Blinatumomab combined with low-dose chemotherapy and TKI as first-line induction for newly diagnosed ph+ b-ALL: Improved efficacy and reduced toxicity

Abstract

Abstract Introduction : Ph+ B-ALL, characterized by the BCR-ABL1 fusion gene, accounts for 20-30% of adult ALL and has historically had a poor prognosis. Although the combination of tyrosine kinase inhibitors (TKIs) with intensive chemotherapy has improved complete remission (CR) rates, significant hematologic toxicity and high relapse rates persist, compromising outcomes, particularly in older adults and patients with comorbidities. Blinatumomab, a CD19/CD3 bispecific T-cell engager (BiTE®) antibody, mediates T-cell-directed lysis of leukemic cells and demonstrates efficacy in relapsed/refractory disease, offering a valuable therapeutic option. We compared the efficacy and safety of first-line induction therapy with blinatumomab plus low-dose chemotherapy and TKI versus conventional chemotherapy plus TKI as initial induction in newly diagnosed Ph+ B-ALL. Methods : Adults with newly diagnosed Ph+ B-ALL confirmed by cytogenetics/FISH and/or BCR-ABL PCR were enrolled. Patients were assigned to two induction therapy groups:< 1. ​​Blinatumomab Group​​: Received reduced-intensity chemotherapy (vincristine 2 mg IV days 1, 8, 15, 22; prednisone 1 mg/kg/day days 1-14) combined with TKI. Blinatumomab was administered via continuous intravenous infusion beginning day 15 (9 µg/day days 15-20; escalated to 28 µg/day days 21-42). 2. Conventional Chemotherapy Group​​: Received the VICP regimen (vincristine 2 mg IV days 1, 8, 15, 22; idarubicin 8 mg/m² IV days 1-3; cyclophosphamide 750 mg/m² IV day 1; prednisone 1 mg/kg/day days 1-28) with TKI. Following achievement of complete remission (CR) in both treatment groups, subsequent therapy phases (consolidation, maintenance, and central nervous system prophylaxis) were uniformly administered according to the Chinese Adult Lymphoblastic Leukemia Collaborative Group 2008 protocol (CALLG2008). The primary endpoint was MRD negativity rate; secondary endpoints included progression-free survival (PFS), overall survival (OS), relapse rate and safety. Results: The median age was 51.1 years in the blinatumomab group (n=11) and 42.6 years in the conventional chemotherapy group (n=13). All 24 patients attained CR after one cycle of induction chemotherapy. The MRD negativity rate showed a trend toward improvement in the blinatumomab group compared with the conventional chemotherapy group (81.8% [9/11] vs. 46.2% [6/13], p = 0.072). The median BCR/ABL gene level in the blinatumomab group was 0.10 (range: 0.00–0.56), as opposed to 2.13 (range: 0.25–9.21) in the conventional chemotherapy group. The mean log reduction in the BCR/ABL gene level in the blinatumomab group was 3.09±0.95, which was greater than in the conventional chemotherapy group (1.64±0.83)(p=0.001). At a median follow-up of ~12 months, no relapses occurred in the blinatumomab group vs. 5 relapses (38.5%) in the conventional group. Blinatumomab demonstrated reduced hematologic toxicity: shorter neutropenia duration (2.8 ± 2.4 vs. 6.2 ± 4.4 days, p=0.033), lower bleeding incidence (0% vs. 53.8%, p=0.006), and fewer infections (36.4% vs. 69.2%, p=0.107). Transfusion requirements were also lower (median platelet units: 1.61 ± 1.63 vs. 4.33 ± 2.90, p=0.009; RBC units: 2.14 ± 2.07 vs. 6.15 ± 4.85, p=0.015). Two patients (18.2%) experienced Grade 1 cytokine release syndrome (CRS; fever only), with no Grade ≥2 CRS or immune effector cell-associated neurotoxicity syndrome (ICANS). Conclusions：Blinatumomab combined with low-dose chemotherapy and TKIs as first-line induction therapy in Ph+ B-ALL achieves superior MRD negativity, lower relapse rates, and reduced hematologic toxicity compared to conventional chemotherapy. These findings support further investigation in larger trials to confirm clinical benefit.