Early and Late Toxicities of Chimeric Antigen Receptor T-Cells

Overview

Journal Hematol Oncol Clin North Am

Specialties Hematology
Oncology

Date 2023 Jun 22

PMID 37349152

Authors

Rebecca Epperly

Victoria M Giordani

Lekha Mikkilineni

Nirali N Shah

Affiliations

Soon will be listed here.

Abstract

As chimeric antigen receptor (CAR) T-cell therapy is increasingly integrated into clinical practice across a range of malignancies, identifying and treating inflammatory toxicities will be vital to success. Early experiences with CD19-targeted CAR T-cell therapy identified cytokine release syndrome and neurotoxicity as key acute toxicities and led to unified initiatives to mitigate the influence of these complications. In this section, we provide an update on the current state of CAR T-cell-related toxicities, with an emphasis on emerging acute toxicities affecting additional organ systems and considerations for delayed toxicities and late effects.

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References

Dreyzin A, Jacobsohn D, Angiolillo A, Wistinghausen B, Schore R, Perez E . Intravenous anakinra for tisagenlecleucel-related toxicities in children and young adults. Pediatr Hematol Oncol. 2021; 39(4):370-378. DOI: 10.1080/08880018.2021.1988012. View

Brown B, Tambaro F, Kohorst M, Chi L, Mahadeo K, Tewari P . Immune Effector Cell Associated Neurotoxicity (ICANS) in Pediatric and Young Adult Patients Following Chimeric Antigen Receptor (CAR) T-Cell Therapy: Can We Optimize Early Diagnosis?. Front Oncol. 2021; 11:634445. PMC: 7982581. DOI: 10.3389/fonc.2021.634445. View

de Tena P, Bailen R, Oarbeascoa G, Gomez-Centurion I, Perez-Corral A, Carbonell D . Allogeneic CD34-selected stem cell boost as salvage treatment of life-threatening infection and severe cytopenias after CAR-T cell therapy. Transfusion. 2022; 62(10):2143-2147. DOI: 10.1111/trf.17071. View

Kritchevsky D, Klurfeld D . Influence of caloric intake on experimental carcinogenesis: a review. Adv Exp Med Biol. 1986; 206:55-68. DOI: 10.1007/978-1-4613-1835-4_7. View

Armenian S, Sun C, Kawashima T, Arora M, Leisenring W, Sklar C . Long-term health-related outcomes in survivors of childhood cancer treated with HSCT versus conventional therapy: a report from the Bone Marrow Transplant Survivor Study (BMTSS) and Childhood Cancer Survivor Study (CCSS). Blood. 2011; 118(5):1413-20. PMC: 3152502. DOI: 10.1182/blood-2011-01-331835. View

Drillet G, Lhomme F, de Guibert S, Manson G, Houot R . Prolonged thrombocytopenia after CAR T-cell therapy: the role of thrombopoietin receptor agonists. Blood Adv. 2022; 7(4):537-540. PMC: 9979763. DOI: 10.1182/bloodadvances.2022008066. View

Yan Z, Zhang H, Cao J, Zhang C, Liu H, Huang H . Characteristics and Risk Factors of Cytokine Release Syndrome in Chimeric Antigen Receptor T Cell Treatment. Front Immunol. 2021; 12:611366. PMC: 7940756. DOI: 10.3389/fimmu.2021.611366. View

Logue J, Zucchetti E, Bachmeier C, Krivenko G, Larson V, Ninh D . Immune reconstitution and associated infections following axicabtagene ciloleucel in relapsed or refractory large B-cell lymphoma. Haematologica. 2020; 106(4):978-986. PMC: 8017820. DOI: 10.3324/haematol.2019.238634. View

Baur K, Heim D, Beerlage A, Poerings A, Kopp B, Medinger M . Dasatinib for treatment of CAR T-cell therapy-related complications. J Immunother Cancer. 2022; 10(12). PMC: 9717332. DOI: 10.1136/jitc-2022-005956. View

10.

Roberts S, Dougan M . Checking ovarian reserves after checkpoint blockade. Nat Cancer. 2022; 3(8):907-908. DOI: 10.1038/s43018-022-00422-w. View

11.

Fried S, Avigdor A, Bielorai B, Meir A, Besser M, Schachter J . Early and late hematologic toxicity following CD19 CAR-T cells. Bone Marrow Transplant. 2019; 54(10):1643-1650. DOI: 10.1038/s41409-019-0487-3. View

12.

Dholaria B, Bachmeier C, Locke F . Mechanisms and Management of Chimeric Antigen Receptor T-Cell Therapy-Related Toxicities. BioDrugs. 2018; 33(1):45-60. PMC: 6733400. DOI: 10.1007/s40259-018-0324-z. View

13.

Korell F, Schubert M, Sauer T, Schmitt A, Derigs P, Weber T . Infection Complications after Lymphodepletion and Dosing of Chimeric Antigen Receptor T (CAR-T) Cell Therapy in Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia or B Cell Non-Hodgkin Lymphoma. Cancers (Basel). 2021; 13(7). PMC: 8038233. DOI: 10.3390/cancers13071684. View

14.

Martin-Rojas R, Gomez-Centurion I, Bailen R, Bastos M, Diaz-Crespo F, Carbonell D . Hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS) following treatment with tisagenlecleucel. Clin Case Rep. 2022; 10(1):e05209. PMC: 8741874. DOI: 10.1002/ccr3.5209. View

15.

Wang J, Doran J . The Many Faces of Cytokine Release Syndrome-Related Coagulopathy. Clin Hematol Int. 2021; 3(1):3-12. PMC: 8432322. DOI: 10.2991/chi.k.210117.001. View

16.

Winship A, Alesi L, Sant S, Stringer J, Cantavenera A, Hegarty T . Checkpoint inhibitor immunotherapy diminishes oocyte number and quality in mice. Nat Cancer. 2022; 3(8):1-13. DOI: 10.1038/s43018-022-00413-x. View

17.

Dhakal B, Abedin S, Fenske T, Chhabra S, Ledeboer N, Hari P . Response to SARS-CoV-2 vaccination in patients after hematopoietic cell transplantation and CAR T-cell therapy. Blood. 2021; 138(14):1278-1281. PMC: 8332674. DOI: 10.1182/blood.2021012769. View

18.

Maude S, Frey N, Shaw P, Aplenc R, Barrett D, Bunin N . Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014; 371(16):1507-17. PMC: 4267531. DOI: 10.1056/NEJMoa1407222. View

19.

Lee D, Kochenderfer J, Stetler-Stevenson M, Cui Y, Delbrook C, Feldman S . T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet. 2014; 385(9967):517-528. PMC: 7065359. DOI: 10.1016/S0140-6736(14)61403-3. View

20.

Leahy A, Newman H, Li Y, Liu H, Myers R, DiNofia A . CD19-targeted chimeric antigen receptor T-cell therapy for CNS relapsed or refractory acute lymphocytic leukaemia: a post-hoc analysis of pooled data from five clinical trials. Lancet Haematol. 2021; 8(10):e711-e722. PMC: 9026766. DOI: 10.1016/S2352-3026(21)00238-6. View