Application of Blinatumomab, a Bispecific T Cell Engager, in Treating Refractory Immune-Mediated Kidney Diseases in Pediatric Patients

Background: B-T cell collaboration drives immune-mediated inflammation. Historically, B-T co-interaction was disrupted by depleting B cells or inhibiting T cells. Most patients with immune-mediated kidney disease (IMKD) benefit from B cell depletion (BCD). Refractory IMKD remains a challenge for patients with incomplete BCD. Here, we explore the potential of novel therapies using effector T cells to kill B cells, aiming to address refractory IMKD in children. Methods: We introduced a low dose of CD19×CD3 BiTE blinatumomab into severe multidrug-resistant children with IMKD. Blinatumomab was administered at starting dose of 5 μg/m2/day as continuous infusion over 4 days (total dose of 35 μg). During weeks 2 through 4, the patients received 1-3 cycles of 4-day blinatumomab infusion at a dose of 15 μg/m2/day. All patients were followed up for at least 3 months. Results: Five patients (4 LN, 1 IC-MPGN) were analyzed, median age was 13.4 years old, and median baseline eGFR was 116.0 mL/min/1.73 m2. The treatment was well-tolerated, with a transient increase in body temperature observed during the first week; however, there were no indications of clinically significant cytokine-release syndrome and ICANS. Blinatumomab led to a rapid improvement in proteinuria and hematuria in all patients, and reduced autoantibodies. Deep multiparametric flow cytometry analysis of lymphoid subsets documented an immune reset with depletion of IgD+ naïve B cells and a rise in the proportions of plasmablasts. Conclusion: Here, we present the pioneering use of blinatumomab in pediatric patients with severe refractory immune-mediated kidney disease, offering a promising alternative for such challenging cases. Funding: Government Support – Non-U.S.Table 1. Baseline characteristics and clinical efficacy of BiTE in pediatric patients with refractory immune-mediated kidney disease