Anti-CD19 Monoclonal antibody, clone IJC20 [eFluor® 450]

Globally, there were 509,590 new cases and 248,724 deaths of non-Hodgkin lymphoma (NHL) in 2018. Diffuse large B-cell lymphoma (DLBCL) is the most common type of NHL worldwide. Loncastuximab tesirine (Lonca-T) is a novel antibody-drug conjugate that targets CD19 and is comprised of a humanized monoclonal antibody, a dipeptide linker and a DNA-damaging agent. Lonca-T showed potent cytotoxicity in CD19-expressing human cell lines in vitro, and potent antitumor activity in relevant experimental models in vivo. In a phase II study in patients with relapsed or refractory DLBCL, Lonca-T showed an overall response rate of 46% and complete response in 19% of patients. Currently, there are 2 ongoing phase Ib studies of Lonca-T in combination, i.e., one in DLBCL, mantle cell lymphoma (MCL) or follicular lymphoma patients, and the other in DLBCL or MCL patients. The U.S. Food and Drug Administration has granted orphan drug designation to Lonca-T for the treatment of DLBCL and MCL.

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.