Hostname: page-component-cd9895bd7-p9bg8 Total loading time: 0 Render date: 2024-12-18T00:47:23.756Z Has data issue: false hasContentIssue false

Chimeric antigen receptor T-cell neuropsychiatric toxicity in acute lymphoblastic leukemia

Published online by Cambridge University Press:  04 January 2017

Vasthie Prudent*
Affiliation:
Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, New York, New York Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine Sylvester Cancer Center, Miami, Florida
William S. Breitbart
Affiliation:
Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, New York, New York
*
Address correspondence and reprint requests to: Vasthie Prudent, 1475 NW 12th Avenue, University of Miami Miller School of Medicine, Suite C021, Locator code D21, Miami, Florida 33136. E-mail: vasthieprudent.md@gmail.com.

Abstract

Chimeric antigen receptor T cells are used in the treatment of B-cell leukemias. Common chimeric antigen receptor T-cell toxicities can range from mild flu-like symptoms, such as fever and myalgia, to a more striking neuropsychiatric toxicity that can present as discrete neurological symptoms and delirium. We report here two cases of chimeric antigen receptor T-cell neuropsychiatric toxicity, one who presented as a mild delirium and aphasia that resolved without intervention, and one who presented with delirium, seizures, and respiratory insufficiency requiring intensive treatment. The current literature on the treatment and proposed mechanisms of this clinically challenging chimeric antigen receptor T-cell complication is also presented.

Type
Case Report
Copyright
Copyright © Cambridge University Press 2017 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Barrett, D.M., Teachey, D.T. & Grupp, S.A. (2014). Toxicity management for patients receiving novel T-cell engaging therapies. Current Opinion in Pediatrics, 26(1), 4349. Available from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4198063/pdf/nihms607686.pdf.Google Scholar
Cao, Y., Rodgers, D.T., Du, J., et al. (2016). Design of switchable chimeric antigen receptor T cells targeting breast cancer. Angewandte Chemie (International Ed. in English) , 55(26), 75207524. Epub ahead of print May 4.CrossRefGoogle ScholarPubMed
Deng, Z., Wu, Y., Ma, W., et al. (2015). Adoptive T-cell therapy of prostate cancer targeting the cancer stem cell antigen EpCAM. BMC Immunology, 16, 1. Available from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4318439/pdf/12865_2014_Article_64.pdf.Google Scholar
Davila, M.L., Riviere, I., Wang, X., et al. (2014). Efficacy and toxicity management of 19–28z CAR–T cell therapy in B cell acute lymphoblastic leukemia. Science Translational Medicine, 6(224), 224ra25. Available from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4684949/pdf/nihms744123.pdf.CrossRefGoogle ScholarPubMed
Drent, E., Groen, R.W., Noort, W.A., et al. (2016). Pre-clinical evaluation of CD38 chimeric antigen receptor engineered T cells for the treatment of multiple myeloma. Haematologica, 101(5), 616625. Epub ahead of print Feb 8. Available from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004365/pdf/1010616.pdf.Google Scholar
Fisher, D.T., Chen, Q., Skitzki, J.J., et al. (2011). IL-6 trans-signaling licenses mouse and human tumor microvascular gateways for trafficking of cytotoxic T cells. Journal of Clinical Investigation, 121(10), 38463859. Epub ahead of print Sep 19. Available from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3195455/pdf/JCI44952.pdf.Google Scholar
Giordano Attianese, G.M., Marin, V., Hoyos, V., et al. (2011). In vitro and in vivo model of a novel immunotherapy approach for chronic lymphocytic leukemia by anti-CD23 chimeric antigen receptor. Blood, 117(18), 4736–4645. Epub ahead of print Mar 15. Available from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3100686/.CrossRefGoogle ScholarPubMed
Gruol, D.L. (2015). IL-6 regulation of synaptic function in the CNS. Neuropharmacology, 96(Pt. A), 4254. Epub ahead of print Nov 22, 2014. Available from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4446251/pdf/nihms644784.pdf.Google Scholar
Lee, D.W., Gardner, R., Porter, D.L., et al. (2014). Current concepts in the diagnosis and management of cytokine release syndrome. Blood, 124(2), 188195. Epub ahead of print May 29. Available from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4093680/.Google Scholar
Lee, D.W., Kochenderfer, J.N., Stetler-Stevenson, M., et al. (2015). T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: A phase 1 dose-escalation trial. Lancet, 385(9967), 517528. Epub ahead of print Oct 13, 2014.Google Scholar
Maude, S.L., Frey, N., Shaw, P.A., et al. (2014 a). Chimeric antigen receptor T cells for sustained remissions in leukemia. The New England Journal of Medicine, 371(16), 15071517. Available from http://www.nejm.org/doi/pdf/10.1056/NEJMoa1407222.Google Scholar
Maude, S.L., Barrett, D., Teachey, D.T., et al. (2014 b). Managing cytokine release syndrome associated with novel T-cell-engaging therapies. Cancer Journal, 20(2), 119122. Available from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4119809/pdf/nihms607703.pdf.Google Scholar
Maus, M.V., Grupp, S.A., Porter, D.L., et al. (2014). Antibody-modified T cells: CARs take the front seat for hematologic malignancies. Blood, 123(17), 26252635. Epub ahead of print Feb 27. Available from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3999751/.CrossRefGoogle ScholarPubMed
Porter, D.L., Hwang, W.T., Frey, N.V., et al. (2015). Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Science Translational Medicine, 7(303), 303ra139.CrossRefGoogle ScholarPubMed
Ritchie, D.S., Neeson, P.J., Khot, A., et al. (2013). Persistence and efficacy of second generation CAR T cell against the LeY antigen in acute myeloid leukemia. Molecular Therapy, 21(11), 21222129. Epub ahead of print Jul 8. Available from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3831035/pdf/mt2013154a.pdf.Google Scholar
Tasian, S.K. & Gardner, R.A. (2015). CD19-redirected chimeric antigen receptor-modified T cells: A promising immunotherapy for children and adults with B-cell acute lymphoblastic leukemia (ALL). Therapeutic Advances in Hematology, 6(5), 228241. Available from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4556967/pdf/10.1177_2040620715588916.pdf.CrossRefGoogle ScholarPubMed