Total body irradiation (TBI) has been a cornerstone in conditioning regimens prior to alloHSCT for acute lymphoblastic leukemia (ALL) patients. However, TBI is associated with long-term adverse effects, prompting the search for safer alternatives. Blinatumomab, a bispecific T-cell engager, offers a promising solution by targeting CD19-positive B cells, thus providing a novel approach to pre-transplant conditioning.
A phase III trial (NCT02393859) demonstrated that pediatric patients with high-risk, first-relapse B-ALL treated with blinatumomab before alloHSCT had significantly improved event-free and overall survival rates compared to those treated with standard chemotherapy. The study involved 90 evaluable patients, with 51 receiving blinatumomab and 39 receiving standard chemotherapy (HC3). The analysis showed that regardless of the conditioning regimen (TBI or chemoconditioning), patients treated with blinatumomab had better survival outcomes.
Key findings include:
- Improved Survival Rates: Patients treated with blinatumomab had a 2-year overall survival rate of 86.5% with TBI and 75.2% with chemoconditioning, compared to lower rates in the HC3 group.
- Reduced Relapse Rates: Only 29% of blinatumomab-treated patients relapsed post-transplant, versus 62% in the HC3 group.
- Minimal Residual Disease (MRD): Blinatumomab was associated with deeper MRD remission, which is predictive of better outcomes post-transplant.
This study underscores the potential of blinatumomab to enhance survival in pediatric high-risk B-ALL patients undergoing alloHSCT, offering a safer and more effective alternative to traditional chemotherapy. Further research is needed to explore the possibility of substituting TBI with chemoconditioning in patients achieving MRD negativity with blinatumomab.