Adjuvant Ruxolitinib Therapy Relieves Steroid-Refractory Cytokine-Release Syndrome without Impairing Chimeric Antigen Receptor-Modified T-Cell Function
Shuning Wei, Runxia Gu, Yingxi Xu, Xiaoyu Liu, Yanyan Xing, Xiaoyuan Gong, Chunlin Zhou, Bingcheng Liu, Guangji Zhang, Kaiqi Liu, Hui Wei, Yingchang Mi, Min Wang, Ying Wang, Jianxiang Wang
Abstract
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.