–e127. https://doi.org/10.1016/j.bbmt.2018.12.756

    Article  CAS  Google Scholar 

  13. Jin Z, Xiang R, Qing K et al (2018) The severe cytokine release syndrome in phase I trials of CD19-CAR-T cell therapy: a systematic review. Ann Hematol 97:1327–1335. https://doi.org/10.1007/s00277-018-3368-8

    Article  CAS  PubMed  Google Scholar 

  14. Santomasso BD, Park JH, Salloum D et al (2018) Clinical and biological correlates of neurotoxicity associated with CAR T-cell therapy in patients with B-cell acute lymphoblastic leukemia. Cancer Discov 8:958–971. https://doi.org/10.1158/2159-8290.CD-17-1319

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Gust J, Taraseviciute A, Turtle CJ (2018) Neurotoxicity associated with CD19-targeted CAR-T cell therapies. CNS Drugs 32:1091–1101. https://doi.org/10.1007/s40263-018-0582-9

    Article  PubMed  PubMed Central  Google Scholar 

  16. Taraseviciute A, Tkachev V, Ponce R et al (2018) Chimeric antigen receptor T cell-mediated neurotoxicity in nonhuman primates. Cancer Discov 8:750–763. https://doi.org/10.1158/2159-8290.CD-17-1368

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Norelli M, Camisa B, Barbiera G et al (2018) Monocyte-derived IL-1 and IL-6 are differentially required for cytokine-release syndrome and neurotoxicity due to CAR T cells. Nat Med 24:739–748. https://doi.org/10.1038/s41591-018-0036-4

    Article  CAS  PubMed  Google Scholar 

  18. Giavridis T, van der Stegen SJC, Eyquem J et al (2018) CAR T cell-induced cytokine release syndrome is mediated by macrophages and abated by IL-1 blockade. Nat Med 24:731–738. https://doi.org/10.1038/s41591-018-0041-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ying Z, Huang XF, Xiang X et al (2019) A safe and potent anti-CD19 CAR T cell therapy. Nat Med 25:947–953. https://doi.org/10.1038/s41591-019-0421-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Sterner RM, Sakemura R, Cox MJ et al (2019) GM-CSF inhibition reduces cytokine release syndrome and neuroinflammation but enhances CAR-T cell function in xenografts. Blood 133:697–709. https://doi.org/10.1182/blood-2018-10-881722

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Elie Azoulay.

Ethics declarations

Conflicts of interest

Over the last 3 years, EA received honoraria or travel expense reimbursements from Alexion, Baxter, MSD, Ablynx, Pfizer, and Gilead. His hospital received research support from Gilead, Fisher & Payckle, Jazz Pharma, Ablynx, Baxter, Alexion, and Astellas. MD received consulting fees from Sanofi and Gilead-Kite, research support from Astute Medical and MSD, and speaker fees from MSD, Gilead-Kite and Astellas. SV received honoraria from Sanofi (teachings) and Pfizer (invitation to congress).

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Azoulay, E., Darmon, M. & Valade, S. Acute life-threatening toxicity from CAR T-cell therapy. Intensive Care Med 46, 1723–1726 (2020). https://doi.org/10.1007/s00134-020-06193-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00134-020-06193-1

Navigation