AALL1731 trial

Dr Sumit Gupta, a paediatric oncologist and assistant professor at the Hospital for Sick Children and the University of Toronto, Canada, presented the main findings of the AALL1731 study, of which he is the co-author.

The AALL1731 trial investigated treatment strategies for paediatric patients with standard-risk B-cell ALL. Standard risk was defined as patients younger than 10 years of age with presenting white blood cell counts below 50,000/µL. Within this cohort, participants were further stratified into two subgroups: those at average risk and those at higher risk of relapse. The trial randomised patients to receive either the standard chemotherapy regimen or the same chemotherapy regimen combined with two non-sequential cycles of blinatumomab.

An interim efficacy analysis of the trial was conducted in June, overseen by an independent Data Safety and Monitoring Committee. Based on the interim findings, the committee recommended terminating the trial early and releasing the results due to the superior outcomes observed in the blinatumomab-augmented chemotherapy group. Among patients at average risk of relapse, three-year DFS was 90% with chemotherapy alone, compared to 97.5% with the addition of blinatumomab. In the higher-risk subgroup, three-year DFS was 85% with chemotherapy alone and improved to 94% with the combination therapy. The addition of blinatumomab effectively elevated outcomes in both subgroups to levels previously seen only in the most favourable risk profiles. 

Moreover, blinatumomab demonstrated an acceptable safety profile. Known side effects, including cytokine release syndrome and neurotoxicity, were infrequent in this study. While an increased incidence of bloodstream infections and line-associated infections was noted, these events primarily occurred during subsequent chemotherapy cycles rather than during blinatumomab administration. Importantly, severe infections (grade 4 or 5) were not more frequent in the blinatumomab group compared to chemotherapy alone.

In conclusion, blinatumomab being added to chemotherapy represents a new standard of care for the majority of children with B-cell ALL and it really has changed standard treatment for this population around the world according to these results.