接受抗 BCMA CAR-T 细胞治疗的伴髓外病变复发/难治性多发性骨髓瘤患者的临床结局与微环境特征分析

Relapsed/refractory multiple myeloma patients with extramedullary disease (EMD) have unfavorable prognosis and lack effective therapy. Chimeric antigen receptor (CAR) T-cell activities in EMD have yet to be determined; how EMD-specific microenvironment influences the clinical outcomes of CAR T-cell therapy remains of great interest.

In this prospective cohort study, patients with histologically confirmed extra-osseous EMD were enrolled and treated with combined anti-BCMA and anti-CD19 CAR T-cell therapy from May 2017 to September 2023. Thirty-one patients were included in the study.

Overall response occurred in 90. 3% of medullary disease and 64. 5% of EMD (p = . 031). Discrepancies in treatment response were noted between medullary and extramedullary diseases, with EMD exhibiting suboptimal and delayed response, as well as shortened response duration. With a median follow-up of 25. 3 months, the median progression-free and overall survival were 5. 0 and 9. 7 months, respectively. Landmark analysis demonstrated that progression within 6 months post-infusion is strongly associated with an increased risk of death (HR = 4. 58; p = . 029). Compared with non-EMD patients, patients with EMD showed inferior survival outcomes.

Unique CAR-associated local toxicities at EMD were seen in 22. 6% patients and correlated with the occurrence and severity of systemic cytokine release syndrome. To the cutoff date, 65% treated patients experienced EMD progression, primarily in the form of BCMA + progression.

The pretherapy EMD immunosuppressive microenvironment, characterized by infiltration of exhausted CD8 + T cells, was associated with inferior clinical outcomes. CAR T cells have therapeutic activity in relapsed/refractory EMD, but the long-term survival benefits may be limited. EMD-specific microenvironment potentially impacts treatment.

Further efforts are needed to extend EMD remission and improve long-term outcomes.