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

Cancer Med. 2023 Dec;12(24):21978-21984. doi: 10.1002/cam4.6771. Epub 2023 Dec 8.

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.

Keywords: acute lymphoblastic leukemia; blinatumomab; measurable residual disease; next-generation sequencing; pediatric.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Bispecific* / therapeutic use
  • Burkitt Lymphoma* / drug therapy
  • Child
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Neoplasm, Residual / drug therapy
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma* / drug therapy
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma* / genetics
  • Retrospective Studies

Substances

  • blinatumomab
  • Antibodies, Bispecific