CAR T-cells for acute leukemias in children: current status, challenges, and future directions

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 Lond. Engl., 385(9967), 517–528.

Article  Google Scholar 

Shah, N. N., Lee, D. W., Yates, B., et al. (2021). Long-term follow-up of CD19-CAR T-cell therapy in children and young adults with B-ALL. Journal of Clinical Oncology, 39(15), 1650–1659. https://doi.org/10.1200/JCO.20.02262

Article  PubMed  PubMed Central  Google Scholar 

Gardner, R. A., Finney, O., Annesley, C., et al. (2017). Intent-to-treat leukemia remission by CD19 CAR T cells of defined formulation and dose in children and young adults. Blood, 129(25), 3322–3331.

Article  PubMed  PubMed Central  Google Scholar 

Imai, C., Mihara, K., Andreansky, M., et al. (2004). Chimeric receptors with 4–1BB signaling capacity provoke potent cytotoxicity against acute lymphoblastic leukemia. Leukemia, 18(4), 676–684.

Article  PubMed  Google Scholar 

Maude, S. L., Frey, N., Shaw, P. A., et al. (2014). Chimeric antigen receptor T cells for sustained remissions in leukemia. New England Journal of Medicine, 371(16), 1507–1517.

Article  PubMed  Google Scholar 

Maude, S. L., Laetsch, T. W., Buechner, J., et al. (2018). Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. New England Journal of Medicine, 378(5), 439–448.

Article  PubMed  Google Scholar 

Laetsch, T. W., Maude, S. L., Rives, S., et al. (2022). Three-year update of tisagenlecleucel in pediatric and young adult patients with relapsed/refractory acute lymphoblastic leukemia in the ELIANA Trial. Journal Clinical Oncology, 41(9), 1664–1669. https://doi.org/10.1200/JCO.22.00642

Article  Google Scholar 

Curran, K. J., Margossian, S. P., Kernan, N. A., et al. (2019). Toxicity and response after CD19-specific CAR T-cell therapy in pediatric/young adult relapsed/refractory B-ALL. Blood, 134(26), 2361–2368.

Article  PubMed  PubMed Central  Google Scholar 

Ghorashian, S., Kramer, A. M., Onuoha, S., et al. (2019). Enhanced CAR T cell expansion and prolonged persistence in pediatric patients with ALL treated with a low-affinity CD19 CAR. Nature Medicine, 25(9), 1408–1414.

Article  PubMed  Google Scholar 

Wayne, A. S., Huynh, V., Hijiya, N., et al. (2023). Three-year results from phase I of ZUMA-4: KTE-X19 in pediatric relapsed/refractory acute lymphoblastic leukemia. Haematologica, 108(3), 747–760.

Article  PubMed  Google Scholar 

Myers, R. M., Jacoby, E., Pulsipher, M. A., et al. (2023). Clinical variables associated with improved outcomes for children and young adults treated with CAR T cells for B-ALL: A decade of CAR translation. Transplant Cell Theraphy, S2666–6367(23), 01420–01423.

Google Scholar 

Myers, R. M., Taraseviciute, A., Steinberg, S. M., et al. (2021). Blinatumomab nonresponse and high-disease burden are associated with inferior outcomes after CD19-CAR for B-ALL. Journal Clinical Oncology, 40(9), 932–944. https://doi.org/10.1200/JCO.21.01405

Article  Google Scholar 

Schultz, L. M., Baggott, C., Prabhu, S., et al. (2020). Disease burden impacts outcomes in pediatric and young adult B-cell acute lymphoblastic leukemia after commercial tisagenlecleucel: Results from the Pediatric Real World CAR Consortium (PRWCC). Blood, 136(Supplement 1), 14–15.

Article  Google Scholar 

Grupp, S., Hu, Z.-H., Zhang, Y., et al. (2019). Tisagenlecleucel chimeric antigen receptor (CAR) T-cell therapy for relapsed/refractory children and young adults with acute lymphoblastic leukemia (ALL): Real world experience from the Center for International Blood and Marrow Transplant Research (CIBMTR) and Cellular Therapy (CT) Registry. Blood, 134(Supplement_1), 2619–2619.

Article  Google Scholar 

Dourthe, M.-E., Rabian, F., Yakouben, K., et al. (2021). Determinants of CD19-positive vs CD19-negative relapse after tisagenlecleucel for B-cell acute lymphoblastic leukemia. Leukemia, 35(12), 3383–3393.

Article  PubMed  Google Scholar 

Ghorashian, S., Jacoby, E., De Moerloose, B., et al. (2022). Tisagenlecleucel therapy for relapsed or refractory B-cell acute lymphoblastic leukaemia in infants and children younger than 3 years of age at screening: An international, multicentre, retrospective cohort study. Lancet Haematol., 9(10), e766–e775.

Article  PubMed  Google Scholar 

Zhang, X., Yang, J., Li, J., et al. (2022). Factors associated with treatment response to CD19 CAR-T therapy among a large cohort of B cell acute lymphoblastic leukemia. Cancer Immunology Immunotherapy CII, 71(3), 689–703.

