Hematopoietic recovery in patients receiving chimeric antigen receptor T-cell therapy for hematologic malignancies
Hematopoietic recovery in patients receiving chimeric antigen receptor T-cell therapy for hematologic malignancies
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DOI：
10.1182/bloodadvances.2020002509
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发表时间：
2020-08-11
期刊：
影响因子：
7.5
通讯作者：
Mailankody, Sham
中科院分区：
文献类型：
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作者：
Jain, Tania;Knezevic, Andrea;Mailankody, Sham
嵌合抗原受体（CAR） t细胞治疗后促进造血恢复的因素尚未得到很好的研究。在对83例接受CAR - t细胞治疗的恶性血液病患者的分析中，我们描述了造血恢复的模式，并评估了潜在的相关因素。我们纳入了接受axicabtagene ciloleucel （n = 30）或tisagenlecleucel （n = 10）治疗b细胞淋巴瘤的患者，接受CD19-28z CAR - T治疗b细胞急性淋巴细胞白血病的患者（NCT01044069, n = 37），或接受b细胞成熟抗原靶向CAR - T细胞治疗多发性骨髓瘤的患者（NCT03070327, n = 6）。接受CAR - T细胞治疗的未进展、死亡或接受额外化疗的患者在输注后第1个月血红蛋白、血小板、中性粒细胞和白细胞计数“恢复”（根据材料和方法部分的定义）的比率分别为61%、51%、33%和28%，在输注后第3个月分别为93%、90%、80%和59%。单因素分析显示，免疫效应细胞相关神经综合征（ICANS）等级的增加、基线细胞减少、CAR构建和峰值c反应蛋白或铁蛋白水平的升高与1个月时计数完全恢复的可能性较低具有统计学意义；细胞因子释放综合征（CRS）也有类似的趋势。在对基线细胞减少和CAR构建进行调整后，>= 3级CRS或ICANS与1个月时计数未完全恢复显著相关。较高水平的血管内皮生长因子和巨噬细胞衍生的趋化因子，虽然没有统计学意义，但在1个月时计数没有完全恢复。这需要在更大规模的前瞻性研究中进一步研究。
Factors contributing to hematopoietic recovery following chimeric antigen receptor (CAR) T-cell therapy have not been well studied. In an analysis of 83 patients with hematologic malignancies treated with CAR T-cell therapy, we describe patterns of hematopoietic recovery and evaluate potentially associated factors. We included patients who received axicabtagene ciloleucel (n = 30) or tisagenlecleucel (n = 10) for B-cell lymphoma, CD19-28z CAR T therapy for B-cell acute lymphoblastic leukemia (NCT01044069; n = 37), or B-cell maturation antigen targeting CAR T cells for multiple myeloma (NCT03070327; n = 6). Patients treated with CAR T cells who had not progressed, died, or received additional chemotherapy had "recovered" (per definition in Materials and methods section) hemoglobin, platelet, neutrophil, and white blood cell counts at rates of 61%, 51%, 33%, and 28% at month 1 postinfusion and 93%, 90%, 80%, and 59% at month 3 postinfusion, respectively. Univariate analysis showed that increasing grade of immune effector cell-associated neurological syndrome (ICANS), baseline cytopenias, CAR construct, and higher peak C-reactive protein or ferritin levels were statistically significantly associated with a lower likelihood of complete count recovery at 1 month; a similar trend was seen for cytokine release syndrome (CRS). After adjustment for baseline cytopenia and CAR construct, grade >= 3 CRS or ICANS remained significantly associated with the absence of complete count recovery at 1 month. Higher levels of vascular endothelial growth factor and macrophage-derived chemokines, although not statistically significant, were seen patients without complete count recovery at 1 month. This remains to be studied further in larger prospective studies.