Blinatumomab demonstrates MRD eradication in MRD-positive/chemotherapy-delayed pediatric B-ALL and high response in relapsed/refractory cases: a multicenter cohort study.
AI interpretation is pending for this paper.
Open original publication →What the AI sees
Not AI summarized yet.
Research significance
Pending deeper interpretation.
Source abstract
BACKGROUND: Blinatumomab, a bispecific T-cell engager targeting CD3+ and CD19+, promotes T cell-mediated cytotoxicity against B-cell precursor acute lymphoblastic leukemia (B-ALL). While its efficacy is established in relapsed/refractory (R/R) disease, its role as preemptive therapy for minimal residual disease (MRD)-positive patients or those experiencing chemotherapy delays remains undefined. Predictors of treatment failure also require further investigation. METHODS: In this multicenter retrospective study, 105 patients who received blinatumomab were enrolled. Of these, 30 had R/R ALL, 21 were in complete remission (CR) with MRD positivity (CR-MRDpos), and 54 experienced chemotherapy delays. Eight patients received blinatumomab directly as reinduction therapy and 22 patients received burden-reduction chemotherapy prior to blinatumomab. In total, 11 children were in R/R status and 40 were in CR-MRDpos before treatment. Patients were subsequently bridged to stem cell transplantation, chimeric antigen receptor T-cell therapy (CAR-T), or protocol continuation. Treatment response was analyzed across CR-MRDpos, R/R, and CR with MRD negativity (CR-MRDneg). Immune reconstitution profiles (T-cell subsets, cytokine dynamics), cytogenetic markers, and clinical outcomes were assessed to identify predictors of treatment resistance. RESULTS: The CR rate was 81.8% in R/R and 82.5% in CR-MRDpos patients (P = 1.000). Of 74 courses with CR-MRDneg, 73 remained MRD-negative during treatment. Univariate analysis revealed poor cytogenetics (P = 0.0001), CD19+ B-cell loss (P = 0.046), and BCR-ABL1 positivity (P = 0.002) as predictors of poor response. Cox regression analysis identified high MRD (P = 0.014), BCR/ABL1 (P = 0.065), and poor cytogenetics (P = 0.025) as independent risk factors. Blinatumomab significantly increased CD3+ T cells [0.96 (0.03-3.79) to 1.13 (0.26-7.74) ×109/L, P = 0.016], along with CD4+ [0.35 (0.01-1.39) to 0.47 (0.07-2.94) ×109/L] and CD8+ T cells [0.41 (0.01-2.39) to 0.56 (0.07-6.07) ×109/L] (P = 0.005 and P = 0.006, respectively).The 1-year event-free survival for CR-MRDneg, CR-MRDpos, and R/R patients was 97.8% ± 2.2%, 86.7% ± 6.2%, and 73.3% ± 8.1%, respectively (P = 0.001), while overall survival was 97.8% ± 2.2%, 100%, and 93.3% ± 4.6% (P = 0.029). CONCLUSIONS: Blinatumomab effectively clears MRD as preemptive therapy and serves as a bridging strategy during chemotherapy delays in pediatric B-ALL, while maintaining high response rates in R/R cases.