Article  PubMed  Google Scholar 

Leahy, A. B., Devine, K. J., Li, Y., et al. (2021). Impact of high-risk cytogenetics on outcomes for children and young adults receiving CD19-directed CAR T-cell therapy. Blood, 139(14), 2173–2185. https://doi.org/10.1182/blood.2021012727

Article  Google Scholar 

Bader, P., Rossig, C., Hutter, M., et al. (2023). CD19 CAR T cells are an effective therapy forposttransplant relapse in patients with B-lineage ALL: real-world data from Germany. Blood Advances, 7(11), 2436–2448. https://doi.org/10.1182/bloodadvances.2022008981

Article  PubMed  PubMed Central  Google Scholar 

Pillai, V., Muralidharan, K., Meng, W., et al. (2019). CAR T-cell therapy is effective for CD19-dim B-lymphoblastic leukemia but is impacted by prior blinatumomab therapy. Blood Advances, 3(22), 3539–3549.

Article  PubMed  PubMed Central  Google Scholar 

Mullanfiroze, K., Ottaviano, G., Mishra, A. K., et al. (2021). Outcomes of children and young adults with acute lymphoblastic leukaemia administered inotuzumab Pre CAR-T therapy. Blood, 138, 1743.

Article  Google Scholar 

Ceolin, V., Brivio, E., van Tinteren, H., et al. (2022). Outcome of chimeric antigen receptor T-cell therapy following treatment with inotuzumab ozogamicin in children with relapsed or refractory acute lymphoblastic leukemia. Leukemia, 37(1), 53–60. https://doi.org/10.1038/s41375-022-01740-9

Article  PubMed  Google Scholar 

Shahid, S., Ramaswamy, K., Flynn, J., et al. (2022). Impact of bridging chemotherapy on clinical outcoMES of CD19-specific CAR T cell therapy in children/young adults with relapsed/refractory B cell acute lymphoblastic leukemia. Transplant and Cellular Theraphy, 28(2), 72.e1-72.e8.

Article  Google Scholar 

Lecornec, N., Dourthe, M.-E., Rabian, F., et al. (2023). Low disease burden pre-CAR-T cell therapy for children and AYA with B-ALL is associated with an impaired outcome when obtained through intensification of the bridging therapy. Blood, 142, 2134.

Article  Google Scholar 

Myers, R. M., Li, Y., Barz Leahy, A., et al. (2021). Humanized CD19-Targeted Chimeric Antigen Receptor (CAR) T Cells in CAR-Naive and CAR-Exposed Children and Young Adults With Relapsed or Refractory Acute Lymphoblastic Leukemia. Journal of Clinical Oncology, 39(27), 3044–3055. https://doi.org/10.1200/JCO.20.03458

Article  PubMed  PubMed Central  Google Scholar 

Ravich, J. W., Huang, S., Zhoum, Y., et al. (2021). Impact of High Disease Burden on Survival in Pediatric Patients with B-ALL Treated with Tisagenlecleucel. Transplant Cellular Theraphy, 28(2), 73.e1-73.e9. https://doi.org/10.1016/j.jtct.2021.11.019

Article  Google Scholar 

Leahy, A. B., Newman, H., Li, Y., et al. (2021). 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., 8(10), e711–e722.

Article  PubMed  PubMed Central  Google Scholar 

Ortíz-Maldonado, V., Rives, S., Castellà, M., et al. (2021). CART19-BE-01: A multicenter trial of ARI-0001 cell therapy in patients with CD19+ relapsed/refractory malignancies. Molecular Theraphy Journal of the American Society of Gene Theraphy, 29(2), 636–644.

Article  Google Scholar 

Jacoby, E., Ghorashian, S., Vormoor, B., et al. (2022). CD19 CAR T-cells for pediatric relapsed acute lymphoblastic leukemia with active CNS involvement: A retrospective international study. Leukemia, 36(6), 1525–1532.

Article  PubMed  Google Scholar 

Fabrizio, V. A., Phillips, C. L., Lane, A., et al. (2022). Tisagenlecleucel outcomes in relapsed/refractory extramedullary ALL: A Pediatric Real World CAR Consortium Report. Blood Advances, 6(2), 600–610.

Article  PubMed  PubMed Central  Google Scholar 

Pulsipher, M. A., Han, X., Quigley, M., et al. (2018). Molecular detection of minimal residual disease precedes morphological relapse and could be used to identify relapse in pediatric and young adult B-cell acute lymphoblastic leukemia patients treated with tisagenlecleucel. Blood, 132(Supplement 1), 1551–1551.

Article  Google Scholar 

Myers, R. M., Shah, N. N., & Pulsipher, M. A. (2022). How I use risk factors for success or failure of CD19 CAR T cells to guide management of children and AYA with B-cell ALL. Blood, 141(11), 1251–1264. https://doi.org/10.1182/blood.2022016937

Article  PubMed Central  Google Scholar 

Lamble, A. J., Moskop, A., Pulsipher, M. A., et al. (2023). INSPIRED symposium part 2: Prevention and management of relapse following chimeric antigen receptor T Cell therapy for B cell acute lymphoblastic leukemiA. Transplant. Cell. Ther., 29(11), 674–684.

Article  PubMed  Google Scholar 

Singh, N. (2024). Analysis of pre-treatment tumors reveals gatekeepers of response to CAR T cells. Molecular Theraphy Journal of American Society Gene Theraphy, 32(3), 567–568.

Article 

Comments (0)

No login
gif