Evidence of long-lasting anti-CD19 activity of engrafted CD19 chimeric antigen receptor–modified T cells in a phase I study targeting pediatrics with acute lymphoblastic leukemia

Futian Ma, Jin Yuan Ho*, Huan Du, Fan Xuan, Xiaoli Wu, Qinglong Wang, Lin Wang, Ying Liu, Min Ba, Yizhuo Wang, Jianmin Luo, Jianqiang Li

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

Ninety percent of relapse/refractory B-cell acute lymphatic leukemia (R/R B-ALL) patients can achieve complete remission (CR) after CD19-targeting chimeric antigen receptor T (CAR-T) cell therapy. However, around 50% of them relapse in 1 year. Persistent CAR-T cell engraftment is considered as the key to remain durable remission. Here, we initiated a phase I study to treat 10 pediatric B-ALL patients using a CD19-targeted second generation CAR with a 4-1BB intracellular costimulatory domain. All patients received a standard fludarabine and cyclophosphamide (FC) preconditioning regiment, followed by a CAR-T infusion with a median number of 0.5 (0.3-1.58) × 106 CAR+ T cells/kg. The pretreatment tumor burdens were high with a median bone marrow (BM) blasts percentage of 59.2% (7.31%-86.2%), excluding one patient only with brain infiltration of leukemia cells (0% BM blasts). The initial CR rate was 80% (n = 8/10). Four patients (40%) experienced serious (grade > 2) cytokine release syndrome (CRS) and three patients (30%) with obvious neurotoxicity. Monthly assessments of CD19+ minimal residual disease (MRD) and CAR-T engraftment demonstrated the anti-CD19 activity of long-term engrafted CAR-T cell clones in one patient for more than 2 years.

Original languageEnglish
Pages (from-to)601-608
Number of pages8
JournalHematological Oncology
Volume37
Issue number5
DOIs
Publication statusPublished - 1 Dec 2019

Keywords

  • B-ALL
  • CAR-T
  • CD19
  • chimeric antigen receptor

Fingerprint

Dive into the research topics of 'Evidence of long-lasting anti-CD19 activity of engrafted CD19 chimeric antigen receptor–modified T cells in a phase I study targeting pediatrics with acute lymphoblastic leukemia'. Together they form a unique fingerprint.

Cite this