Cheng Hai, Shao Lingyan, Wang Dandan, Chen Yegan, Sun Yingjun, Chen Zihan, Liu Jiaying, Wang Xue, Chen Wei, Sang Wei, Qi Kunming, Li Zhenyu, Sun Cai, Shi Ming, Qiao Jianlin, Wu Qingyun, Zeng Lingyu, Zheng Junnian, Li Li, Xu Kailin, Cao Jiang
Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Cancer Institute, Xuzhou Medical University, Xuzhou, China.
Cytotherapy. 2025 Jan;27(1):16-24. doi: 10.1016/j.jcyt.2024.08.007. Epub 2024 Aug 23.
Many studies have demonstrated the effectiveness of chimeric antigen receptor-T (CAR-T) cell therapy for relapsed or refractory multiple myeloma (RRMM), but the hematologic toxicity has not been well characterized.
A total of 111 adults with RRMM who received BCMA CAR-T cells, BCMA + CD19 CAR-T cells or tandem BCMA/CD19 dual-target (BC19) CAR-T cells infusion were enrolled. We characterized cytopenia and hematologic recovery at different time points after CAR-T-cell therapy, analyzed the effect of cytopenia on prognosis and identified the risk factors.
Patients had a high probability of cytopenia, with anemia, neutropenia and thrombocytopenia occurring in 92%, 95% and 73%, respectively. There were 60 (54%) patients had prolonged hematologic toxicity (PHT) after D28. The median hemoglobin and platelet count were significantly lower at D28 post-CAR-T cell therapy than at baseline. Hemoglobin increased to above baseline at D90. The median absolute neutrophil count was lower than baseline at D0 and D28, and it recovered to baseline at D180. The baseline level of lactate dehydrogenase was associated with thrombocytopenia. Extramedullary involvement was associated with hemoglobin recovery, while the baseline level of albumin and types of CAR-T were related to platelet recovery. Patients with anemia at baseline and at D0, D180 and D360 had shorter progression-free survival (PFS), while anemia at D0, D60, D180 and D360 was associated with shorter overall survival (OS). Neutropenia at D0 was associated with shorter PFS and patients with neutropenia at D90 or D180 had shorter OS. Patients with thrombocytopenia at any time had shorter PFS and OS. Compared to patients without PHT, patients with PHT had shorter PFS and OS.
The majority of RRMM patients treated with CAR-T cells experienced cytopenia. Cytopenia occurred at specific time points was associated with a poorer prognosis.
许多研究已证明嵌合抗原受体T（CAR-T）细胞疗法对复发或难治性多发性骨髓瘤（RRMM）有效，但血液学毒性尚未得到充分表征。
共纳入111例接受靶向B细胞成熟抗原（BCMA）的CAR-T细胞、靶向BCMA + CD19的CAR-T细胞或串联BCMA/CD19双靶点（BC19）CAR-T细胞输注的RRMM成年患者。我们对CAR-T细胞治疗后不同时间点的血细胞减少和血液学恢复情况进行了表征，分析了血细胞减少对预后的影响，并确定了风险因素。
患者发生血细胞减少的概率很高，贫血、中性粒细胞减少和血小板减少的发生率分别为92%、95%和73%。60例（54%）患者在第28天后出现长期血液学毒性（PHT）。CAR-T细胞治疗后第28天的血红蛋白和血小板计数中位数显著低于基线水平。血红蛋白在第90天升至基线以上。绝对中性粒细胞计数中位数在第0天和第28天低于基线水平，并在第180天恢复至基线水平。乳酸脱氢酶的基线水平与血小板减少有关。髓外受累与血红蛋白恢复有关，而白蛋白的基线水平和CAR-T细胞类型与血小板恢复有关。基线时以及第0天、第180天和第360天出现贫血的患者无进展生存期（PFS）较短，而第0天、第60天、第180天和第360天出现贫血与总生存期（OS）较短有关。第0天的中性粒细胞减少与较短的PFS有关，第90天或第180天出现中性粒细胞减少的患者OS较短。任何时间出现血小板减少的患者PFS和OS均较短。与无PHT的患者相比，有PHT的患者PFS和OS较短。
大多数接受CAR-T细胞治疗的RRMM患者出现血细胞减少。特定时间点出现的血细胞减少与较差的预后相关。
