The Molecular Mechanisms of CD19-Negative Relapse in B-Cell Lymphoma after CAR T-Cell Immunotherapy

The antigen receptor T cell (CAR T-cell) immunotherapy is the most antitumor ability in relapse/refractory (R/R) hematological malignancies but it still shows a high relapse rate. A few studies have been found that the molecular mechanisms of CD19-negative relapse after CAR T-cell therapy are the CD19 loss or down-regulation in lymphoma, including lineage switching, CD19 gene mutation, selective shearing, and subcloning of CD19-negative cell. The gene rearrangement, fusion genes and IL-6 may be to influent the therapeutic effect of CAR T-cell immunotherapy. The gene mutations of APX5, IKAROS, EBF1, GNA13, SOCS1, TNFALP3, XPO1, FLT3 etc. have been currently found after CAR T-cell therapy relapse. The review reports the molecular mechanisms of CD19-negative relapse in B-cell lymphoma after CAR T-cell immunotherapy.