Clinical Impact of Drug Adherence of Tyrosine Kinase Inhibitors in Children with Ph-Positive Acute Lymphoblastic Leukemia.

Abstract

PURPOSE:

This study aimed to explore the impact of ABL1-tyrosine kinase inhibitors (TKIs) adherence on the survival of chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) children and clarify the potential predictors of patients' prognosis from TKIs intake practices.

Materials and Methods:

Ninety newly diagnosed Ph+ ALL patients who received TKIs were enrolled. We collected the baseline characteristics and adverse events in all children; moreover, TKIs adherence was measured by an eight-item Morisky medication adherence scale (MMAS-8). Progression-free survival (PFS) and overall survival (OS) analysis were performed, and risk factors for PFS and OS were evaluated.

RESULTS:

Among all patients, 69 cases were regarded as adherers, while 21 were non-adherers. The median duration of TKIs interruption was significantly prolonged in the non-adherence group than in the adherence group (13 [0-101] vs. 56 [11-128], p < 0.001). Additionally, dose reduction occurred in 55.2% of non-adherers versus 23.0% of adherers (p=0.002). The PFS and OS in adherers were significantly higher versus non-adherers (p=0.020 and p=0.039). MMAS-8 score was an independent risk factor for PFS (p=0.010) and OS (p=0.031). Among non-adherers, the median OS was only 23.1% (4.2%-42%) in patients aged ≤ 10 years versus 54.4% (38.8%-70%) in adolescents. Most of the patients who experienced TKIs non-adherence suffered pancytopenia.

CONCLUSION:

TKIs adherence during treatment significantly influenced the survival of pediatric Ph+ ALL patients, and non-adherers with age ≤ 10 years were more vulnerable to TKIs disruption. The cumulative TKIs dose should be especially emphasized to patients with age ≤ 10 years, which may result in an inferior achievement of relevant treatment milestones.

• Authors: Jun-Xia Wang, Miao-Miao Yang, Li-Peng Liu, Hui-Min Zhang, Meng-Chuan Wang, Yu-Wen Chen, Xiao-Ying Zang, Fang Hu
• Journal: Cancer research and treatment (Cancer Res Treat) Vol. 55 Issue 3 Pg. 1023-1030 (Jul 2023) ISSN: 2005-9256 [Electronic] Korea (South)
• PMID: 36758956 (Publication Type: Journal Article)

Chemical References

• Protein Kinase Inhibitors
• Tyrosine Protein Kinase Inhibitors

Topics

• Adolescent
• Humans
• Child
• Protein Kinase Inhibitors (adverse effects)
• Tyrosine Protein Kinase Inhibitors
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (therapy)
• Prognosis
• Medication Adherence