Efficacy and safety of blinatumomab as frontline treatment for infant acute lymphoblastic leukemia

Abstract Background Infant acute lymphoblastic leukemia (IALL) is highly aggressive with poor prognosis, representing a key focus and challenge in pediatric leukemia research globally. Multiple center studies have demonstrated the favorable efficacy of blinatumomab in adult and pediatric ALL. We report the efficacy and safety of frontline blinatumomab for infant ALL patients in our center. Methods We retrospectively analyzed 11 IALL patients treated with blinatumomab as frontline treatment at Beijing Children's Hospital, Capital Medical University, between March 2023 and March 2025. Inclusion criteria included: (1) age at diagnosis < 12 months, (2) B-cell precursor acute lymphoblastic leukemia, and (3) never received any IALL-related treatment. All patients were risk-stratified according to the Chinese Children's Leukemia Group 2018-ALL (CCLG-2018-ALL) protocol, and blinatumomab was administered at induction treatment, consolidation treatment, and post-consolidation intensification stages. All patients received cycles of blinatumomab therapy ranging from half a cycle (14 days) to 3 cycles: 3 patients completed 3 cycles, 4 patients received 2 cycles, and 2 patients were treated for half a cycle. Among the high-risk patients (n=8), 5 pts received concomitant venetoclax (BCL2 inhibitor) during their first blinatumomab cycle. MRD was assessed by MFC monitoring leukemia-associated aberrant immunophenotypes (sensitivity 1×10⁻⁴), PCR detecting fusion gene (sensitivity 1×10⁻5), and next-generation sequencing (NGS) of immunoglobulin genes (sensitivity 1×10⁻⁶). Adverse events were assessed according to CTCAE 5.0. Results This study included 11 patients with a median age of 8.5 months (range: 1.3-11.5 months), of whom 7 (63.6%) were female. According to risk stratification, 3 cases (27.3%) were classified as intermediate-risk (IR) and 8 (72.7%) as high-risk (HR). All 8 HR patients harbored KMT2A rearrangements, including 5 patients with MLL::AF4 fusion, 2 patients with MLL::ENL, and 1 patient with MLL::AF9. Of the 3 IR patients, 1 patient carried PAX5::PROSER1 fusion. Median WBC at diagnosis 31.06×109/L (1.42, 346.21); 1pts with CNS3, 4pts with CNS2 at diagnosis. All patients achieved bone marrow complete remission (CR) after 15 days of induction therapy, and 2 patients achieved minimal residual disease (MRD) negativity. Among the 8 patients who initiated blinatumomab immunotherapy during induction (after induction day 15, replacing the subsequent 2-week phase of induction), 1 patient had negative bone marrow MRD on day 15 of induction; the remaining 7 patients achieved MRD negativity after 14 days of blinatumomab treatment. All pts maintained CR until the end of follow-up, with the longest event-free survival (EFS) of 20 months in the youngest patient. Of the 3 patients who started blinatumomab after induction, 1 patient had persistent MRD negativity since day 15 of induction with an EFS of 23 months; the other 2 patients, whose MRD remained positive after induction, both achieved MRD negativity after blinatumomab treatment. One of these 2 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) following consolidation therapy, while the other patient experienced relapse during consolidation with an EFS of 12 months, after which allo-HSCT was performed. Adverse events during the first blinatumomab treatment cycle included respiratory infections (4 patients), diarrhea (3 patients, grade 2), elevated transaminases (1 patient grade 2, 1 patient grade 3), and 1 patient with PICC-associated bloodstream infection. Treatment-related cytokine release syndrome (CRS) of grade 1 occurred in 4 pts, with no severe CRS events or immune effector cell-associated neurotoxicity syndrome (ICANS) observed. Conclusions This retrospective study suggests that blinatumomab combined with chemotherapy can greatly eliminate leukemia cells and achieve favorable remission in infant ALL. Early administration of blinatumomab may lead to early negativity of MRD, and the adverse reactions are manageable. It is expected that new immunotherapeutic agents will change the treatment predicament of childhood ALL, especially infant ALL. However, large-scale clinical data and longer follow-up are still needed for verification.