Efficacy and Safety Profile of Blinatumomab in Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia (R/R BCP-ALL) in Adults: A Systematic Review of Literature
Authors: Ibrahim Ahmed , Yousaf Muhammad Abdullah , Gull Nayab , Khalid Saba , Khalid Huma , Rehman Mohammad Ebad Ur , Alliende Anna Maria Akhtar , Shafqat Aiza Binte , Malik Mustafa Nadeem , Rafae Abdul 
Published: December 2024

Introduction:

Despite significant improvement in the complete remission (CR) rate of Precursor B-cell Acute Lymphoblastic Leukemia (Pre-B-ALL), adult patients with relapsed/refractory (R/R) type still suffer from poorer prognosis. However, novel therapies such as tyrosine kinase inhibitors, Bispecific T-cell Engagers and Chimeric Antigen Receptor T-cell therapy (CAR-T) have shown robust clinical outcomes in the recent past. Blinatumomab, a Bispecific T-cell Engagers antibody, has been showing promising efficacy in R/R BCP-ALL and has proven itself to be a bridge to Hematopoietic Stem Cell Transplant (HSCT) in this population. We aim to analyze and summarize the published literature on the efficacy and safety of blinatumomab in adult patients with R/R BCP-ALL.

Materials and Methods:

We performed an electronic search on PubMed, Cochrane Library, Web of Science, and Embase from inception to June 2024, following PRISMA guidelines using MeSH terms “Precursor B-Cell Lymphoblastic Leukemia-Lymphoma”, “refractory”, “relapsed”, AND “blinatumomab”. Eligible patients were ≥18 years old, had more than 5% blasts in their bone marrow, and had an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less. Both Ph-positive and Ph-negative B-cell precursor ALL patients, refractory to primary induction with combination chemotherapy, first relapse with the remission lasting less than twelve months, second or greater relapse, or relapse after hematopoietic stem-cell transplantation were included. Initially, 347 articles were identified and after a thorough screening, we included 13 articles containing data from 1387 patients. Phase II and phase III studies were included, in addition to data from the real world.

Results:

The median age of patients was 43.8 years. The primary endpoints were Complete Remission / Complete Remission with partial hematologic recovery (CR/CRh) and Minimal Residual Disease (MRD) response, which were 699/1387(52.6%) and 496/653(76%) respectively. The secondary endpoints of median Overall Survival (mOS) and median Relapse-Free Survival (mRFS) were also reported which were 11.08 months and 10.5 months respectively. HSCT was done in 331/708 (46.8%) patients. The safety profile was assessed based on the most frequently encountered ≥ Grade 3side effects, which were neurological events and cytokine release syndrome (CRS), in addition to hematological adverse effects of anemia, thrombocytopenia, and neutropenic fever.

Conclusion:

Immunotherapy drugs such as blinatumomab have led to a paradigm shift in ALL treatments. Data from the real world and research trials indicate that targeted immunotherapy with single-agent blinatumomab is an effective treatment for inducing remission in adults with relapsed or refractory BCP-ALL and has fewer side effects as compared to multi-drug chemotherapy regimens. Data emerging from ongoing clinical trials will help us better understand the role of immunotherapy and may even further change the treatment landscape of ALL.