托珠单抗治疗CAR-T细胞治疗难治复发多发性骨髓瘤后细胞因子释放综合征的疗效

目的:观察托珠单抗治疗嵌合抗原受体修饰的T(CAR-T)细胞治疗难治复发多发性骨髓瘤(multiple myeloma,MM)后细胞因子释放综合征(cytokine release syndrome,CRS)的疗效.方法:以2016年2月至2017年2月西安交通大学第二附属医院血液内科住院的24例CAR-T细胞治疗难治复发MM患者为研究对象,对发生2级以上的CRS患者给予4～8 mg/(kg·d)的托珠单抗治疗,观察其疗效及毒副作用、细胞因子、超敏C反应蛋白(HsCRP)等的变化.结果:24例患者中有21例患者发生了CRS,依据CRS分级标准:1、2级各7例,3级5例,4级2例.CRS患者均表现持续高热,细胞因子及HsCRP明显升高,其中IL-6升高最为显著.14例2级以上CRS患者经托珠单抗治疗后,临床症状明显缓解、体温迅速下降,细胞因子、HsCRP含量逐渐恢复正常,无明显毒副作用发生.结论:托珠单抗在CRS治疗中疗效明显、无明显毒副作用,保证了难治复发MM患者CAR-T治疗的安全性.

Effects of tocilizumab regimen on cytokine release syndrome for patients with relapsed or refractory multiple myeloma treated by CAR-T cell immunotherapy

Objective:To observe the therapeutic effect oftocilizumab on cytokine release syndrome (CRS) for patients with relapsed or refractory multiple myeloma (MM) treated by CAR-T cell immunotherapy.Methods:From February 2016 to February 2017,24 patients with relapsed or refractory multiple myeloma treated by CAR-T cell immunotherapy in the Department of Hematology of Second Affiliated Hospital of Medical College,Xi'an Jiaotong University were included as study subjects.Tocilizumab (4-8 mg/kg·d) was applied on MM patients with grade 2 or above,and the treatment efficacy,side effects,and the changes of hypersensitive C-reactive protein (HsCRP) etc were observed.Results:Twenty-one of the 24 patients suffered from CRS during the CAR-T treatment.According to the CRS classification criteria,7 patients had grade 1 CRS reaction,7 patients with grade 2,5 patients with grade 3,and 2 patients with grade 4.The manifestations of CRS were hyperpyrexia,significant increase in cytokines and HsCRP level with the most obvious increase in IL-6.Fourteen CRS patients with grade 2 or above were treated by tocilizumab and their clinical symptoms were obviously alleviated:the temperature was rapidly decreased and cyto kines and hypersensitive C-reactive protein dropped to normal gradually.In the process of treatment,no obvious side effects were observed.Conclusion:Tocilizumab showed a significant clinical efficacy in the treatment of CRS,which greatly guaranteed the safety of the MM patients in the CAR-T treatment.