Pediatric Patients with Acute Lymphoblastic Leukemia Treated with Blinatumomab in a Real-World Study

Abstract

Introduction Pediatric B-cell acute lymphoblastic leukemia (B-ALL) involves chromosomal abnormalities and genetic alterations at an early stage of differentiation of lymphoid precursor cells. Most children (~around 80%) with B-ALL can achieve long-term survival with conventional chemotherapy but a sizable number of patients relapse or do not attain complete remission. Blinatumomab is a bispecific T-cell engager antibody designed to redirect CD3+ T cells to bind to CD19+ target cells. Although blinatumomab has been approved for the treatment of relapsed or refractory B-ALL, it has shown efficacy in newly diagnosed B-ALL also. Here, we studied the effect of blinatumomab in newly diagnosed B-ALL (including infantile B-ALL) and post-induction therapy measurable residual disease (MRD) positive B-ALL in a real-world study. Methods Pediatric patients with B-ALL including newly diagnosed infants (infantile type) or with MRD positivity during the induction remission phase, were enrolled. The patients received a 7-day pre-treatment VCP regimen consisting of intravenous infusions of cyclophosphamide 800 mg/m 2 on day 1, vindesine 3 mg/m 2 on day 1, prednisone 1-2 mg/kg on days 1 to 7 (VCP regimen), followed by 28 days of treatment with blinatumomab at 5µg/m 2/day on the first 1 to 7 days and 15 µg/m 2/day on the next 8 to 28 days. Four patients with economic burden received blinatumomab for 14 days: 5µg/m 2/day for days 1 to 4 and 15 µg/m 2/day from day 5 to 14, after pre-treatment with the VCP regimen. Bone marrow assessment of MRD was done on days 14 and 28. Results Between July 2022 and July 2023, 24 pediatric patients received VCP-blinatumomab. Among them, 11 (45.8%) patients had high-risk disease, and 5 (20.8%) had standard risk. The median age of the cohort was 8.5 years. Among the cohort, there was 1 patient with infantile B-ALL and 1 patient with Philadelphia chromosome-positive (Ph+)-ALL; besides 3 patients were TEL-AML positive, 3 patients were CRLF2 positive, 1 patient was E2A-PBX1 positive, 1 patient was SSBP2-CSF1R positive, and 1 patient was EVI1 positive. Blinatumomab was administered to 5 patients in the induction remission period, and for 2 patients, blinatumomab was administered in consolidation after inotuzumab ozogamicin (INO). While 18 patients were treated with blinatumomab for 28 days, 6 patients were treated with blinatumomab for 14 days. Four patients opted for a 14-day regimen due to financial reasons and 2 patients were transplanted with hematopoietic stem cell transplantation after 14 days of treatment with blinatumomab. All the treated patients achieved MRD negativity (100%). There were no ≥ grade 3 treatment-related toxicity and no deaths reported. Conclusion Our study results showed that a 100% MRD negativity rate was achieved in children with B-ALL after treatment with the blinatumomab consolidation following the chemotherapy and no significant safety concerns were observed. Blinatumomab consolidation therapy was also effective in patients pretreated with INO. Blinatumomab consolidation after induction therapy could be a new and effective strategy for the treatment of patients with newly diagnosed B-ALL.