Impact of MRD Status and Depth of Response on Survival Outcomes in Blinatumomab-Treated ACUTE Lymphoblastic Leukemia: A Systemetic Review and Meta-Analysis
Authors: Siddique Rimsha , Jamil Abdur , Qureshi Zaheer , Altaf Faryal , Ahmad Mohsin 
Published: December 2024

INTRODUCTION
Acute lymphoblastic leukemia (ALL) is a common hematological malignancy that occurs due to blockage of B-lymphocyte maturation at an early stage of development and differentiation. This blockage of differentiation results in the increased circulation of clones of abnormal and immature B-cells that can involve either the peripheral blood, the bone marrow, or other extramedullary sites. ALL predominantly occurs in the pediatric populations, with most cases having a peak onset of between one and four years. ALL accounts for about 20% of all leukemias in adults, with about 60% diagnosed before age 20. Even with high remission rates, the long-term survival of ALL patients is still poor due to high rates of recurrence. It is, therefore, crucial that relapse be avoided or managed to improve patient outcomes. Blinotumomab, a bispecific antibody that binds to CD19 and CD3, was approved by the Food and Drug Administration to manage relapsed or refractory ALL (R/R ALL). Therefore, this review aims to determine the comparative efficacy of blinatumomab in managing (R/R ALL).
METHODS
Two independent reviewers systematically searched three electronic databases, PubMed, ScienceDirect, and CENTRAL, for all relevant articles published until July 2024. The articles found from the electronic databases were then included in the review if they met the following inclusion criteria: 1) Included patients with R/R ALL 2) Evaluated blinatumomab as one of the interventions 3) Reported the required outcomes. The statistical softwares RevMan 5.4 and Comprehensive Meta-Analysis version 3 were then used to pool the outcomes and present them using forest plots. The study's primary outcome was the overall survival (OS) and the disease-free survival (DFS). The secondary outcomes included the complete remission (CR) rates, the minimal residual disease (MRD) response rates, and the safety analysis.
RESULTS
A total of 1345 articles were found from the electronic search; however, only 22 articles met the inclusion criteria and were thus included in the review. A pooled analysis of the outcomes found that blinatumomab resulted in an improvement in both the OS (HR 0.65; 95% [0.51, 0.82] p = 0.0003) and the DFS (HR 0.57; 95% CI [0.41, 0.80] P = 0.001). Further analysis showed that the CR rates of ALL patients to blinotumomab was 55% (95% CI [CI 46.5%, 64.2%]) and the MRD response rate was 63.6% (95% CI [52.7%, 73.2%]). Lastly, the safety analysis indicated that the incidence of serious AEs was comparable in patients receiving blinotumomab and those receiving standard chemotherapy (OR 1.34; 95% CI [0.91, 1.97] p = 0.14). However, the incidence of hematologic AEs, i.e., anemia and thrombocytopenia, was significantly lower in the patients receiving blinatumomab than those receiving standard chemotherapy (OR 0.14; [0.08, 0.23] P &lt; 0.00001) and (OR 0.18; 95% CI [0.11, 0.30] P &lt; 0.00001). Similarly, hepatic toxicity was lower in patients receiving blinatumomab than those receiving standard chemotherapy (OR 0.46; 95% CI [0.30, 0.68] P = 0.0001).
DISCUSSION AND CONCLUSION
The results of this study indicate that blinatumomab is superior to standard chemotherapy in improving the OS and DFS of patients with R/R ALL. Furthermore, the CR and MRD response rates of blinatumomab in managing R/R ALL were 55% and 63.6%, respectively, indicating good efficacy and the ability to clear the MRD. Lastly, the safety analysis found that blinatumomab had a more favorable safety profile than standard chemotherapy. The superior effectiveness and the better safety profile thus make blinatumomab an effective alternative to managing R/R ALL.