Impact of Philadelphia chromosome-like alterations on efficacy and safety of blinatumomab in adults with relapsed/refractory acute lymphoblastic leukemia: a post hoc analysis from the phase 3 TOWER study.

Philadelphia chromosome (Ph)-like acute lymphoblastic leukemia (ALL) is a high-risk subgroup of precursor B-cell (BCP) ALL. In the phase 3 TOWER trial (NCT02013167), blinatumomab demonstrated superior overall survival (OS) than standard of care chemotherapy (SOC) in adults with relapsed/refractory BCP ALL. The impact of Ph-like alterations on the efficacy and safety of blinatumomab and SOC is evaluated in this post hoc analysis of the TOWER trial. Among patients randomized 2:1 (blinatumomab:SOC) in the TOWER trial (n=405), 142 RNA samples were analyzed for gene fusions and mutations reported in Ph-like ALL. Fifteen (11%) patients had Ph-like ALL; 9 (60%) were treated with blinatumomab and 6 (40%) with SOC. Remission rates <12 weeks after blinatumomab treatment initiation were similar in patients with or without Ph-like ALL (complete remission [CR], 33% vs 36%; CR with partial hematologic recovery, 11% vs 10%). No patients with Ph-like ALL receiving SOC achieved remission. In patients with Ph-like ALL, the median OS was longer following blinatumomab than SOC (7.9 vs 4.0 months, HR, 0.39 [95% CI, 0.04-3.78]). A total of 44% of patients with Ph-like ALL receiving blinatumomab underwent allogeneic stem cell transplantation. Toxicity profile was similar in both treatment groups. The efficacy and safety of blinatumomab appeared similar in patients with or without Ph-like ALL, thereby potentially negating the effect of Ph-like alterations. The superior outcomes of blinatumomab compared with SOC in patients with Ph-like ALL were consistent with that in the TOWER study. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

RCT Entities:   Population Interventions Outcomes