Background: B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor T-cell (CAR-T) therapy has demonstrated substantial efficacy in relapsed and/or refractory multiple myeloma. While toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) have been well characterized, the incidence and clinical consequences of the coagulopathy associated with CRS remain underexplored.Methods: We conducted a prospective analysis of 108 adult patients with multiple myeloma or light chain amyloidosis treated with the academic anti-BCMA CAR-T HBI0101 in a single-center trial (NCT04720313). Coagulopathy was evaluated via serial fibrinogen measurements, with hypofibrinogenemia defined as <200 mg/dL and severe coagulopathy as <100 mg/dL. Laboratory markers, tocilizumab and blood product use, and thrombotic and bleeding complications were recorded. Patients received a short (3-day) or extended course of enoxaparin thromboprophylaxis as well as fresh frozen plasma in cases of severe coagulopathy.Results: CRS grades 1–3 occurred in 100 patients (93%). Hypofibrinogenemia was observed in 79 patients (73%), including 20 (19%) with severe coagulopathy. Fibrinogen levels were significantly associated with CRS severity (p< 0.001), number of tocilizumab doses (p< 0.001), peak levels of the inflammation markers LDH (p= 0.001) and ferritin (p= 0.006), and neutropenia (p= 0.33). Five thrombotic events (4.6%) and three minor bleeding events (2.7%) occurred within 3 months post-CAR-T infusion and were not associated with degree of coagulopathy or CRS. No cases of major bleeding or fatal thrombosis occurred.Conclusions: CRS-related coagulopathy is common following BCMA-targeted CAR-T treatment and correlates closely with CRS severity. Despite the high rate of laboratory coagulopathy, thrombosis and bleeding events were infrequent, suggesting the benefit of the prophylactic strategies used.
背景：靶向B细胞成熟抗原（BCMA）的嵌合抗原受体T细胞（CAR-T）疗法在复发和/或难治性多发性骨髓瘤中显示出显著疗效。尽管细胞因子释放综合征（CRS）和免疫效应细胞相关神经毒性综合征（ICANS）等毒性反应已得到充分描述，但与CRS相关的凝血功能障碍的发生率及临床后果仍待深入探究。 方法：我们在一项单中心试验（NCT04720313）中对108例接受学术性抗BCMA CAR-T HBI0101治疗的多发性骨髓瘤或轻链淀粉样变性成人患者进行了前瞻性分析。通过系列纤维蛋白原检测评估凝血功能障碍，低纤维蛋白原血症定义为<200 mg/dL，严重凝血功能障碍定义为<100 mg/dL。记录实验室标志物、托珠单抗及血液制品使用情况，以及血栓和出血并发症。患者接受短期（3天）或延长疗程的依诺肝素血栓预防，严重凝血功能障碍者加用新鲜冰冻血浆。 结果：100例患者（93%）发生1-3级CRS。79例患者（73%）出现低纤维蛋白原血症，其中20例（19%）为严重凝血功能障碍。纤维蛋白原水平与CRS严重程度（p<0.001）、托珠单抗使用次数（p<0.001）、炎症标志物乳酸脱氢酶峰值（p=0.001）和铁蛋白峰值（p=0.006）以及中性粒细胞减少（p=0.33）显著相关。CAR-T输注后3个月内发生5例血栓事件（4.6%）和3例轻微出血事件（2.7%），均与凝血功能障碍程度或CRS无关。未发生大出血或致死性血栓事件。 结论：BCMA靶向CAR-T治疗后CRS相关凝血功能障碍较为常见，且与CRS严重程度密切相关。尽管实验室检测凝血功能障碍发生率较高，但血栓和出血事件罕见，提示所采用的预防策略具有临床获益。
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