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.

Disclosures

No relevant conflicts of interest to declare.

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2024
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