Safety and Efficacy of Blinatumomab and Auto-HSCT “Sandwich” Strategy As Consolidation Therapy for Ph Negative B Cell Acute Lymphoblastic Leukemia
Authors: Qian Chong-Sheng , Wang Zihao , Dai Lan , Yao Li , Yao Zhen , Zhou HaiXia , Xu Mingzhu , Gong Wenjie , Li Zheng , Dai Haiping , Sun Aining , Wu Depei , Xue Shengli 
Published: December 2024

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the principal consolidation therapy for B-cell acute lymphoblastic leukemia (B-ALL). However, complications such as graft-versus-host disease (GVHD) and infections contribute to increased treatment-related mortality (TRM), which in turn affects overall survival (OS). In comparison to allo-HSCT, autologous hematopoietic stem cell transplantation (auto-HSCT) exhibits a higher recurrence rate attributed to the loss of graft-versus-leukemia (GVL) effect and potential leukemia cell contamination, though it has a lower TRM. Recent studies indicated that patients who achieved deep remission before auto-HSCT could significantly reduce recurrence rates and achieve therapeutic effects comparable to allo-HSCT. The BLAST study demonstrated that 85 patients (78%) achieved minimal residual disease (MRD)-negative status after one cycle of blinatumomab treatment, suggesting that blinatumomab could effectively induce deep remission. Despite this, patients remain at a considerable risk of recurrence following HSCT, and the prognosis for those who relapse post-transplant is markedly poor, with a 5-year OS rate of only 10%. Thus, maintenance therapy post-transplant is crucial. Moreover, Gaballa et al reported that blinatumomab was effective in reducing the risk of recurrence in post-transplant patients.

Study design and methods: This multi-center, open-label, interventional study (NCT06507514) was designed to evaluate the safety and efficacy of combining blinatumomab with the auto-HSCT “Sandwich” strategy as consolidation therapy in adolescent, young adult (AYA), and adult patients with newly diagnosed CD19-positive B-ALL. Eligibility criteria included histologically confirmed CD19-positive B-ALL without extramedullary disease, an ECOG performance status score of 0-1, and no significant organ function abnormalities. Specific criteria of organ function included: cardiac ultrasound left ventricular ejection fraction ≥ 50%; creatinine ≤ 1.6 mg/dL; ALT and AST ≤ 3 times the normal range; total bilirubin ≤ 2.0 mg/dL; and pulmonary function with ≤ grade 1 dyspnea (CTCAE v5.0) and oxygen saturation &gt; 91% without supplemental oxygen. Forty patients will be enrolled in the study and will be treated with blinatumomab after standard induction and consolidation chemotherapy. Autologous stem cell mobilization and collection will be performed 1 week after blinatumomab. Following successful stem cell collection, auto-HSCT will be performed. After achieving reconstitution post-auto-HSCT (white blood cell [WBC] ≥ 3×109/L, platelet count [PLT] ≥ 50×109/L), patients will receive blinatumomab maintenance therapy for a total of four cycles. Patients will be followed up, with MRD monitored by flow cytometry and next-generation sequencing of IgH rearrangement. The primary outcome is the safety of the strategy and the secondary outcome is OS and leukemia-free survival.