Sun Q, Qi Y K, Qi K M, Yan Z L, Cheng H, Chen W, Zhu F, Sang W, Li D P, Cao J, Shi M, Li Z Y, Xu K L
Hematology Institute of Xuzhou Medical University, Hematology Department of The Affiliated Hospital of Xuzhou Medical University, Jiangsu Provincial Key Laboratory of Bone Marrow Stem Cells, Xuzhou 221002, China.
Zhonghua Xue Ye Xue Za Zhi. 2023 Oct 14;44(10):832-837. doi: 10.3760/cma.j.issn.0253-2727.2023.10.007.
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. 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) . 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 (=0.011, 0.002, and 0.015, respectively). CRS is an independent factor that affects ALT and TBIL levels (=19.668, 95% 18.959-20.173, =0.001). The evolution of liver indexes can be reversed through anti-CRS and liver-protection treatments, and no patient died of liver injury. 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.
观察基于BCMA的CAR-T细胞治疗复发/难治性多发性骨髓瘤(RRMM)患者肝脏指标的演变特征。对2019年6月1日至2023年2月28日在本中心接受抗BCMA CAR-T细胞输注以及抗BCMA联合抗CD19 CAR-T细胞输注的RRMM患者进行回顾性分析。收集临床资料,观察患者丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素(TBIL)和直接胆红素(DBIL)等肝脏指标的变化特征及其与细胞因子释放综合征(CRS)的关系。92例患者纳入分析,其中接受单次抗BCMA CAR-T细胞输注组41例(44.6%),接受抗BCMA联合抗CD19 CAR-T细胞输注组51例(55.4%)。输注CAR-T细胞后,31例患者(33.7%)出现2级及以上肝脏指标变化,其中单项指标变化20例(21.7%),两项指标变化5例(5.4%),三项及以上指标变化6例(6.5%)。ALT和AST峰值的中位时间分别为第17天和第14天,超过2级的中位持续时间分别为5.0天和3.5天。TBIL和DBIL峰值的中位时间分别为第19天和第21天,超过2级的中位持续时间均为4.0天。CRS的中位发病时间为第8天,发热峰值时间为第9天。CRS患者的ALT、AST和TBIL高于无CRS患者(P值分别为0.011、0.002和0.015)。CRS是影响ALT和TBIL水平的独立因素(P = 19.668,95%CI 18.959 - 20.173,P = 0.001)。通过抗CRS和保肝治疗,肝脏指标的演变可逆转,无患者死于肝损伤。在基于BCMA的CAR-T细胞治疗RRMM中,CRS是导致肝脏指标演变的重要因素。CAR-T细胞输注后肝脏指标的演变是短暂的,治疗后可逆转。