ASH 2020 : Cellworks Personalized Biosimulation Clinical Trial Predicted ATO and ATRA Therapy Response in APL Patients with 93% Accuracy
myCare-021-01 study found CBM has high accuracy for predicting therapy response in APL patients and can identify patient-specific biomarkers in non-responders
SOUTH SAN FRANCISCO, Calif., December 7, 2020 -- Cellworks Group, Inc., a world leader in Personalized Medicine in the key therapeutic areas of Oncology and Immunology, today announced results from the myCare-021-01 clinical trial, which found that the Cellworks Omics Biology Model (CBM) predicted response to Arsenic Trioxide (ATO) and All-trans-retinoic Acid (ATRA) in Acute Promyelocytic Leukemia (APL) patients harboring PML-RARA fusions with 93% accuracy. The study also demonstrated that Cellworks CBM can identify new mechanisms of resistance in APL patients and suggest alternative regimens for non-responders by targeting patient-specific disease biomarkers unique to each.
Results from the myCare-021-01 clinical study will be featured as Oral and Poster Abstract #2784 on Monday, December 7, 2020 during the all-virtual 62nd American Society of Hematology (ASH) Annual Meeting and Exposition and published online at Blood®.
The vast majority (99%) of APL patients have the PML-RARA fusion gene, which is the most critical event involved in the pathogenesis of APL. (Source: PMID: 32182684). The PML-RARA fusion confers a selective sensitivity to the targeted drugs, ATO and ATRA, with response rates over 90% (Source: PMID: 31635329 ). However, the mechanism of resistance in the minority of APL non-responders is not well understood. This study used the Cellworks Omics Biology Model (CBM) to predict response to the combination of ATO-ATRA in patients harboring the PML-RARA fusion and identify mechanisms of resistance.
“The ability of Cellworks CBM to accurately predict non-response to ATO and ATRA in APL patients with PML-RARA fusion up-front could prevent ineffective treatments, avoid unnecessary adverse events and reduce treatment costs,” said Dr. Scott Howard, MD, MSc, Professor at University of Tennessee Health Science Center. “In addition, we need an understanding of the mechanism of resistance in APL non-responders to prescribe more efficacious therapies and improve patient outcomes. In this study, the Cellworks CBM identified clinically relevant deletions to genes in patients who did not respond to ATO and ATRA and suggested alternative therapies. By taking this personalized approach to treating cancer patients, we can move the needle closer to the ideal 100% response rate.”
myCare-021-01 Clinical Study
In this study, outcomes of 30 APL patients treated with ATRA or ATRA plus ATO were compared with outcomes predicted by Cellworks CBM. Genomic data from 6 publications derived from whole exome sequencing (WES), targeted next-generation sequencing (NGS), copy number variation (CNV) and/or karyotype data were used. All data was anonymized, de-identified and exempt from IRB review.
The available genomic data for each profile was entered into the Cellworks CBM which generates a patient-specific disease protein network model using PubMed and other online resources. The CBM predicts the patient-specific biomarker and phenotype response of a personalized diseased cell to drug agents, radiation and cell signaling. Disease biomarkers that are unique to each patient were identified within the protein network models.
ATO and ATRA were simulated on all 30 patient cases. The treatment impact was assessed by quantitatively measuring the drug’s effect on a cell growth score which is a composite of the quantified values for cell proliferation, survival, and apoptosis, along with the simulated impact on each patient-specific disease biomarker score. Each patient-specific model was also digitally screened to identify response to ATO and ATRA.
Results of the study demonstrated that Cellworks CBM correctly predicted the response to ATO and ATRA in 28 of 30 cases. The overall prediction accuracy was 93% with a PPV of 100%, NPV of 60%, sensitivity of 93%, and specificity of 100%. In 2 of 30 patients who did not respond to ATO and ATRA, the CBM identified clinically relevant deletions to EZH2, KMT2E, and HIPK2 genes. All three genes are located on chromosome 7 and these non-responders had monosomy 7.
About Cellworks Group
Cellworks Group, Inc. is a world leader in Personalized Medicine in the key therapeutic areas of Oncology and Immunology. Using innovative multi-omics modeling, computational biosimulation and Artificial Intelligence heuristics, Cellworks predicts the most efficacious therapies for patients. The Cellworks unique biosimulation platform is a unified representation of biological knowledge curated from heterogeneous datasets and applied to finding cures. Backed by UnitedHealth Group, Sequoia Capital, Agilent and Artiman, Cellworks has the world’s strongest trans-disciplinary team of molecular biologists, cellular pathway modelers and software technologists working toward a common goal – attacking serious diseases to improve the lives of patients. The company is based in South San Francisco, California and has a research and development facility in Bangalore, India. For more information, visit www.cellworks.life and follow us on Twitter @cellworkslife.
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