The study team found that “an intensive pediatric ALL induction protocol can be delivered in an AYA [adolescent and young adult] cohort in a similar time frame to a pediatric population, suggesting that the inferior outcomes seen in AYA patients are more likely related to the biology of AYA ALL rather than intolerance of more intensive therapy,” said investigators led by Matthew Greenwood, MBBS, director of the stem cell transplant at the Royal North Shore Hospital, outside of Sydney
It’s been a long-standing question why intensive ALL regimens, which can be curative in children, don’t work as well in adolescents and young adults.
To see if tolerability and lack of adherence were issues, the investigators compared the treatment time lines of 82 AYA subjects with a median age of 22 years to the time lines of 608 children aged 1-17 years who were treated with the same intensive regimen (the ANZCHOG Study 8 protocol).
Induction/consolidation was equally deliverable in both populations. In the AYA group, 41.5% of subjects started the next phase of treatment – protocol M or high-risk (HR) therapy based on minimal residual disease (MRD) response to initial treatment – by day 94 versus 39.3% in the previous pediatric study (P = 0.77). The median time to protocol M/HR treatment was 96 days in AYAs and 98 days in children (P = .80).
About 52% of AYA subjects proceeded to HR therapy following induction/consolidation, versus just 10.7% in the pediatric study.
The investigators also found that a body mass index at or above 30 kg/m2 and the presence of MRD were both associated with worse disease-free and overall survival. “By addressing the factors predicting poorer outcomes from this study, we hope to significantly improve the outcomes for patients,” they said.
They noted that their work is the first to “report of the safety and efficacy of an MRD-stratified approach utilizing [Berlin-Frankfurt-Munich] HR therapy in an AYA cohort and show that this is a moderately efficacious strategy in patients who would otherwise be considered at high risk of relapse and death.”
Over a median follow-up of 44 months, estimated 3-year disease-free survival was 72.8% and estimated 3-year overall survival 74.9% in the AYA population.
The work was funded by the Australasian Leukaemia and Lymphoma Group. Several investigators had industry ties, including Dr. Greenwood, an adviser and/or researcher for Amgen, Pfizer, Servier, and Jazz.