The combination of alternating reduced-dose blinatumomab and hyper-CVAD as consolidation therapy in patients with newly-diagnosed adult B-cell acute lymphoblastic leukemia
Zixuan Li, Fang Liu, Chun Zhang, Jing He, WeiMing Li, Dairong Xie, Yuting Jiang, Ruofeng Jin, Tianran Gao, Mei Hong, Qiuling WuBackground
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.