CD19-Specific CAR-T Cell Treatment of 115 Children and Young Adults with Acute B Lymphoblastic Leukemia: Long-term Follow-up

Cancer Res Treat. 2024 Jul;56(3):945-955. doi: 10.4143/crt.2023.1205. Epub 2024 Feb 13.

Abstract

Purpose: Chemotherapy has been the primary treatment for patients with B-cell acute lymphoblastic leukemia (B-ALL). However, there are still patients who are not sensitive to chemotherapy, including those with refractory/relapse (R/R) disease and those experiencing minimal residual disease (MRD) re-emergence. Chimeric antigen receptor-T lymphocytes (CAR-T) therapy may provide a new treatment option for these patients.

Materials and methods: Our institution conducted a single-arm prospective clinical trial (ChiCTR-OPN-17013507) using CAR-T-19 to treat R/R B-ALL and MRD re-emergent patients. One hundred and fifteen patients, aged 1-25 years (median age, 8 years), were enrolled, including 67 R/R and 48 MRD re-emergent CD19-positive B-ALL patients.

Results: All patients achieved morphologic complete remission (CR), and within 1 month after infusion, 111 out of 115 (96.5%) patients achieved MRD-negative CR. With a median follow-up time of 48.4 months, the estimated 4-year leukemia-free survival (LFS) rate and overall survival (OS) rate were 68.7%±4.5% and 70.7%±4.3%, respectively. There were no significant differences in long-term efficacy observed among patients with different disease statuses before infusion (4-year OS: MRD re-emergence vs. R/R B-ALL, 70.6%±6.6% vs. 66.5%±6.1%, p=0.755; 4-year LFS: MRD re-emergence vs. R/R B-ALL, 67.3%±7.0% vs. 63.8%±6.2%, p=0.704). R/R B-ALL patients bridging to transplantation after CAR-T treatment had a superior OS and LFS compared to those who did not. However, for MRD re-emergent patients, there was no significant difference in OS and LFS, regardless of whether they underwent hematopoietic stem cell transplantation or not.

Conclusion: CD19 CAR-T therapy effectively and safely cures both R/R B-ALL and MRD re-emergent patients.

Keywords: CD19 CAR-T therapy; MRD re-emergence; Prognosis; R/R B-ALL.

MeSH terms

  • Adolescent
  • Adult
  • Antigens, CD19* / immunology
  • Child
  • Child, Preschool
  • Female
  • Follow-Up Studies
  • Humans
  • Immunotherapy, Adoptive* / methods
  • Infant
  • Male
  • Neoplasm, Residual
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma* / immunology
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma* / mortality
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma* / therapy
  • Prospective Studies
  • Receptors, Chimeric Antigen / immunology
  • Treatment Outcome
  • Young Adult

Substances

  • Antigens, CD19
  • Receptors, Chimeric Antigen