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, 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.

• Authors: 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
• Journal: Blood advances (Blood Adv) Vol. 7 Issue 2 Pg. 196-204 (01 24 2023) ISSN: 2473-9537 [Electronic] United States
• PMID: 36269846 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

Chemical References

• pegaspargase
• Asparaginase
• Polyethylene Glycols

Topics

• Child
• Humans
• Young Adult
• Asparaginase (adverse effects)
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (drug therapy)
• Polyethylene Glycols (adverse effects)
• Remission Induction