Adjuvant ruxolitinib therapy relieves steroid-refractory cytokine-release syndrome without impairing chimeric antigen receptor-modified T-cell function.
Adjuvant ruxolitinib therapy relieves steroid-refractory cytokine-release syndrome without impairing chimeric antigen receptor-modified T-cell function.
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DOI：
10.2217/imt-2020-0116
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发表时间：
2020-08
期刊：
影响因子：
2.8
通讯作者：
S. Wei;R. Gu;Yingxi Xu;Xiaoyu Liu;Y. Xing;X. Gong;Chun-lin Zhou;Bing-cheng Liu;Guangji Zhang;Kaiqi Liu;H. Wei;Y. Mi;Min Wang;Ying Wang;Jianxiang Wang
中科院分区：
文献类型：
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作者：
S. Wei;R. Gu;Yingxi Xu;Xiaoyu Liu;Y. Xing;X. Gong;Chun-lin Zhou;Bing-cheng Liu;Guangji Zhang;Kaiqi Liu;H. Wei;Y. Mi;Min Wang;Ying Wang;Jianxiang Wang
目的：尽管许多促炎细胞因子通过涉及 Janus 激酶的细胞内途径促进信号传导，但仍不清楚 Janus 激酶1/2 抑制剂鲁索替尼是否能控制细胞因子释放综合征 (CRS)，而不会对治疗性 T 细胞产生毒性。材料和方法：我们报告了使用鲁索替尼作为辅助疗法治疗一名费城染色体样急性淋巴细胞白血病患者的类固醇难治性 CRS 的成功临床经验，该 CRS 与 CD22/CD19 嵌合抗原受体修饰的 T 细胞序贯输注有关。结果：第一次服用鲁索替尼后，他的症状迅速改善；这与循环促炎指标水平降低有关。他最终实现了微小残留病阴性缓解。讨论：这是首例使用鲁索替尼治疗类固醇难治性CRS的病例；此外，这种干预对嵌合抗原受体修饰的T细胞的抗白血病作用没有明显影响。我们的结果表明鲁索替尼辅助治疗可能是治疗 CRS 的替代治疗方法。
Aim: Although numerous pro-inflammatory cytokines promote signaling via intracellular pathways involving Janus kinases, it remains unclear if ruxolitinib, a Janus kinase1/2 inhibitor, provides control of cytokine-release syndrome (CRS) without toxicity against therapeutic T cells. Materials & methods: We report successful clinical experience using ruxolitinib as adjuvant therapy to treat steroid-refractory CRS, which was related to CD22/CD19 chimeric antigen receptor-modified T cell sequential infusion, in a patient with Philadelphia chromosome-like acute lymphoblastic leukemia. Results: His symptoms improved rapidly after first dose of ruxolitinib; this was associated with reduced levels of circulating pro-inflammatory indicators. He eventually achieved minimal residual disease negative remission. Discussion: This is the first case in which ruxolitinib was used to treat steroid-refractory CRS; furthermore, this intervention had no apparent impact on the antileukemic actions of the chimeric antigen receptor-modified T cells. Our results suggest that adjuvant ruxolitinib therapy may be an alternative therapeutic approach for the management of CRS.