多发性骨髓瘤患者CAR-T治疗后细胞因子释放综合征的相关预警指标分析

Analysis of Related Early Warning Indexes of Cytokine Release Syndrome in Multiple Myeloma Patients after CAR-T Treatment

目的:探讨复发难治性(R/R)多发性骨髓瘤(MM)患者接受嵌合抗原受体T细胞(CAR-T)免疫治疗后,患者外周血铁蛋白、C反应蛋白(CRP)、乳酸脱氢酶(LDH)、白细胞介素6(IL-6)水平与细胞因子释放综合征(CRS)的相关性。方法:入组28例R/R MM患者在氟达拉滨和环磷酰胺为基础的预处理化疗后,接受各1×10^(6)/kg的人源化CDl9 CAR-T及鼠源性B细胞成熟抗原CAR-T细胞治疗。输注细胞30 d内定期检测外周血铁蛋白、CRP、LDH及IL-6浓度,分析CRS的严重程度与以上指标的相关性。结果:28例患者中,27例(96.4%)发生CRS,1-2级CRS为24例(85.7%),3-5级为3例(10.7%)。27例患者CRS严重程度分级与其外周血铁蛋白、CRP、LDH及IL-6峰值呈正相关关系(r1=0.511,r2=0.375,r3=0.480,r4=0.632)。3-5级CRS患者的外周血铁蛋白、CRP、LDH及IL-6中位峰值均明显高于0-2级的CRS患者,差异有统计学意义。结论:R/R MM患者接受CAR-T细胞治疗后,CRS发生率较高,但大部分是1级或2级。患者的CRS严重程度与外周血铁蛋白、CRP、LDH及IL-6水平呈正相关。

Objective: To investigate the relationship between the levels of ferritin, C-reactive protein(CRP), lactate dehydrogenase(LDH) and interleukin-6(IL-6) in peripheral serum and cytokine release syndrome(CRS) in patients with relapse and/or refractory multiple myeloma(R/R MM) after receiving chimeric antigen receptor T cells(CAR-T)immunotherapy. Methods: Twenty-eight patients with R/R MM were treated with 1×10^(6)/kg humanized CD19 CAR-T and mouse B cell maturation antigen CAR-T cells after pretreatment chemotherapy based on fludarabine and cyclophosphamide.The concentrations of ferritin, CRP, LDH, and IL-6 in peripheral blood were measured regularly within 30 days after infusion, and the correlation between severity of CRS and above indexes was analyzed. Results: Among the 28 patients,27 cases(96.4%) developed CRS, 24 cases(85.7%) in 1-2 grade CRS and 3 cases(10.7%) in 3-5 grade. The severity grade of CRS of 27 patients was positively correlated with the peak values of ferritin, CRP, LDH, and IL-6 in peripheral blood(r1=0.511, r2=0.375, r3=0.480, r4=0.632). The median peak values of ferritin, CRP, LDH and IL-6 in peripheral serum of patients with grade 3-5 CRS were significantly higher than those in patients with grade 0-2 CRS. Conclusion: After receiving CAR-T cellular immunotherapy, the incidence of CRS in patients with R/R MM is higher, but most of them are in grade 1 or 2. The severity of CRS is positively correlated with the levels of ferritin, CRP, LDH and IL-6 in peripheral blood.