复发难治性多发性骨髓瘤患者CAR-T细胞治疗后CRS的发热特征和生物标志物变化

Fever Characteristics and Biomarker Changes of CRS in Patients with Relapsed/Refractory Multiple Myeloma after CAR-T Cell Therapy

目的:探讨嵌合抗原受体T细胞(CAR-T)免疫疗法治疗复发难治性多发性骨髓瘤(R/R MM)患者后,患者的临床特征、发热特征和血清生物标志物与细胞因子释放综合征(CRS)的关系,以便更好地预测、治疗CRS。方法:纳入2017年6月至2021年11月期间在徐州医科大学附属医院接受CAR-T治疗的104例R/R MM患者,分析患者的临床特征、发热特征和血清生物标志物与CRS严重程度之间的关系。结果:104例接受CAR-T治疗的R/R MM患者中,有8例(7.7%)未观察到CRS发生,96例(92.3%)发生CRS。具有高危细胞遗传学特征的患者发生CRS的风险较高(P=0.040),而既往接受过自体造血干细胞移植(ASCT)的患者发生CRS的风险较低(P=0.004)。1-2级和3-5级CRS患者之间发热持续时间存在显著差异(P=0.006)。采用不同处理方案的患者发热最高温度有差异(P=0.001)。发生CRS患者总蛋白的下降程度较未发生CRS的患者明显(P=0.002)。CAR-T输注一个月内,3-5级CRS患者白蛋白恢复程度较0-2级CRS患者低(P=0.037)。相较于1-2级CRS患者,3-5级CRS患者在CAR-T细胞输注后观察到明显的心率升高(P=0.013),同时IL-6、C-反应蛋白(CRP)和血清铁蛋白(SF)也有明显的升高(P=0.007,P<0.001,P=0.003)。结论:高危细胞遗传学特征是发生严重CRS的危险因素。较长的发热持续时间是严重CRS的临床特征。CRP能更好地反映CRS的严重程度。

Objective:To investigate the correlation of the clinical characteristics,fever characteristics,serum biomarkers with cytokine release syndrome(CRS)in patients with relapsed/refractory multiple myeloma(R/R MM)treated with chimeric antigen receptor T cell(CAR-T)immunotherapy.Methods:104 R/R MM patients who received CAR-T cell therapy at the Affiliated Hospital of Xuzhou Medical University from June 2017 to November 2021 were included,and the correlations of their clinical characteristics,fever characteristics,serum biomarkers with the severity of CRS were analyzed.Results:Among 104 R/R MM patients receiving CAR-T treatment,no CRS was observed in 8 cases(7.7%),and 96 cases(92.3%)developed CRS.Patients with high-risk cytogenetics had a higher risk of developing CRS(P=0.040),while patients who had previously received autologous hematopoietic stem cell transplantation(ASCT)had a lower risk of developing CRS(P=0.004).There was a significant difference in the duration of fever between patients with grade 1-2 and grade 3-5 CRS(P=0.006).The highest body temperature varied among patients with different treatment regimens(P=0.001).The decrease in total protein in patients with CRS was more significant than in patients without CRS(P=0.002).Within one month after CAR-T cell infusion,the degree of albumin recovery in patients with grade 3-5 CRS was lower than that in patients with grade 0-2 CRS(P=0.037).Compared to patients with grade 1-2 CRS,patients with grade 3-5 CRS showed a significant increase in heart rate after CAR-T cell infusion(P=0.013),while IL-6,C-reactive protein(CRP),and serum ferritin(SF)also showed significant increases(P=0.007,P<0.001,P=0.003).Conclusion:High-risk cytogenetics is a risk factor for severe CRS.Long duration of fever is a clinical characteristic of severe CRS.CRP can better reflect the severity of CRS.