Journal of Clinical Pediatrics >
Efficacy and safety of CD19 targeted CAR-T cells in the treatment of refractory/relapsed B-cell acute lymphoblastic leukemia in children and adolescents
Received date: 2024-03-12
Online published: 2024-07-08
Objective To explore the efficacy and safety of CD19 chimeric antigen receptor T cells (CAR-T) in the treatment of refractory/relapsed B-cell acute lymphoblastic leukemia (B-ALL) in children and adolescents. Methods The clinical data of refractory/relapsed B-ALL patients<25 years old who received CD19 CAR-T therapy from June 2017 to March 2021 were retrospectively analyzed and the efficacy and safety of this therapy was evaluated. Results A total of 64 patients (35 boys and 29 girls) with refractory/relapsed B-ALL were included, and the median age was 8.5 (1.0-17.0) years old. One month following CD19 CAR-T infusion, a short-term effectiveness assessment of all 64 patients showed minimal residual disease (MRD) negative in 62 of them, and complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) in all 64 patients. The incidence rates of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were 78.1 % and 23.4 %, respectively. Twenty-two patients experienced recurrence after infusion, with a median recurrence time of 10.1 months. The 4-year overall survival (OS) rate was 66.0 %±6.0 %, and the 4-year leukemia free survival (LFS) rate was 63.0 %±6.0 %. Long-term follow-up results demonstrated superior LFS and OS in patients bridged to allogeneic hematopoietic stem cell transplantation (allo-HSCT) compared to those who were not bridged to transplantation (4-year LFS: 81.8 %±6.2 % vs. 24.0 %±9.8 %, 4-year OS: 81.4 %±5.9 % vs. 44.4 %±11.2 %; both P<0.01). Conclusions CD19 CAR-T therapy can effectively treat refractory/relapsed B-ALL, and bridging to HSCT after infusion can further improve the long-term survival outcomes in patients.
Yu WANG , Yujuan XUE , Yingxi ZUO , Yueping JIA , Aidong LU , Huimin ZENG , Leping ZHANG . Efficacy and safety of CD19 targeted CAR-T cells in the treatment of refractory/relapsed B-cell acute lymphoblastic leukemia in children and adolescents[J]. Journal of Clinical Pediatrics, 2024 , 42(7) : 583 -588 . DOI: 10.12372/jcp.2024.24e0207
| [1] | Cui L, Li ZG, Chai YH, et al. Outcome of children with newly diagnosed acute lymphoblastic leukemia treated with CCLG-ALL 2008: the first nation-wide prospective multicenter study in China[J]. Am J Hematol, 2018, 93(7): 913-920. |
| [2] | Yu CH, Jou ST, Su YH, et al. Clinical impact of minimal residual disease and genetic subtypes on the prognosis of childhood acute lymphoblastic leukemia[J]. Cancer, 2023, 129(5): 790-802. |
| [3] | Koh KN, Im HJ, Kim H, et al. Outcome of reinduction chemotherapy with a modified dose of idarubicin for children with marrow-relapsed acute lymphoblastic leukemia: results of the childhood acute lymphoblastic leukemia (CALL)-0603 study[J]. J Korean Med Sci, 2017, 32(4): 642-649. |
| [4] | Li Z, Yang K, Song Y, et al. CAR-T therapy followed by allogeneic hematopoietic stem cell transplantation for refractory/relapsed acute B lymphocytic leukemia: long-term follow-up results[J]. Front Oncol, 2023, 12: 1048296. |
| [5] | Park JH, Riviere I, Gonen M, et al. Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia[J]. N Engl J Med, 2018, 378(5): 449-459. |
| [6] | Zhang X, Yang J, Li J, et al. Factors associated with treatment response to CD19 CAR-T therapy among a large cohort of B cell acute lymphoblastic leukemia[J]. Cancer Immunol Immunother, 2022, 71(3): 689-703. |
| [7] | An F, Wang H, Liu Z, et al. Influence of patient characteristics on chimeric antigen receptor T cell therapy in B-cell acute lymphoblastic leukemia[J]. Nat Commun, 2020, 11(1): 5928. |
| [8] | Hay KA, Gauthier J, Hirayama AV, et al. Factors associated with durable EFS in adult B-cell ALL patients achieving MRD-negative CR after CD19 CAR T-cell therapy[J]. Blood, 2019, 133(15): 1652-1663. |
| [9] | Hunger SP, Mullighan CG. Acute lymphoblastic leukemia in children[J]. N Engl J Med, 2015, 373(16): 1541-1552. |
| [10] | Lee DW, Santomasso BD, Locke FL, et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells[J]. Biol Blood Marrow Transplant, 2019, 25(4): 625-638. |
| [11] | National Cancer Institute. Common terminology criteria for adverse events (CTCAE). Version 5.0[EB/OL]. 2018 [2024-03-12]. https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_8.5x11.pdf. |
| [12] | Zhang X, Lu XA, Yang J, et al. Efficacy and safety of anti-CD19 CAR T-cell therapy in 110 patients with B-cell acute lymphoblastic leukemia with high-risk features[J]. Blood Adv, 2020, 4(10): 2325-2338. |
| [13] | Shah NN, Lee DW, Yates B, et al. Long-term follow-up of CD19-CAR T-Cell therapy in children and young adults with B-ALL[J]. J Clin Oncol, 2021, 39(15): 1650-1659. |
| [14] | Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene ciloleucel CAR T-Cell therapy in refractory large B-cell lymphoma[J]. N Engl J Med, 2017, 377(26): 2531-2544. |
| [15] | Schuster SJ, Bishop MR, Tam CS, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma[J]. N Engl J Med, 2019, 380(1): 45-56. |
| [16] | Abramson JS, Palomba ML, Gordon LI, et al. Liso-cabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study[J]. Lancet, 2020, 396(10254): 839-852. |
| [17] | Molinos-Quintana á, Alonso-Saladrigues A, Herrero B, et al. Impact of disease burden and late loss of B cell aplasia on the risk of relapse after CD19 chimeric antigen receptor T Cell (Tisagenlecleucel) infusion in pediatric and young adult patients with relapse/refractory acute lymphoblastic leukemia: role of B-cell monitoring[J]. Front Immunol, 2024, 14: 1280580. |
| [18] | Eldfors S, Kuusanmaki H, Kontro M, et al. Idelalisib sensitivity and mechanisms of disease progression in relapsed TCF3-PBX1 acute lymphoblastic leukemia[J]. Leukemia, 2017, 31(1): 51-57. |
| [19] | Hu L, Charwudzi A, Li Q, et al. Anti-CD19 CAR-T cell therapy bridge to HSCT decreases the relapse rate and improves the long-term survival of R/R B-ALL patients: a systematic review and meta-analysis[J]. Ann Hematol, 2021, 100(4): 1003-1012. |
| [20] | Ruella M, Korell F, Porazzi P, et al. Mechanisms of resistance to chimeric antigen receptor-T cells in haematological malignancies[J]. Nat Rev Drug Discov, 2023, 22(12): 976-995. |
| [21] | Lee DW, Kochenderfer JN, Stetler-Stevenson M, et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial[J]. Lancet, 2015, 385(9967): 517-528. |
| [22] | Maude SL, Laetsch TW, Buechner J, et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia[J]. N Engl J Med, 2018, 378(5): 439-448. |
| [23] | Qi Y, Zhao M, Hu Y, et al. Efficacy and safety of CD19-specific CAR T cell-based therapy in B-cell acute lymphoblastic leukemia patients with CNSL[J]. Blood, 2022, 139(23): 3376-3386. |
/
| 〈 |
|
〉 |
