决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Comprehensive characterization of cytopenia after chimeric antigen receptor-T cell infusion in patients with relapsed or refractory multiple myeloma.
大多数接受CAR-T细胞治疗的RRMM患者出现了血细胞减少。在特定时间点出现的血细胞减少与较差的预后相关。
许多研究已证明CAR-T(CAR-T)细胞疗法对复发或难治性多发性骨髓瘤(RRMM)的有效性,但其血液学毒性尚未得到充分表征。
共纳入111例接受BCMA CAR-T细胞、BCMA + CD19 CAR-T细胞或串联BCMA/CD19双靶点(BC19)CAR-T细胞输注的RRMM成人患者。我们描述了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,分析了血细胞减少对预后的影响,并确定了危险因素。
患者发生血细胞减少的概率较高,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%。有60例(54%)患者在D28后出现延长的血液学毒性(PHT)。CAR-T细胞治疗后D28时,中位血红蛋白和血小板计数显著低于基线水平。血红蛋白在D90时升至基线以上。中位绝对中性粒细胞计数在D0和D28时低于基线,并在D180时恢复至基线水平。基线乳酸脱氢酶水平与血小板减少相关。髓外受累与血红蛋白恢复相关,而基线白蛋白水平和CAR-T类型与血小板恢复相关。基线和D0、D180、D360时存在贫血的患者无进展生存期(PFS)较短,而D0、D60、D180和D360时存在贫血与较短的总生存期(OS)相关。D0时中性粒细胞减少与较短的PFS相关,D90或D180时中性粒细胞减少的患者OS较短。任何时间存在血小板减少的患者PFS和OS均较短。与无PHT的患者相比,PHT患者的PFS和OS较短。
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: The majority of RRMM patients treated with CAR-T cells experienced cytopenia. Cytopenia occurred at specific time points was associated with a poorer prognosis.
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