CD19 CAR T-cell therapy followed by emergence of a CD19-negative plasmablastic-like neoplasm in B-ALL: a case report

Chimeric antigen receptor (CAR) T cells targeting CD19 have transformed the treatment of relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). However, relapse following CAR T-cell therapy remains a major clinical challenge and may be associated with antigen loss or phenotypic evolution. Here, we report a patient with B-ALL treated with brexucabtagene autoleucel who achieved an initial complete remission, followed by rapid clinical deterioration characterized by malignant pleural and peritoneal effusions. Immunophenotypic analysis of the effusion revealed a CD19-negative, plasmablastic-like B-cell neoplasm developing in the presence of detectable CD19-targeting CAR T cells in peripheral blood, bone marrow, and serous cavities. Due to the observational nature of this single case and the absence of longitudinal molecular analyses, clonal transformation, lineage plasticity, and outgrowth of a pre-existing CD19-negative population cannot be distinguished. This report highlights diagnostic and therapeutic challenges associated with antigen-negative relapse after CAR T-cell therapy and underscores the importance of cautious interpretation of mechanisms in rare post-treatment disease phenotypes.