How should patients with ALL be selected for blinatumomab treatment?

The ALL Hub was pleased to speak with André Baruchel, Robert-Debré University Hospital, Paris, FR. We asked, How should patients with acute lymphoblastic leukemia (ALL) be selected for blinatumomab treatment?  

In this interview, Baruchel discusses how patients with B-cell ALL (B-ALL) should be selected for blinatumomab treatment. He highlights several considerations, including tumor burden, measurable residual disease (MRD) response, CD19 expression, and patient fitness. He also explains the role of blinatumomab as a chemotherapy-sparing treatment and as a bridge to allogeneic hematopoietic stem cell transplantation (allo-HSCT). 

Key points 

• Blinatumomab is a bispecific CD19-directed CD3 T-cell engager currently approved by: 
  • The U.S. Food and Drug Administration for adult and pediatric patients with CD19+ Philadelphia chromosome-negative B-ALL during consolidation, CD-19+ B-ALL in first or second complete remission with MRD ≥0.1%, and relapsed/refractory CD19+ B-ALL.¹ 
  • The European Commission for adults with CD19+ Philadelphia chromosome-negative relapsed/refractory B-ALL or CD19+ Philadelphia chromosome-positive B-ALL in first or second complete remission with MRD ≥0.1%, and for pediatric patients with CD19+ Philadelphia chromosome-positive B-ALL which is refractory or in relapse after receiving ≥2 prior therapies or in relapse after receiving prior allo-HSCT.² 
• Expert recommendations support the inclusion of blinatumomab in first-line treatment strategies for the majority of patients with B-ALL, either in combination with or as a replacement for conventional chemotherapy.³ 
• A high tumor burden is associated with an increased risk of cytokine release syndrome (CRS) and neurologic toxicity; therefore, patients with a lower tumor burden, or those who can undergo tumor-lowering strategies, are likely to have improved outcomes with blinatumomab.⁴ 
• Favorable responses to blinatumomab are particularly noted in patients persistent or recurrent MRD after chemotherapy.^1,5 
  • Blinatumomab may also have a role in MRD-negative complete remission, with the ECOG-ACRIN E1910 study (NCT02003222) demonstrating higher 3-year overall survival with blinatumomab plus chemotherapy vs chemotherapy alone (85% vs 68%; hazard ratio, 0.41; 95% confidence interval, 0.23–0.73; p = 0.003).⁶ 
• Blinatumomab requires CD19+ disease; prior CD19-directed therapy can lead to reduced (CD19-dim) or absent CD19 expression, which is associated with poorer outcomes with subsequent CD19-directed therapies.⁷  
• Blinatumomab is less myelosuppressive than conventional chemotherapy and therefore provides a chemotherapy-sparing option for patients who have experienced significant chemotherapy-related toxicity.⁸ 
• As a medical history of neurologic signs and symptoms is associated with an increased risk of neurological events with blinatumomab, treatment risk vs benefit should be carefully considered in these patients.^1,2 Little is currently known about the use of blinatumomab in patients with active uncontrolled infection; all patients who receive blinatumomab should be monitored for signs and symptoms of infection.² 
• Blinatumomab can also be used to bridge patients to allo-HSCT or to provide disease control in relapsed/refractory ALL. ^1,3 
• In pediatric B-ALL, emerging evidence is helping to further define the role of blinatumomab in first-line treatment, including its potential to replace or reduce components of chemotherapy.^9,10