Children's Oncology Group AALL1331: Phase III Trial of Blinatumomab in Children, Adolescents, and Young Adults With Low-Risk B-Cell ALL in First Relapse

PURPOSE: Blinatumomab, a bispecific T-cell engager immunotherapy, is efficacious in relapsed/refractory B-cell ALL (B-ALL) and has a favorable toxicity profile. One aim of the Children's Oncology Group AALL1331 study was to compare survival of patients with low-risk (LR) first relapse of B-ALL treated with chemotherapy alone or chemotherapy plus blinatumomab. PATIENTS AND METHODS: After block 1 reinduction, patients age 1-30 years with LR first relapse of B-ALL were randomly assigned to block 2/block 3/two continuation chemotherapy cycles/maintenance (arm C) or block 2/two cycles of continuation chemotherapy intercalated with three blinatumomab blocks/maintenance (arm D). Patients with CNS leukemia received 18 Gy cranial radiation during maintenance and intensified intrathecal chemotherapy. The primary and secondary end points were disease-free survival (DFS) and overall survival (OS). RESULTS: = .53). Blinatumomab was well tolerated and patients had low adverse event rates. CONCLUSION: For children, adolescents, and young adults with B-ALL in LR first relapse, there was no statistically significant difference in DFS or OS between the blinatumomab and standard chemotherapy arms overall. However, blinatumomab significantly improved DFS and OS for the two thirds of patients with BM ± EM relapse, establishing a new standard of care for this population. By contrast, similar outcomes and poor DFS for both arms were observed in the one third of patients with IEM; new treatment approaches are needed for these patients (ClinicalTrials.gov identifier: NCT02101853).