ASH 2020 : Cellworks CBM Biosimulation Identifies Genomic Causes for Induction Failure in AML Patients and Suggests Alternative Therapies
myCare-021-02 study discovers patient-specific resistance mechanisms that can inform treatment planning and improve AML patient outcomes
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-021-02 clinical study, which found that personalized therapy response biosimulation using the Cellworks Omics Biology Model (CBM) can improve prognostication and identify new therapeutic options for Acute Myeloid Leukemia (AML) patients with resistant disease by incorporating patient-specific disease biomarkers.
Cellworks CBM relies on multi-omics inputs from malignant cells to predict and identify potential therapies tailored to the unique molecular mechanisms for each patient’s disease. The identification of patient-specific resistance mechanisms for AML patients provides a new therapeutic imperative founded on deep molecular diagnosis that can inform treatment planning, reduce patient risks, enhance disease outcomes and lower treatment costs.
Results from the myCare-021-02 clinical study will be featured as Oral and Poster Abstract #2820 on Monday, December 7, 2020 during the all-virtual 62nd American Society of Hematology (ASH) Annual Meeting and Exposition and published online at Blood®.
“AML is the leading cause of leukemia-associated death today, but a personalized therapy approach using Cellworks CBM can improve patient outcomes,” said Dr. Michael Castro, MD, oncologist specializing in molecular oncology, precision medicine and immunotherapy of cancer and principal investigator for the myCare-021-02 clinical study. “Response to remission induction therapy varies by biologic subtype and by the drugs used for induction, but responses are not predictable, even within specific biologic subgroups. The Cellworks CBM biosimulation platform provides a personalized medicine approach that targets patient-specific disease biomarkers and treatment resistance mechanisms.”
“Induction failure for AML is not rare, even in biological subgroups expected to have sensitive disease,” said Dr. Scott Howard, MD, MSc, Professor at University of Tennessee Health Science Center. “Cellworks CBM can identify causes of failure for standard induction regimes and suggest alternative therapies based on co-occurring genomic abnormalities in patients with resistant disease, despite their favorable biology.”
myCare-021-02 Clinical Study
The aim of this study was to predict the response to induction chemotherapy regimens in AML patients and identify predictive genomic signatures, pathways and personalized treatment options for refractory patients. For the study, 57 AML patients with known therapy response were selected from PubMed publications. The cohort was split into 3 groups with CBFB-MYH11 fusion (n=19), RUNX1-RUNX1T1 fusion (n=10) and CEBPα del (n=28). All data was anonymized, de-identified and exempt from IRB review. NCCN offers specific recommendations for AML patients with these mutations and they are associated with high rates of remission after induction therapy.
The available genomic data for each profile was processed using the Cellworks CBM biosimulation platform to generate an AML subtype-specific protein network map using published information from PubMed and other online resources permitting patient-specific biomarkers to be mapped to sensitivity and resistance pathways. Drugs selected from a digital drug library were simulated for each patient across the three cohorts. Benefit was assessed by measuring each drug’s effect on a cell growth score, a composite of proliferation, viability and apoptosis indices.
Results from the study found that of 57 patients with favorable-risk AML, 6 (11%) experienced induction failure. 1/19 patients harboring CBFB-MYH11 fusion failed to respond to induction therapy and Cellworks CBM identified co-occurring gene aberrations responsible for resistance in the patient with resistant disease, who harbored trisomy 6 with amplification of GSTA1, GSTA2, GSTA4, DEK, TFAP2A, NFYA and EHMT2 causing dysregulation of pathways involved in treatment failure. Cellworks CBM also identified 3 prospective therapies that target this patient’s specific biomarkers.
Similarly, 2/10 patients with RUNX1-RUNX1T1 fusion failed to respond to induction therapy. Cellworks CBM identified a loss of function mutation in EZH2 causing increased levels of HOXA5 and HOXA9 as key orchestrators of treatment failure. Furthermore, Cellworks CBM also identified three prospective therapies for this patient, targeting patient-specific resistance mechanisms.
In the CEBPα cohort, 3/28 patients did not respond to induction therapy. For one of these patients, Cellworks CBM identified a DNMT3A loss of function mutation and consequential gain in the levels of HOXA5 and HOXA9 as key orchestrators of treatment failure. Again, Cellworks CBM identified three novel therapies for this patient targeting patient-specific biomarkers.
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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