An MRD-stratified pediatric protocol is as deliverable in adolescents and young adults as children with ALL

Abstract

Pediatric regimens have improved outcomes in adolescent and young adult (AYA) acute lymphoblastic leukemia (ALL). However, results remain inferior to children with ALL. The ALLG ALL06 study (anzctr.org.au/ACTRN12611000814976) was designed to assess whether a pediatric ALL regimen (ANZCHOG Study 8) could be administered to patients aged 15-39 years in a comparable time frame to children as assessed by the proportion of patients completing induction/consolidation and commencing the next phase of therapy - protocol M or high risk (HR) treatment - by day 94. Minimal residual disease (MRD) response stratified patients to HR treatment and transplantation. From 2012 to 2018, 86 patients were enrolled; 82 were eligible. Median age was 22 (range, 16-38) years. Induction/consolidation was equally deliverable in ALL06 as in Study 8. In ALL06, 41.5% (95%CI, 30.7-52.9) commenced protocol M or HR therapy by day 94 vs 39.3% in Study 8 (p=0.77). Median time to protocol M/HR treatment was 96 (IQR, 87.5-103) days in ALL06 vs 98 days in Study 8 (p=0.80). Induction mortality was 3.6%. With median follow up of 44 (1-96) months, estimated 3-year disease free survival (DFS) was 72.8% (95%CI, 62.8-82.7) and estimated 3-year overall survival (OS) was 74.9% (95%CI, 65.3-84.5%). End induction/consolidation MRD negativity rate was 58.6%. Body mass index (BMI) ≥30 and day 79 MRD positivity were associated with poorer DFS and OS. Pediatric therapy was safe and as deliverable in AYA patients as children with ALL. Intolerance of pediatric ALL induction/consolidation is not a major contributor to inferior outcomes in AYA ALL.