Adjuvant ruxolitinib therapy relieves steroid-refractory cytokine-release syndrome without impairing chimeric antigen receptor-modified T-cell function

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. 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. 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. 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.