The impact of end-of-consolidation measurable residual disease in the era of novel pediatric leukemia therapy.

Abstract

259 Background: The introduction of blinatumomab (BLINA) has improved event-free survival (EFS) and overall survival (OS) in pediatric patients with high-risk B-cell acute lymphoblastic leukemia (ALL). In patients with post-induction measurable residual disease (MRD) positivity, BLINA may serve as a safe bridging therapy to hematopoietic cell transplantation (HCT). However, little is known about the impact of end-of-consolidation (EoC) MRD on outcomes in high-risk pediatric ALL in the current BLINA-incorporated treatment era. Methods: We retrospectively enrolled pediatric patients diagnosed with high-risk B-cell ALL between February 2022 and December 2024 at Chang Gung Memorial Hospital. Patients were categorized into EoC MRD-negative and EoC MRD-positive groups. Outcomes of interest included EFS, OS, and BLINA-related adverse events (AEs). Results: The cohort consisted of 15 patients. With a median follow-up of 24 months, the observed 2-year EFS and OS rates were 71.5% and 86.7%, respectively. Based on EoC MRD status, 8 patients were classified as EoC MRD-negative and 7 as EoC MRD-positive. Baseline characteristics were comparable between the two groups. Higher relapse (57.1% vs. 0%, P = 0.0256) and mortality (28.6% vs. 0%, P = 0.2) rates were observed in the EoC MRD-positive group. The 2-year EFS was significantly higher in the EoC MRD-negative group (100% vs. 42.9%, P = 0.02). No high-grade short-term or long-term BLINA-related AEs were observed in either group. Conclusions: Achieving EoC MRD negativity was associated with sustained remission and improved survival in high-risk pediatric B-cell ALL treated with early intensification chemotherapy and BLINA. EoC MRD assessment may help identify patients who can maintain disease control without HCT. Comparisons between EoC MRD-positive and EoC MRD-negative groups. EoC MRD-positive(N= 7) EoC MRD-negative(N = 8) P value Age (years) 7.1 5.4 0.3969 Sex >0.9999 Male 5 5 Female 2 3 Karyotype 0.3203 Hyperdiploidy 0 2 Adverse 2 1 Others 5 5 Molecular alterations 0.3971 ETV6::RUNX1 0 2 BCR::ABL1 1 3 PAX5-altered 1 0 ZNF384 1 1 KMT2A 1 0 No detectable alteration 3 2 Relapse events 57.1% 0% 0.0256* EFS (months) 19 22 0.3778 Survival events 71.4% 100% 0.2 OS (months) 32 22 0.9319 Abbreviations: EFS, event-free survival; EoC, end-of-consolidation; MRD, measurable residual disease; OS, overall survival; *P value <0.05.