The impact of early PEG-asparaginase discontinuation in young adults with ALL: a post hoc analysis of the CALGB 10403 study

Abstract

Asparaginase is a key component of pediatric-inspired regimens in young adults with acute lymphoblastic leukemia (ALL). Truncation of asparaginase therapy is linked to inferior outcomes in children with ALL. However, similar correlation in adults is lacking. Here, we studied the prevalence and risk factors associated with pegylated (PEG)-asparaginase discontinuation in young adults with ALL treated on the US intergroup CALGB 10403 study and examined the prognostic impact of early discontinuation (ED) (defined as <4 of 5 or 6 planned doses) on survival outcomes. The analysis included 176 patients who achieved complete remission and initiated the delayed intensification (DI) cycle. The median number of PEG-asparaginase doses administered before DI was 5 (range: 1-6), with 57 (32%) patients with early discontinuation. The ED patients were older (median=26 vs. 23 years; P=0.023). Survival was apparently lower for ED patients compared with those receiving =/> 4 doses, but this finding was not statistically significant (HR=1.82; 95%CI: 0.97-3.43, P=0.06), with corresponding 5-year OS rates of 66% and 80%, respectively. In patients with standard-risk ALL, the early discontinuation of PEG-asparaginase adversely influenced OS (HR=2.3; 95%CI: 1.02-5.22, P=0.04) with a trend toward inferior EFS (HR=1.84; 95%CI: 0.92-3.67, P=0.08). In contrast, there was no impact of early PEG-asparaginase discontinuation on OS (P=0.64) or EFS (P=0.32) in patients with high-risk disease based on the presence of high-risk cytogenetics, Ph-like genotype, and/or high WBC at presentation. In conclusion, early PEG-asparaginase discontinuation is common in young adults with ALL and may adversely impact survival of patients with standard-risk ALL.