Impact of TP53 mutations on outcomes following blinatumomab treatment in adults with B-cell ALL

The bispecific CD19 × CD3 T-cell engager blinatumomab has been approved for the treatment of relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL), ALL with persistent measurable residual disease (MRD), and as consolidation therapy for Philadelphia chromosome-negative B-cell ALL. Treatment failure, however, is common in the R/R setting, and can present with antigen loss and extramedullary disease progression.

Aldoss et al. published findings in Blood Advances from an analysis of the impact of patient and disease factors on outcomes after treatment with blinatumomab, in adults with B-cell ALL (N = 267). Patients received blinatumomab for R/R ALL (n = 150), for MRD (n = 88), upfront as induction (n = 10), or as consolidation in an MRD-negative state (n = 19). Response was defined as complete remission (CR) or CR with incomplete hematologic recovery. 

Key learnings 

The CR/CRi rate in patients with R/R ALL was 59%. Only high disease burden prior to blinatumomab (p < 0.01) and active EMD (p < 0.01) were associated with inferior CR/CRi outcomes.

Among patients who responded to blinatumomab (n = 169), 47% experienced relapse (CD19–, 13%; CD19+, 32%; unknown, 2%). TP53m was associated with increased risk of CD19– relapse (p < 0.01), thus is a potential predictor of CD19– relapse following blinatumomab.

Allo-HSCT consolidation following blinatumomab treatment was associated with a lower risk of CD19– relapse (p < 0.01) and EMD relapse (p < 0.01) compared with no allo-HSCT consolidation.

The analysis identified TP53m as a predictor of inferior outcomes following blinatumomab treatment for ALL, which may help guide treatment decisions in TP53m ALL.