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

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

• Wang Y
• Xue Yj
• Zuo Yx
• Jia Yp
• Lu Ad
• Zeng Hm
• Zhang Lp

• KMID: 2557681
• DOI: http://doi.org/10.4143/crt.2023.1205

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.

Keyword

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

Figure

• 

  Fig. 1. Consort diagram of patients based on disease status before infusion. B-ALL, B-cell acute lymphoblastic leukemia; BM, bone marrow; CCR, continuous complete remission; HSCT, hematopoietic stem cell transplantation; MRD, minimal residual disease; R/R, refractory/relapse.

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  Fig. 2. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) after CD19 chimeric antigen receptor (CAR) T-cell infusion. (A) The incidence of CRS and ICANS. (B) Subgroup analysis of severe CRS. (C, D) Peak interleukin 6 (IL-6) values and CAR T-cell expansion stratified by CRS grade 0-2 versus CRS grade 3-4. CI, confidence interval; EMD, extramedullary disease; HR, hazard ratio; HSCT, hematopoietic stem cell transplantation; MRD, minimal residual disease.

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  Fig. 3. Kaplan-Meier estimates of 4-year outcomes in the hematopoietic stem cell transplantation (HSCT) and non-HSCT arms in minimal residual disease (MRD) re-emergence and refractory/relapse B-cell acute lymphoblastic leukemia (R/R B-ALL). (A) Overall survival in MRD re-emergence group. (B) Leukemia-free survival in MRD re-emergence group. (C) Overall survival in R/R B-ALL group. (D) Leukemia-free survival in R/R B-ALL group.

Reference

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