Efficacy and Safety of Blinatumomab Versus Chemotherapy in Treating First-Relapse B-ALL: A Meta-Analysis of Randomized Controlled Trials
Authors: Qandil Hamzah , Khan Salman , Khan Malik W.Z. , Ali Aizaz , Hussain Amna , Khamis Zaid , Yetiskul Ekrem , Niazi Muhammad , Alsughayer Anas , Mian Aban Masaud , Tahir Ammara , Araji Ghada , Ali Shandana , Afif Sarah 
Published: December 2024

Introduction: B-cell Acute Lymphoblastic Leukemia (B-ALL) is a common hematologic malignancy, in which B lymphocyte precursors become arrested in an early phase of differentiation, leading to an excess of immature cells invading the bone marrow, peripheral blood, and other extra-medullary sites. Despite treatment advances, relapse rates remain high: around 10% in children and 50% in adults. Standard relapse treatments include chemotherapy, radiotherapy, and potentially hematopoietic stem cell transplantation (HSCT). Blinatumomab, a bispecific antibody targeting CD3 and CD19, has shown improved survival rates in relapsed B-ALL through randomized controlled trials (RCTs). This meta-analysis evaluates the efficacy and safety of Blinatumomab compared to chemotherapy in first-relapse B-ALL patients.

Methods: An extensive electronic search was conducted across PubMed, Embase, Cochrane Database of Systematic Reviews, ClinicalTrials.gov, the American Society of Clinical Oncology (ASCO), and the American Society of Hematology (ASH) databases up to July 25, 2024. The search utilized relevant MeSH terms and keywords, including “Blinatumomab” and “Precursor Cell Lymphoblastic Leukemia-Lymphoma”. Our inclusion criteria focused on randomized controlled trials (RCTs) comparing the efficacy and safety of blinatumomab versus chemotherapy in first-relapse B-ALL. Primary efficacy outcomes included disease-free survival (DFS) and overall survival (OS). Secondary outcomes assessed were safety profiles, including adverse events such as anemia, decreased platelet count, decreased white blood cell count, hypokalemia, and febrile neutropenia. Dichotomous variables were analyzed using the Mantel-Haenszel method with a random effects model. Heterogeneity was assessed using the I² statistic. Statistical analyses were conducted using Review Manager (RevMan, Version 5.4).

Results: Record screening of 1,203 articles initially included 3 RCTs for analysis, all of which met our eligibility criteria. A total of 286 B-ALL patients were included across three RCTs with 55.17% of the participants being male. Blinatumomab significantly improved DFS (HR 0.59, 95% CI 0.38-0.91, P=0.02, I²=63%) and OS (HR 0.59, 95% CI 0.41-0.83, P=0.003, I²=0%) compared to chemotherapy. Subgroup analysis showed superior DFS for Blinatumomab in bone marrow (BM) relapse (HR 0.44, 95% CI 0.28-0.69, P=0.0003, I²=1%), while it was comparable in isolated extramedullary (IEM) relapse (HR 0.94, 95% CI 0.53-1.67, P=0.83, I²=10%). The analysis of overall survival (OS) showed that Blinatumomab was significantly superior over chemotherapy, with (HR 0.59, 95% CI 0.41, 0.83, P=0.003, I2=0%).

Blinatumomab had a slightly higher risk of any adverse events (RR 1.05, 95% CI 1.01-1.09, P=0.01, I²=0%) but reduced grade ≥3 adverse events such as hypokalemia (RR 0.27, 95% CI 0.15-0.48, P&lt;0.00001, I²=0%), anemia (RR 0.31, 95% CI 0.23-0.41, P&lt;0.00001, I²=0%), febrile neutropenia (RR 0.15, 95% CI 0.08-0.27, P&lt;0.00001, I²=31%), leukopenia (RR 0.70, 95% CI 0.52-0.94, P=0.02, I²=44%), and thrombocytopenia (RR 0.24, 95% CI 0.11-0.49, P&lt;0.0001, I²=44%).

Conclusion: Blinatumomab significantly improves DFS and OS in first-relapse B-ALL patients compared to chemotherapy, with a favorable safety profile. Its efficacy and reduced occurrence of severe adverse events make it a superior therapeutic option for treating first-relapse B-ALL.