Rituximab improves Clinical Outcomes of CAR-T therapy for r/r B-ALL via sensitizing Leukemia Cells to CAR-T-mediated cytotoxicity and reducing CAR-T exhaustion

Abstract

Abstract Despite chimeric antigen receptor (CAR) T-cell therapy has achieved great advances in recent year, approximately 50% of relapsed/refractory B cell acute lymphoblastic leukemia (r/r B-ALL) patients treated with CAR-T experience relapse 6 months post CAR-T treatment. CD20 express on 30 to 50% of B-ALL, which makes CD20 Monoclonal Antibody as one of the potential therapy strategies to decrease the tumor burden and improve the efficacy of CAR-T therapy. Adding Rituximab to chemotherapy protocol had been demonstrated to improve the outcome for CD20-positive ALL. However, rare study explored the influence of Rituximab combined with CAR-T therapy. We retrospectively analyzed 20 r/r B-ALL patients who received CAR-T therapy, all of whom had failed multiple lines of therapy. Before CAR-T infusion, we administered Rituximab to 10 patient with high CD20 expression at a dose of 375mg/m2 for 1 day. Meanwhile, we selected 10 patients with the comparable features who underwent CAR-T treatment without Rituximab in the same period as the control group. In vitro, the surface molecule expression and killing of CAR-T post Rituximab-treated B-ALL cells co-incubated with CAR-T cells were detected by flow cytometry. Rituximab combined with CAR-T therapy was effective for improving the long-term outcome of B-ALL patients who have failed multiple lines of therapy. In vitro, we observed that rituximab potentially improved CAR-T efficacy by sensitizing Leukemia Cells to CAR T-mediated cytotoxicity and reducing CAR-T exhaustion.