A pediatric treatment-inspired approach may improve outcomes among adolescent and young adult (AYA) patients with Philadelphia-negative acute lymphoblastic leukemia (ALL), according to research published in the American Journal of Hematology.

Despite recent improvements in treatment, outcomes in AYA ALL remain inferior to those seen in pediatric patients. While there is some evidence that these differences are due to heterogenic disease biology between these patient populations, they may also be caused by differences in clinical strategies between hematologists specializing in pediatric vs adult care.

Recent evidence suggests that pediatric-inspired treatment regimens may yield improvements in event-free survival and overall survival (OS) in adults as old as 60 years. Patients aged up to 40 years may also be able to tolerate therapies similar to those used in pediatric populations.

For this study, researchers evaluated the safety and efficacy of a pediatric-inspired regimen among AYA patients with ALL (LAL1308; ClinicalTrials.gov Identifier, NCT01156883).


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The investigators used the ALL-2000 regimen, a minimal residual disease (MRD)-oriented combination that has yielded positive outcomes in pediatric patients. Outcomes were compared with those of a similar historical AYA population.

Overall, 76 patients, all of whom had Philadelphia-negative disease, were enrolled. At induction, 2 (2.7%) deaths were recorded; there were no deaths in the postconsolidation phase.

A complete response was noted in 92% of patients, with 48-month disease-free survival (DFS) and OS rates of 60.4% and 60.3%, respectively. Patients with T-cell lineage disease had a similar 48-month OS rate to that seen with B-cell lineage ALL (75.2% vs 54.2%, respectively; P =.27). In addition, DFS rates were better in patients with T-cell lineage disease compared with B-cell lineage disease (88.2% vs 50%, respectively; P =.005).

At the 2 MRD measurement timepoints, molecular MRD levels of less than 10-3 were associated with both improved DFS and OS. Compared with the historical AYA population the present regimen improved DFS and OS.

“In conclusion, in our experience, a pediatric-based and MRD-oriented treatment proved feasible and was associated with encouraging long-term results in AYA patients with [Philadelphia-negative] ALL,” the authors wrote. “MRD should be monitored in the management of AYA ALL patients and used in clinical trials, not only to risk stratify patients but also to determine which patients could be candidate to newer treatment strategies.”

Reference

Testi AM, Canichella M, Vitale A, et al. Adolescent and young adult acute lymphoblastic leukemia. final results of the phase II pediatric-like gimema LAL-1308 trial. Am J Hematol Published online December 7, 2020. doi:10.1002/ajh.26066