Reduced-dose chemotherapy followed by blinatumomab for newly diagnosed philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia: a propensity-matched comparison with hyper-CVAD

Background Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia (Ph-negative BCP-ALL) accounts for a significant portion of adult cases. Blinatumomab, a bispecific T-cell engager, has shown efficacy in relapsed or refractory BCP-ALL, but its role in induction therapy with reduced-dose chemotherapy is being explored. Methods In this retrospective study, 35 newly diagnosed Ph-negative BCP-ALL patients received reduced-dose chemotherapy followed by two weeks of blinatumomab (RDC-Blinatumomab-2W) as part of our previous clinical trial. These patients were compared with a propensity score-matched historical control group of 35 patients treated with the hyper-CVAD regimen. The primary endpoint was composite complete remission (CRc); secondary endpoints included minimal residual disease (MRD) negativity, adverse events, and survival outcomes. Results After matching, both groups had 17 patients (49%) with poor-risk genetic aberrations. The RDC-Blinatumomab-2W group achieved higher CRc rates compared to controls (94% vs. 63%, p = 0.0074) and greater MRD negativity (86% vs. 43%, p = 0.0015). They experienced fewer Grade 3-4 thrombocytopenia cases (62% vs. 89%, p = 0.012), fewer serious infections (23% vs. 54%, p = 0.019), and higher 1-year overall survival rates (97.1% vs. 58.9%, p < 0.001). The 1-year progression-free survival was also superior in the RDC-Blinatumomab-2W group (82.2% vs. 44.6%, p = 0.002). Conclusion Reduced-dose chemotherapy followed by blinatumomab improves remission rates, MRD negativity, and survival while reducing adverse events in newly diagnosed Ph-negative BCP-ALL patients compared to hyper-CVAD. This regimen offers a safer and more effective induction therapy option, warranting further investigation in larger trials.