Overview of blinatumomab for pediatric B-ALL

The ALL Hub was pleased to speak to David Teachey, Children’s Hospital of Philadelphia, Philadelphia, US. Teachey discussed blinatumomab for the treatment of pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL).

Teachey provides an overview of several key clinical trials that assessed the safety and efficacy of blinatumomab in pediatric and young adult patients with B-ALL. He then discusses some ongoing questions regarding the use of blinatumomab as a first-line therapy for these patients.

Key learnings

• Blinatumomab is becoming the standard of care treatment for most pediatric and young adult patients with B-ALL in the US.
• Blinatumomab, a type of immunotherapy referred to as a bispecific T-cell engager, links CD3+ T cells to CD19+ B cell blasts, allowing the T cells to attack and kill the B cell blasts.
• Blinatumomab was recently approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult and pediatric patients aged ≥1 month who have CD19-positive, Philadelphia chromosome-negative B-ALL in the consolidation phase of multiphase chemotherapy.¹
• A randomized phase III trial (NCT02393859) assessed consolidation chemotherapy plus one cycle of blinatumomab vs consolidation chemotherapy alone in pediatric patients aged >28 days and <18 years with high-risk first-relapse B-ALL in complete remission at randomization.²
  • This trial included 108 patients from 47 centers across Europe.
  • The trial was stopped early for efficacy; the incidence of events (relapse, death, second malignancy, or failure to achieve complete remission) in the blinatumomab plus chemotherapy vs chemotherapy alone groups was 31% vs 57% (hazard ratio [HR], 0.33; 95% confidence interval [CI], 0.18–0.61; p < 0.001).
• The randomized phase III AALL1331 trial (NCT02101853) evaluated consolidation with two cycles of blinatumomab vs two cycles of consolidation chemotherapy in patients aged 1–30 years with first-relapse B-ALL.³
  • Patients were risk stratified into higher-risk and lower-risk groups.
  • The higher-risk portion of this trial included 208 patients from 155 centers in the US, Canada, Australia, and New Zealand.³
  • This trial was stopped early for efficacy and low toxicity; among higher-risk patients,  the 2-year disease-free survival (DFS) for the blinatumomab vs chemotherapy group was 54.4% vs 39.0% (HR, 0.70; 95% CI, 0.47–1.03; p = 0.03).³
  • The lower-risk portion of this trial included 255 patients, and patients received maintenance chemotherapy rather than proceeding to transplantation.⁴
  • In the blinatumomab vs chemotherapy groups, the 4-year DFS was 61.2% vs 49.5% (p = 0.089).⁴
  • The benefit of blinatumomab was primarily observed in patients with bone marrow ± extramedullary disease, while patients with isolated extramedullary relapse had poor outcomes in both treatment groups.⁴
• The randomized phase III ECOG-ACRIN E1910 trial (NCT02003222) assessed the addition of four cycles of blinatumomab to consolidation chemotherapy vs four cycles of consolidation chemotherapy in newly diagnosed patients aged 30–70 years with BCR::ABL1-negative B-ALL who had measurable residual disease negative remission after induction.⁵
  • Interim results from this trial included 224 patients; after a median follow-up of 43 months, in the blinatumomab vs chemotherapy groups the 3-year overall survival was 85% vs 68% (HR, 0.41; 95% CI, 0.23–0.73; p = 0.002) and the 3-year relapse-free survival was 80% vs 64% (HR, 0.53; 95% CI, 0.32–0.87).
• The randomized phase III AALL1713 trial (NCT03914625) assessed the addition of two cycles of blinatumomab to chemotherapy vs chemotherapy alone in pediatric patients with National Cancer Institute (NCI) standard-risk B-ALL who had an average or high risk of relapse.⁶
  • This trial included 1,440 patients.
  • The trial was terminated early due to efficacy; in the blinatumomab vs chemotherapy groups, the overall 3-year DFS was 96.0% vs 87.9% (p < 0.001).
  • Among patients with an average relapse risk, the 3-year DFS was 97.5% vs 90.2%.
  • Among patients with a high relapse risk, the 3-year DFS was 94.1% vs 84.8%.
• A phase II trial (EudraCT number, 2016-004674-17) assessed blinatumomab in newly diagnosed, infant patients with KMT2A-rearranged ALL.⁷
  • This trial included 30 patients who received the Interfant-06 trial chemotherapy regimen with the addition of one post-induction cycle of blinatumomab.
  • The 2-year DFS was 81.6% vs an expected 49.4%.
• Several studies are investigating blinatumomab in combination with tyrosine kinase inhibitors with a chemotherapy-light or chemotherapy-free backbone with promising initial results.
• Questions remain around the patients who are most likely to benefit from blinatumomab, the optimal number and length of cycles, the impact of a reduction in chemotherapy on central nervous system relapses, and the impact of giving blinatumomab in the first-line on blinatumomab responses and relapse.
• The introduction of immunotherapies into first-line treatment may reduce the amount of chemotherapy used going forward, potentially to chemotherapy-free treatments in the future.
  

This educational resource is independently supported by Amgen. All content is developed by SES in collaboration with an expert steering committee; funders are allowed no influence on the content of this resource.