Efficacy and Safety of Blinatumomab As Maintenance Therapy in Patients with High-Risk B-Lineage Acute Lymphoblastic Leukemia Post Allogeneic Hematopoietic Cell Transplantation

Introduction: Allogeneic hematopoietic cell transplantation (allo-HCT) is a promising treatment for patients with high-risk B-lineage acute lymphoblastic leukemia (B-ALL). To reduce the risk of relapse, we explored the role of blinatumomab as maintenance therapy post allo-HCT in patients with high-risk B-ALL. This study aimed to investigate the efficacy and safety of blinatumomab therapy post allo-HCT in patients with B-ALL.

Methods: This is a prospective, single-arm phase II study. The efficacy of 4 cycles of blinatumomab administered every 3 months post allo-HCT was investigated. Eligible patients received blinatumomab at a dose of 8.75 µg/day from day 1-4, 17.5 µg/day on days 5 and 6, and 28 µg/day from day 7-16. Patients administered with bevacizumab prior allo-HCT, received blinatumomab at a dose of 17.5 µg/day on days 1 and 2, 28 µg/day on day 3-12. The primary endpoints were the 3-year cumulative recurrence rate (CIR) and drug related toxicity. Secondary endpoints included overall survival (OS), progression free survival (RFS), non-relapse mortality (NRM), incidence of acute and chronic graft-versus-host disease (GVHD). Inclusion criteria included patients: (1) aged ≥14 years (2) Undergone allo-HCT, including HLA-matched sibling, haploidentical donor, and unrelated donor transplantations (3) High risk acute B-ALL (such as Ph+B-ALL, Ph like B-ALL, high white blood cell counts at onset, and no remission after 2 cycles of chemotherapy) (4) Complete remission with minimal residual disease (MRD) negativity including absolute neutrophil and platelet counts of ≥1.0×109/L and ≥50×109/L, respectively, for >1 week (5) ≤ grade 3 acute GVHD or moderate to severe chronic GVHD within 30 days prior to enrollment (6) Signed the informed consent form. Exclusion criteria included: (1) Patients with hematological or MRD recurrence (2) Presence of severe active infections (3) Significant abnormalities in routine laboratory tests (4) ECOG physical fitness status score ≥3 (5) Expected survival period < 3 months. OS and non-relapse mortality were calculated from the date of allo-HCT to the last recorded vital sign. PFS was calculated from the date of allo-HCT to the date of disease progression or death. OS and PFS were estimated by Kaplan-Meier method. The cumulative incidences of relapse, NRM, and GVHD were evaluated by competing risks method. The competing risk for relapse was death, for NRM was relapse, and for GVHD were relapse and death. Group differences in OS and PFS were evaluated by stratified log-rank test, while cumulative incidences were assessed by stratified Gray’s test.

Results：Eleven patients were enrolled to date and received at least 1 cycle of blinatumomab (range:1-4) during the first-year post allo-HCT. Of the patients, 73% were male with a median age of 34 (16-62) years. The median number of days from allo-HCT to cycle 1 of blinatumomab was 78 days (range: 44-105). Decrease of immunoglobulin A and G was the most common side effects, occurred in 10 patients. During medication, 3 patients developed fever, 2 patients developed headaches and 1 patient developed mild pulmonary infection, which improved after anti-infectious treatment. Hematologic cytopenia, including leukopenia was reported in 5 patients, neutropenia in 2 patients with acute grade 1 GVHD in 1 patient. The median time of follow-up from diagnosis to allo-HCT was 2.5 months (range: 3-67). Only 1 patient reported molecular biology recurrence, while the remaining patients remained in durable remission. No cases of non-relapse mortality were reported.

Conclusion: Blinatumomab maintenance therapy post allo-HCT has shown initial feasibility and efficacy for B-ALL and is well tolerated. Future studies with a large number of patients are required to confirm its efficacy.