Related Experiment Video
Updated: Feb 23, 2026
Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
Published on: June 6, 2025
A Phase II Study of Arginine Deiminase (ADI-PEG20) in Relapsed/Refractory or Poor-Risk Acute Myeloid Leukemia
Hui-Jen Tsai1,2,3, Shih Sheng Jiang1, Wen-Chun Hung1
1National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan.
Abstract:
Exogenous arginine is required for growth in some argininosuccinate synthetase (ASS)-deficient cancers. Arginine deiminase (ADI) inhibits growth in various ASS-deficient cancers by depleting arginine. The efficacy of pegylated ADI (ADI-PEG20) in relapsed/refractory/poor-risk acute myeloid leukemia (AML) was evaluated in 43 patients in a prospective, phase II trial (NCT01910012 (10/07/2013), https://clinicaltrials.gov/ct2/show/NCT01910012?term = ADI-PEG20&rank = 12 ). Despite almost all pre-treatment tumor samples showing ASS deficiency, the best response among 21 evaluable patients was complete response (CR) in 2 (9.5%) and stable disease in 7 (33.3%), yielding a disease control rate (DCR) of 42.9%. The response durations of the two patients with CR were 7.5 and 8.8 months. DCR was correlated with a median of 8 weeks of arginine depletion to ≤10 μM. Using whole transcriptome sequencing, we compared gene expression profiling of pre- and post-treatment bone marrow samples of the two responders and three non-responders. The expression levels of some markers for AML subtypes and c-MYC regulated genes were considered potential predictors of response to ADI-PEG20. These results suggest that ASS deficiency is a prerequisite but not a sufficient condition for response to ADI-PEG20 monotherapy in AML. Predictive biomarkers and mechanistic explorations will be critical for identifying appropriate patients for future AML trials of ADI-PEG20.
Insights
Arginine deiminase pegylated (ADI-PEG20) showed limited efficacy in acute myeloid leukemia (AML) despite ASS deficiency. Biomarkers are needed to predict which AML patients will respond to ADI-PEG20 therapy.
Area of Science:
- Oncology
- Cancer Metabolism
- Clinical Trials
Background:
- Argininosuccinate synthetase (ASS)-deficient cancers rely on exogenous arginine for growth.
- Arginine deiminase (ADI) depletes arginine, inhibiting growth in ASS-deficient cancers.
Purpose of the Study:
- To evaluate the efficacy of pegylated arginine deiminase (ADI-PEG20) in patients with relapsed/refractory/poor-risk acute myeloid leukemia (AML).
- To identify potential predictive biomarkers for response to ADI-PEG20 monotherapy in AML.
Main Methods:
- A prospective, phase II clinical trial was conducted with 43 AML patients.
- Whole transcriptome sequencing was used to compare gene expression profiles before and after treatment in responders and non-responders.
Main Results:
- The overall disease control rate (DCR) was 42.9% (2 complete responses, 7 stable diseases) among 21 evaluable patients.
- Complete responses lasted 7.5 and 8.8 months.
- DCR correlated with sustained arginine depletion (≤10 μM for 8 weeks).
Conclusions:
- Argininosuccinate synthetase (ASS) deficiency is necessary but not sufficient for response to ADI-PEG20 in AML.
- Predictive biomarkers and mechanistic studies are crucial for future ADI-PEG20 trials in AML.
More Related Videos
11:29HPLC-based Assay to Monitor Extracellular Nucleotide/Nucleoside Metabolism in Human Chronic Lymphocytic Leukemia Cells
Published on: July 20, 2016
09:49Isolation of Adipose Derived Regenerative Cells for the Treatment of Erectile Dysfunction Following Radical Prostatectomy
Published on: December 28, 2021