靶向 CD19 的 CAR-T 细胞疗法治疗多发性骨髓瘤的进展

INTRODUCTION: Emerging evidence suggests that, while CD19 is primarily expressed on immature B-cell precursors, it is also present on drug-resistant plasma cells that have been postulated to function as multiple myeloma (MM) stem cells, driving the progression of relapsing disease. Targeting CD19 with chimeric antigen receptor (CAR) T cells offers a promising strategy for addressing this residual disease burden, potentially leading to more durable treatments and enhanced relapse prevention. AREAS COVERED: This review examines the molecular basis of CD19-targeted CAR-T therapy in MM, highlighting its potential, key challenges, and efficacy and safety in early clinical trials for relapsed/refractory and newly diagnosed MM.

EXPERT OPINION: CD19 expression in MM correlates with poor prognosis and may be significantly underestimated, particularly following debulking therapy, as demonstrated by advanced visualization technologies like single molecule-sensitive direct stochastic optical reconstruction microscopy (dSTORM).

Early-phase trials using CD19-directed CAR-T as post-transplant consolidation show promise in prolonging progression-free survival. Multi-target approaches, e. g. the bispecific BCMA CD19 CAR-T product GC012F, are advancing through clinical development with encouraging safety and efficacy data.

However, randomized controlled trials will be necessary to confirm the role and positioning of CD19-directed CAR-T cells within the current MM treatment landscape.