A Systematic Review on Efficacy and Safety Profile of Blinatumomab in Relapsed or Refractory B-Cell Precursor Acute Lymphoblastic Leukemia (R/R BCP-ALL) in Children and Young Adults

Introduction:

Chemotherapy for relapsed or refractory B-cell precursor Acute Lymphoblastic Leukemia (R/R BCP-ALL) is associated with a high-grade toxicity profile and in a few cases subsequent relapse in children and adolescents. However, the bispecific T cell-binding antibody blinatumomab (target CD19/CD3) has been used successfully for the treatment of R/R BCP-ALL in pediatric populations with a favorable adverse effect profile and early bridging to Hematopoietic Stem Cell Transplant (HSCT). In this study, we report a systematic review of published literature on the efficacy and toxicity profile of blinatumomab in children, including data from the real world.

Materials and Methods:

Following PRISMA guidelines, an electronic search was performed on PubMed, Embase, Cochrane Library, Web of Science, and Clinicaltrials.gov, from inception to June 2024. Eligible patients were older than 28 days and younger than 18 years with an Eastern Cooperative Oncology Group score of 2 or less. Children included in this study were required to have B-cell precursor ALL, either refractory to induction or salvage chemotherapy treatments, or with relapsed disease after chemo and/ or hematopoietic stem cell transplantation. Initially, 347 articles were identified, and we finalized 12 studies with single-agent use of blinatumomab for inclusion in our review after a thorough screening. MeSH terms were “Precursor B-Cell Lymphoblastic Leukemia-Lymphoma,” “refractory”, “relapsed”, “safety”, “efficacy”, AND “blinatumomab”.

Results:

According to the reported data, the median age (mAge) was 8.6 years. Number of patients achieving Complete Remission or Complete Remission with incomplete hematologic recovery (CR/CRh) was 322 out of 555 (58%). The pooled Minimal Residual Disease (MRD) response was observed in patients 66.5% and 70.8% of patients were able to undergo HSCT. Blinatumomab treatment showed a median Overall Survival (mOS) of 10.35 months and a median Relapse-Free Survival (mRFS) of 12.7 months. The most frequently reported greater than grade 2 adverse events (AEs) were neutropenic fever (NF), cytokine release syndrome (CRS), and neurological events like headache, altered sensorium encephalopathy, etc.

Conclusion:

The current data reinforces that single-agent immunotherapy with blinatumomab is more effective in treating R/R BCP-ALL children facilitating early transplantation, and is safer, compared to standard-of-care chemotherapy. The toxicity with blinatumomab is majorly limited to cytokine release syndrome and neurologic events but is controllable and low in number. Prospective studies with longer follow-ups and bigger sample sizes, need to be conducted, to help us better understand blinatumomab.

No relevant conflicts of interest to declare.