A collaboration between GNS Healthcare and the Multiple Myeloma Research Foundation (MMRF) resulted in the discovery of a biomarker called CHEK1 that detects which myeloma patients might benefit from a stem cell transplant.
The finding was recently revealed at the 59th American Society of Hematology (ASH) Annual Meeting in a presentation titled, “Multiple Myeloma Drivers of High Risk and Response to Stem Cell Transplantation Identified by Causal Machine Learning: Out-of-Cohort and Experimental Validation.”
Understanding the molecular basis of cancer is a critical step toward developing the most effective treatments for each patient. The development of targeted therapies and being able to identify patients who respond to such treatments through the use of biomarkers has revolutionized cancer care.
Despite extensive research and clinical advances in myeloma, personalized treatment for this type of cancer is still out of reach.
MMRF and GNS Healthcare combined efforts to identify new myeloma therapies and develop tailored treatments. In the study, myeloma patient information was analyzed through GNS’ patented causal learning and simulation platform called REFS (Reverse Engineering & Forward Simulation).
Patient data came from the MMRF CoMMpass trial (NCT01454297), the largest and most comprehensive study providing new genomic insights and accelerating personalized medicine in multiple myeloma. This longitudinal study enrolled 1,150 newly diagnosed patients with active myeloma from 90 sites worldwide.
The new collaboration aims to assess the relationship between patients’ genomic profiles and clinical outcomes. This will provide a better understanding of disease processes, patient responses to treatments, and patient relapse.
To achieve that, REFS created a network model from 645 patients of the MMRF CoMMpass trial database. This artificial intelligence (AI) platform goes beyond correlations and defines causal mechanisms between variables, bringing us closer to personalized medicine.
REFS was able to identify the CHEK1 gene as a biomarker of patient response to stem cell treatment. While no benefit from stem cell transplants was seen in patients with high CHEK1 levels, those with low levels of this gene remained alive and disease-free for an extra 22 months after receiving the transplant.
CHEK1 is known to be involved in the activation of DNA repair pathways in response to DNA damage. High levels of CHEK1 have been associated with both solid tumors and blood cancers, increased resistance to chemotherapy or radiation treatment, and reduced survival. Accordingly, suppression of CHEK1 has been shown to increase sensitivity to chemo-radiotherapy in multiple tumor models.
This discovery supports a more effective treatment of patients, helping doctors decide whether a patient will benefit from a costly, invasive treatment such as a stem cell transplant.
“The ability to better match multiple myeloma patients with stem cell therapy is a crucial finding in the fight against this terrible cancer,” Colin Hill, chairman, CEO, and co-founder of GNS Healthcare, said in a press release.
“Our platform, using the MMRF’s patient data, reverse engineered models of the patient mechanisms and simulated stem cell treatment patient by patient. Our discovery revealed who will and who will not respond to stem cell transplantation,” he added.
“We believe this work can help answer the questions that are most important to multiple myeloma patients and their families and will drive towards more precision-based approaches for all patients,” said Paul Giusti, president and CEO of the MMRF.
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