Blinatumomab combined with low-dose chemotherapy and tyrosine kinase inhibitors as first-line induction for newly diagnosed Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia: improved efficacy and reduced toxicity

Blinatumomab联合低剂量化疗和酪氨酸激酶抑制剂作为新诊断的费城染色体阳性B细胞急性淋巴细胞白血病的一线诱导治疗:疗效提高,毒性降低

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Abstract

BACKGROUND: While blinatumomab has demonstrated substantial efficacy in relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), the therapeutic potential of combining blinatumomab with tyrosine kinase inhibitors (TKIs) and low-dose chemotherapy as frontline induction for newly diagnosed Philadelphia chromosome-positive B-ALL (Ph + B-ALL) remains systematically underexplored. This study aims to evaluate the efficacy and safety of blinatumomab in combination with low-dose chemotherapy for induction treatment of newly diagnosed Ph + B-ALL. METHODS: A retrospective analysis was performed on 24 newly diagnosed cases of Ph + B-ALL admitted to the Department of Hematology at our institution, between April 2023 and April 2025. RESULT: 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]). The median BCR::ABL1 level was 0.10 (range: 0.00-0.56) in the blinatumomab group versus 2.13 (range: 0.25-9.21) in the conventional chemotherapy group. The mean log reduction in the BCR::ABL1 gene level in the blinatumomab group was 3.09 ± 0.95, which was greater than in the conventional chemotherapy group (1.64 ± 0.83). At a median follow-up of approximately 13.8 months, no relapses occurred in the blinatumomab group versus 5 relapses (38.5%) in the conventional group. We documented a significant improvement in 12-month disease-free survival (DFS) rate with the blinatumomab regimen (90.9%) compared to conventional chemotherapy (46.2%). Patients receiving blinatumomab experienced markedly reduced hematologic toxicity, manifested by a shorter duration of neutropenia (2.8 ± 2.4 vs. 6.2 ± 4.4 days), a lower incidence of bleeding (0% vs. 53.8%), and a lower rate of infections (36.4% vs. 69.2%). This improved safety profile was accompanied by a significantly lower transfusion burden, as evidenced by the consumption of fewer units of platelets (1.61 ± 1.63 vs. 4.33 ± 2.90) and red blood cells (2.14 ± 2.07 vs. 6.15 ± 4.85). CONCLUSION: Blinatumomab combined with low-dose chemotherapy and TKIs demonstrated a trend toward improved 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.

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