Clinical Summary: 

• Design/Population: This randomized trial evaluated replacement of 2 intensive chemotherapy blocks with 2 cycles of blinatumomab in newly diagnosed pediatric patients with high-risk B-cell acute lymphoblastic leukemia.
• Key Outcomes: Blinatumomab improved event-free survival, reduced relapse rates, enhanced minimal residual disease clearance, and decreased treatment-related toxicity compared with intensive chemotherapy.
• Clinical Relevance: These findings support incorporation of blinatumomab into frontline treatment and demonstrate that immunotherapy can successfully replace highly toxic chemotherapy components.

Results from a phase 2 study demonstrated that replacing 2 intensive chemotherapy courses with blinatumomab, a bispecific T-cell engager,  improved outcomes and reduced treatment-related toxicity in newly diagnosed pediatric patients with high-risk B-cell acute lymphoblastic leukemia (B-ALL).

These results were presented by Martin Schrappe, MD, PhD, University Medical Center Schleswig-Holstein, Kiel, Germany, at the 2026 European Hematology Association (EHA) Congress in Stockholm, Sweden. 

In this study, following induction, consolidation, and 1 intensive chemotherapy course, 709 patients were randomized to receive either 2 cycles of blinatumomab plus intrathecal methotrexate (n = 358) or 2 intensive chemotherapy blocks (n = 351). The primary end point was 4-year event-free survival (EFS). Secondary end points included treatment-related toxicity, mortality, and minimal residual disease (MRD) response.

At a median follow-up of 2.9 years, 4-year EFS was 83% in the blinatumomab arm and 70.3% in the chemotherapy arm (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.35 to 0.73; P = .0002). The cumulative incidence of relapse was 11.8% and 21.4%, respectively. Isolated central nervous system relapse was reported in 0.3% of patients in the blinatumomab arm and 2.5% of patients in the chemotherapy arm.

Among patients who had detectable MRD before randomization, MRD burden decreased in 76.9% of patients in the blinatumomab arm 45.8% of patients in the chemotherapy arm (P < .0001).

Clinically relevant infectious adverse reactions were reported in 22.8% of patients in the blinatumomab arm and 69.4% of patients in the chemotherapy arm (P < .001). Severe mucositis or stomatitis requiring hospitalization occurred in 0.3% and 10% of patients, respectively. Neurologic adverse reactions were reported in 11.7% of patients in the blinatumomab arm and 2.9% of patients in the chemotherapy arm (P < .001). Grade ≥2 cytokine release syndrome was reported in 1.1% of patients in the blinatumomab arm.  

Life-threatening adverse events were reported in 1 patient in the blinatumomab arm and 16 patients in the chemotherapy arm. Among patients undergoing allogeneic stem cell transplantation, non-relapse mortality was 2.5% and 16%, respectively. 

“For the first time, in newly diagnosed ALL, highly toxic chemotherapy elements have successfully been replaced by blinatumomab demonstrating a safer but also superior anti-leukemia efficacy of immunotherapy in prognostically unfavorable pediatric B-ALL,” concluded Dr Schrappe. 

Source: 

Schrappe M, Locatelli F, Valsecchi MG, et al. Replacement of high dose combination chemotherapy with blinatumomab in newly diagnosed pediatric high-risk B-cell ALL improves efficacy and safety in the randomized phase 2 AIEOP-BFM All 2017 trial. Presented at EHA Congress. June 11 - June 14, 2026. Stockholm, Sweden. Abstract EHA-3803.