A Comparison of Outcomes Between Adolescents and Young Adults (AYA) and Children with Acute Promyelocytic Leukemia (APL): North American Intergroup Study CALGB 9710 (Alliance)
Authors: Kutny Matthew A. , Geyer Susan , Laumann Kristina M , Gregory John , Willman Cheryl L. , Stock Wendy , Larson Richard A. , Powell Bayard L. , Feusner James H. 
Published: October 2019

Abstract
Purpose: Recent studies have demonstrated differential outcomes for adolescents and young adults (AYAs) vs. children treated for acute myeloid leukemia. Here we analyze outcomes by age group for APL patients treated on the North American Intergroup Study C9710.
Methods: Patient characteristics and outcomes were compared between children (<15 yr, n=55) vs. AYAs (15-31 yr, n=42). To control for differences in treatment center, only young adults registered at Children’s Oncology Group (COG) treatment sites were included. Treatment included induction with daunorubicin, cytarabine and ATRA. All patients (pts) received two consolidation cycles with daunorubicin and ATRA and maintenance for one year with ATRA +/- mercaptopurine and methotrexate. Pts ≥15 yr were randomized to an additional two cycles of arsenic trioxide (ATO). Sub-group analysis was also performed to exclude pts ≥15 yr who received ATO and thus compare only patients <15 yr vs. ≥15 yr who had not received ATO.
Results: Children and AYAs had similar characteristics of gender, race/ethnicity, Sanz risk grouping and M3v histology. Among all pts enrolled at COG sites on the study, complete response (CR) rates were similar (<15yr =85% vs. ≥15yr =81%, P=0.59). AYAs had improved 5 yr disease-free survival (DFS) from time of CR compared to younger pts (<15 yr =47% vs. ≥15 yr =70%, log rank P=0.05), and there was a trend toward difference in 5 yr event-free survival (EFS) (<15 yr =46% vs. ≥15 yr =63%, log rank P=0.13). Overall survival (OS) at 5 years was not significantly different (<15 yr =82% vs. ≥15 yr =75%, log rank P=0.47). Twenty-three of 42 pts ≥15 yr received ATO consolidation cycles, which may have contributed to their improved DFS and EFS. Thus, we analyzed outcomes by removing from the analysis patients ≥15 yr who received ATO consolidation cycles, and compared pts <15 yr who did not receive ATO (n=55) to pts ≥15 yr who were randomized to no ATO (n=19). CR rates were again similar (<15 yr =85% vs. ≥15 yr no ATO =84%, P=1.0). There was no significant difference in other outcomes including 5-yr DFS from time of CR (<15 yr =47% vs. ≥15 yr no ATO =63%, log rank P=0.31), 5-yr EFS (<15 yr =46% vs. ≥15 yr no ATO=53%, log rank P=0.89), or 5-yr OS (<15 yr =82% vs. ≥15 yr no ATO=79%, log rank P=0.78).
Conclusions: The C9710 study demonstrated improved EFS, DFS and OS among adult patients receiving ATO consolidation compared to those who did not receive ATO (Powell et al., Blood, 2010). The current analysis of results for AYAs versus younger pediatric pts showed improved DFS among the whole AYA cohort (of which 55% received ATO consolidation) compared to pts <15 yr (of which 0% received ATO). When the analysis was restricted to AYA pts not receiving ATO, however, the results of this intergroup APL trial showed similar CR, DFS, EFS and OS for AYAs and younger pts. Thus, unlike other subtypes of AML, APL appears to have a consistent response across the pediatric and AYA age groups. The most recent COG clinical trial in APL is now evaluating whether pediatric patients can also benefit from ATO consolidation.

Disclosures
Off Label Use: Daunorubicin- labeled for use in AML for adults and for pediatric ALL (not pediatric AML) Arsenic Trioxide- labeled for use in relapsed/refractory APL (not de novo APL) Mercaptopurine and Methotrexate- labeled for use in pediatric ALL (not APL).