Objective: To observe the characteristics of the evolution of liver indexes in patients with relapsed/refractory multiple myeloma (RRMM) treated with CAR-T-cells based on BCMA. Methods: Retrospective analysis was performed of patients with RRMM who received an infusion of anti-BCMA CAR-T-cells and anti-BCMA combined with anti-CD19 CAR-T-cells at our center between June 1, 2019, and February 28, 2023. Clinical data were collected to observe the characteristics of changes in liver indexes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and direct bilirubin (DBIL) in patients, and its relationship with cytokine-release syndrome (CRS) . Results: Ninety-two patients were included in the analysis, including 41 patients (44.6%) in the group receiving a single infusion of anti-BCMA CAR-T-cells, and 51 patients (55.4%) in the group receiving an infusion of anti-BCMA combined with anti-CD19 CAR-T-cells. After infusing CAR-T-cells, 31 patients (33.7%) experienced changes in liver indexes at or above grade 2, which included 20 patients (21.7%) with changes in one index, five patients (5.4%) with changes in two indexes, and six patients (6.5%) with changes in three or more indexes. The median time of peak values of ALT and AST were d17 and d14, respectively, and the median duration of exceeding grade 2 was 5.0 and 3.5 days, respectively. The median time of peak values of TBIL and DBIL was on d19 and d21, respectively, and the median duration of exceeding grade 2 was 4.0 days, respectively. The median time of onset of CRS was d8, and the peak time of fever was d9. The ALT, AST, and TBIL of patients with CRS were higher than those of patients without CRS (P=0.011, 0.002, and 0.015, respectively). CRS is an independent factor that affects ALT and TBIL levels (OR=19.668, 95% CI 18.959-20.173, P=0.001). The evolution of liver indexes can be reversed through anti-CRS and liver-protection treatments, and no patient died of liver injury. Conclusions: In BCMA-based CAR-T-cell therapy for RRMM, CRS is an important factor causing the evolution of liver indexes. The evolution of liver indexes after CAR-T-cell infusion is transient and reversible after treatment.
目的： 观察以B细胞成熟抗原（BCMA）为基础的嵌合抗原受体T细胞（CAR-T）治疗对复发/难治性多发性骨髓瘤（RRMM）患者肝功能的影响。 方法： 纳入2019年6月1日至2023年2月28日输注抗BCMA CAR-T细胞和输注抗BCMA联合抗CD19 CAR-T细胞的92例RRMM患者，回顾性分析其临床资料，观察患者ALT、AST、总胆红素（TBIL）、直接胆红素（DBIL）等指标变化并分析其与细胞因子释放综合征（CRS）的关系。 结果： 纳入92例患者进行分析，单纯输注抗BCMA CAR-T细胞组41例（44.6%），输注抗BCMA联合抗CD19 CAR-T细胞组51例（55.4%）。31例（33.7%）患者输注CAR-T细胞后发生2级以上肝功能指标改变，其中1项指标改变20例（21.7%），2项指标改变5例（5.4%），3项以上指标改变者6例（6.5%）。ALT、AST高峰时间中位数分别为d 17、d 14，超过2级中位持续时间分别为5.0 d和3.5 d；TBIL和DBIL高峰时间分别为d 19、d 21，超过2级时间均为4.0 d。开始发生CRS的中位时间为d8，发热高峰的中位时间为d 9。发生CRS的患者ALT、AST、TBIL高于未发生CRS的患者（P值分别为0.011、0.002和0.015），CRS是ALT、TBIL的影响因素（OR＝19.668，95%CI 18.959~20.173，P＝0.001）。通过抗CRS治疗和保肝治疗，肝功能指标改变可以逆转，无患者死于肝功能异常。 结论： 在以BCMA为基础的CAR-T细胞治疗的RRMM中，CRS是导致肝功能指标改变的重要因素，CAR-T细胞输注后发生的肝功能指标改变呈一过性，治疗后可逆转。.
Keywords: Chimeric antigen receptor T-cell; Liver function; Multiple myeloma.