Outcomes of blinatumomab based therapy in children with relapsed, persistent, or refractory acute lymphoblastic leukemia: a multicenter study focusing on predictors of response and post-treatment immunoglobulin production

Abstract

The management of Refractory/Relapsed B-cell Acute Lymphoblastic Leukemia (R/R ALL) remains challenging. Incorporating blinatumomab in R/R ALL treatment has shown encouraging results. We describe the outcome and predictors of response in children receiving blinatumomab as a bridge to definitive therapy. Immunoglobulin (Ig) G and viral serology before and after therapy were evaluated. Thirty-three patients that failed standard first-line treatments due to relapsed ALL (n = 22), persistent minimal residual disease (MRD) (n = 8), or refractory disease (n = 3) received blinatumomab. Grade 2 toxicity occurred in 27.2% of patients. MRD remission (<0.01%) was achieved in 72.7% of patients. Pre-blinatumomab absolute lymphocyte count (ALC) and MRD/ALC ratio significantly associated with MRD-response. Patients with t(1;19) translocation had lower response rate, compared to all other cytogenetic categories (p = 0.013). One-year event-free survival (EFS) and overall survival (OS) were 69.2% and 79.7%, respectively. Analysis of OS and EFS showed pre-blinatumomab MRD level, ALC, MRD/ALC ratio, t(1;19), and post-blinatumomab MRD remission associated with survival. Following blinatumomab, 83% (15/18) of tested patients had low IgG levels. IgG seronegative status was observed in 83% (12/15) for varicella zoster, 35% (6/17) for herpes zoster, 18% (3/17) for cytomegalovirus, and 26% (5/17) for Epstein Barr virus. Blinatumomab produced encouraging results in children with R/R ALL and low disease burden bridging to definitive therapy. Incorporating baseline genetics and biomarkers may help identify subgroups likely to be responsive/resistant to therapy. Viral serological testing pre- and post-blinatumomab is recommended to optimize supportive and preemptive therapy.

Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2022.2049936 .

Keywords:

• Acute lymphoblastic leukemia
• absolute lymphocyte count
• blinatumomab
• immunoglobulin
• minimal residual disease

Acknowledgments

We thank the Saudi Arabian Pediatric Hematology Oncology Society (SaPHOS) for their support in this study and all team members who were involved in the care of our patients from departments of pediatric hematology/oncology, nursing, laboratory, pathology at all participating centers.

Disclosure statement

The authors report no conflict of interest in relation to this study.

Funding

The author(s) reported there is no funding associated with the work featured in this article.