The effectiveness of blinatumomab in clearing measurable residual disease in pediatric B-cell acute lymphoblastic leukemia patients detected by next-generation sequencing

Abstract

Background: Blinatumomab improved survival outcomes in B-cell acute lymphoblastic leukemia (B-ALL) patients with measurable residual disease (MRD) <10−4. However, data on blinatumomab clearing MRD with high sensitivity of 10−6 remain scarce. This study evaluates the effectiveness of blinatumomab in eradicating extremely low level (up to <10−6) of MRD, as detected by next-generation sequencing (NGS), in children with B-ALL. Methods: Patients (n = 19) whose MRD was undetectable by multiparameter flow cytometry (MFC) (sensitivity of 10−4) but detectable by NGS after chemotherapy and followed by blinatumomab consolidation were included retrospectively. Results: After one course of blinatumomab, 13/19 patients (68%) successfully achieved NGS-MRD clearance (undetectable). With a median follow-up of 13.3 months, three of patients who were NGS-MRD positive relapsed within 1.8 months, while another three remained complete remission. Conclusions: Our study was the first to demonstrate that blinatumomab could further eradicate MRD after patients achieve MFC-MRD undetectable in B-ALL patients.