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

Ibrahim Aldoss, Jun Yin, Anna Wall, Krzysztof Mrózek, Michaela Liedtke, David F. Claxton, Matthew C. Foster, Frederick R. Appelbaum, Harry P. Erba, Mark R. Litzow, Martin S. Tallman, Richard M. Stone, Richard A. Larson, Anjali S. Advani, Wendy Stock, Selina M. Luger

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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, a 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 Cancer and Leukemia Group B (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 ED. The ED patients were older (median, 26 vs 23 years; P = .023). Survival was apparently lower for ED patients compared with those receiving ≥4 doses, but this finding was not statistically significant (hazard ratio [HR], 1.82; 95% confidence interval [CI], 0.97-3.43; P = .06), with corresponding 5-year overall survival (OS) rates of 66% and 80%, respectively. In patients with standard-risk ALL, the ED of PEG-asparaginase adversely influenced OS (HR, 2.3; 95% CI, 1.02-5.22; P = .04) with a trend toward inferior event-free survival (EFS) (HR, 1.84; 95% CI, 0.92-3.67; P = .08). In contrast, there was no impact of early PEG-asparaginase discontinuation on OS (P = .64) or EFS (P = .32) in patients with high-risk disease based on the presence of high-risk cytogenetics, Ph-like genotype, and/or high white blood cell count 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.

Original languageEnglish (US)
Pages (from-to)196-204
Number of pages9
JournalBlood Advances
Volume7
Issue number2
DOIs
StatePublished - Jan 24 2023

All Science Journal Classification (ASJC) codes

  • Hematology

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