Improved survival and MRD remission with blinatumomab vs. chemotherapy in children with first high-risk relapse B-ALL
Abstract
For children with high-risk, first-relapse B-cell precursor acute lymphoblastic leukemia (B-ALL), allogeneic hematopoietic stem cell transplantation (alloHSCT) after achieving a second complete remission (CR) remains the best, potentially curative treatment. In addition, a minimal residual disease (MRD)-negative status at the end of consolidation is an important prognostic indicator as demonstrated in the Children's Oncology Group Studies AALL1131 (high risk) and AALL0932 (standard risk), and ALLR3 and ALL-REZ BFM 2002 studies.
Blinatumomab, a CD3/CD19-directed bispecific T-cell engager (BiTE(R)) molecule, demonstrated a favorable benefit-risk profile prior to/after alloHSCT in patients with relapsed/refractory B-ALL in clinical trials and real-world experience studies, with early termination of enrollment in phase 3 trials in young adults and children because of blinatumomab benefit [4, 6]. In the phase 3 trial in pediatric high-risk, first-relapse B-ALL, blinatumomab consolidation pre-alloHSCT resulted in improved event-free survival (EFS) and MRD remission vs. chemotherapy, with EFS benefit consistently found in all subgroups, including those with extramedullary disease and very early relapse (<18 months) [6].
Enrollment was terminated for EFS benefit of blinatumomab (p < 0.001) per independent data monitoring committee's (DMC) recommendation based on the July 2019 datacut. Follow-up data presented here are from September 2021, with overall survival (OS) benefit becoming apparent with longer follow-up.