The combination of alternating reduced-dose blinatumomab and hyper-CVAD as consolidation therapy in patients with newly-diagnosed adult B-cell acute lymphoblastic leukemia.

BACKGROUND: Blinatumomab has gained attention for its effectiveness in improving overall survival in relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) and eradicating minimal residual disease (MRD). OBJECTIVES: We conducted a retrospective study to assess whether combining reduced-dose blinatumomab with chemotherapy for consolidation could improve outcomes in newly diagnosed B-ALL. DESIGN: Patients with Philadelphia chromosome (Ph)-positive or Ph-negative B-ALL who achieved complete remission (CR) after induction received consolidation therapy consisting of blinatumomab (cycle 1, 3, 5, and 7) and hyper-CVAD (course B for cycles 2 and 6; course A for cycle 4 and 8). After completion of the cycle 2, the decisions to continue treatment or receive hematopoietic stem-cell transplantation were made based on multiple factors. METHODS: The final endpoint was molecular remission, overall survival (OS), relapse-free survival (RFS). Molecular remission referred to MRD-related methods, including MFC (multiparameter flow cytometry)-based MRD, next generation sequencing (NGS)-based MRD, and complete molecular remission (CMR). Meanwhile, we assessed the safety profile of this combination regimen, including adverse events such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). RESULTS: 32 newly diagnosed B-ALL patients (14 Ph+ B-ALL and 18 Ph- B-ALL) achieving CR were analyzed. At the time of study inclusion, 12 Ph+ B-ALL and 12 Ph- B-ALL patients were MFC-MRD negative, and 5 Ph+ B-ALL patients achieved CMR. After the first blinatumomab consolidation and hyper-CVAD B cycle, seven additional patients (one Ph+ B-ALL and six Ph- B-ALL) achieved MFC-MRD negativity, and six additional Ph+ B-ALL patients achieved CMR. With a median follow-up of 16.5 months, the overall rate of MFC-MRD was 96.88% (Ph+ B-ALL 92.86% and Ph- B-ALL 100%), and CMR was 78.57%. The estimated RFS and OS rates at 30 months for whole patients were 83.5% (95% CI, 79.1%-100%) and 96.8% (95% CI, 90.8%-100%), respectively. The most common adverse events were observed during chemotherapy cycles due to myelosuppression. Eight patients developed a grade 1-2 blinatumomab-related CRS with a prevalence of 17.78%, which was completely reversible. CONCLUSION: Reduced-dose blinatumomab combined with hyper-CVAD chemotherapy as consolidation therapy seems to be feasible for adult B-ALL with acceptable side effects.