Cancer Res Treat.  2022 Jul;54(3):917-925. 10.4143/crt.2021.399.

Outcomes of Anti-CD19 CAR-T Treatment of Pediatric B-ALL with Bone Marrow and Extramedullary Relapse

• Wan X
• Yang X
• Yang F
• Wang T
• Ding L
• Song L
• Miao Y
• Wang X
• Ma Y
• Luo C
• Tang J
• Gu L
• Chen J
• Tang Y
• Lu J
• Li B

• KMID: 2531337
• DOI: http://doi.org/10.4143/crt.2021.399

Abstract

Purpose
Anti-CD19 chimeric antigen receptor T-cell immunotherapy (19CAR-T) has achieved impressive clinical results in adult and pediatric relapsed/refractory (r/r) B-lineage acute lymphoblastic leukemia (B-ALL). However, the application and effect of CAR-T therapy in B-ALL patients with extramedullary relapse are rarely issued even disqualified in some clinical trials. Here, we examined the efficacy of 19CAR-T in patients with both bone marrow and extramedullary involvement.
Materials and Methods
CAR-T cells were generated by transfection of primary human T lymphocytes with a lentiviral vector expressing anti-CD19 single chain antibody fragments (scFvs) with the cytoplasmic domains of 4-1BB and CD3ζ, and used to infuse patients diagnosed as having r/r B-ALL with extramedullary origination. Clinical responses were evaluated by the use of bone marrow aspiration, imaging, and flow cytometry.
Results
Eight patients received 19CAR-T infusion and all attained complete remission (CR). Only one patient was bridged to hematopoietic stem cell transplantation (HSCT). Although three patients relapsed after infusion, they received 19/22CAR-T infusion sequentially and attained a second remission. To date, five patients are in continuous CR and all eight patients are still alive. The mean follow-up time was 21.9 months, while the 24-month estimated event-free survival is 51.4%.
Conclusion
19CAR-T therapy can lead to clinical remission for extramedullary relapsed pediatric B-ALL patients. However, the problem of CD19+ relapses after CAR-T remained to be solved. For patients relapsing after CAR-T, a second CAR-T therapy creates another opportunity for remission for subsequent HSCT.

Keyword

B-ALL; Extramedullary relapse; CD19 CAR-T; Second CAR-T

Figure

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  Fig. 1 Clinical outcomes of 19CAR-T cells. (A) Swimmer plot (n=8), in which each bar represents an individual patient as designated. (B) Kaplan-Meier graph of event-free survival in eight patients infused with 19CAR-T cells, demonstrating 68.57% event-free survival at 12 months and 51.43% at 24 months. 19CAR-T, anti-CD19 chimeric antigen receptor T-cell; CAR-T, chimeric antigen receptor T-cell.

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  Fig. 2 Changes in patients’ serum biomarkers in cytokine release syndrome. (A) The temporal relationship of interleukin 6 (IL-6) (blue line) and interferon γ (IFN-γ) (red line) from day 0 to day 11. (B) The temporal relationship of IL-6 (blue line) and lymphocyte numbers (red line) from day 0 to day 8. (C) The number of copies of the chimeric antigen receptor (CAR) gene detected in Patient S005’s peripheral blood (PB) and cerebrospinal fluid(CSF). (D) The persistence of circulating chimeric antigen receptor T-cell (CAR-T) cells identified by quantitative polymerase chain reaction (qPCR). (E) B-cell aplasia remained in patient S003 but not in S001, who had been bridged to hematopoietic stem cell transplantation. (F) There were 90.7% leukemic cells in bone marrow from patient S003 detected on day 0 (left) but 0.0% on day 21 (right).

Reference

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