Conceptual illustration of multiple myeloma in the bone marrow. (iStock.com)
Lead author of the pivotal research is Sagar Lonial, MD, FACP, chief medical officer at Winship Cancer Institute of Emory University.
Data from the Multiple Myeloma Research Foundation (MMRF) landmark CoMMpass study, published today in Nature Genetics, offers a comprehensive understanding of multiple myeloma’s progression from a treatable condition to a high-risk state by providing unprecedented insights into the genetic diversity and subtypes of the disease.
The CoMMpass study, one of the most extensive genomic investigations ever conducted on multiple myeloma, analyzed data from 1,143 newly diagnosed, previously untreated patients. The findings reveal critical genetic markers that can better predict disease progression and identify patients at risk of transitioning to more aggressive forms of the disease. Lead author of the pivotal research is Sagar Lonial, MD, FACP, chief medical officer at Winship Cancer Institute of Emory University and professor and chair of the Department of Hematology and Medical Oncology at the Emory University School of Medicine.
“Despite efforts to understand the molecular basis of the disease, predicting patient outcomes and identifying high-risk patients has remained a challenge,” says Lonial. “The breadth of the MMRF CoMMpass study enabled us to identify distinct copy number and expression subtypes of myeloma, as well as both recurrent and rare molecular events that occur at frequencies that would not be detected in smaller patient cohorts. We can now see the rate at which patients transition to the high-risk subtype at progression.”
The study defines the frequency of gene alterations in myeloma from diagnosis to relapse and offers the most thorough understanding of the genetic diversity and subtypes of myeloma to date. Findings reveal new insights about the complexity of newly diagnosed multiple myeloma as well as disease behavior at relapse from treatment.
Multiple myeloma is the second most common blood cancer in the US with an estimated 35,750 new cases and 12,590 deaths this year. New targeted agents and therapies have resulted in better outcomes, but most multiple myeloma patients eventually relapse.
The new publication details a molecular analysis and median four-year follow up of the complete baseline cohort of the MMRF’s CoMMpass study, a prospective, longitudinal observational clinical study. The collaborative research, led by authors from MMRF, Emory University and TGEN, comprehensively describe the subtypes of myeloma, including rich detail of the high-risk subtype that is less sensitive to therapy. The study also details molecular events at relapse and quantifies how the tumors of some standard risk patients convert to high risk at relapse, elevating the importance of understanding this subtype to develop more effective treatment plans.
“This study refines our understanding of how frequently patients transition from a more treatable type to high-risk disease, highlighting the need to focus on high-risk subtypes and disrupt this progression,” said George Mulligan, PhD, chief scientific officer at the MMRF. “As a research organization dedicated to the urgent pursuit of more effective treatments for every myeloma patient, we are gratified that our team’s efforts have shed new light on this challenging disease and that our CoMMpass study continues to accelerate both science and solutions.”
MMRF’s CoMMpass data represents the largest single sequencing study of multiple myeloma patients undertaken based on the number of enrolled patients and the total number of sequencing assays performed. For over a decade, CoMMpass data has been analyzed by more than 200 researchers worldwide, making it one of the most highly published datasets in myeloma.
More about the study
To understand the diverse array and frequency of genetic events that can contribute to the development or progression of cancer, the MMRF consortium of researchers conducted a molecular analysis of seven different data formats extracted from whole genome, whole exome and RNA sequencing data. Among several new insights, this enabled differentiation between partial and complete loss of function of the TP53 gene, a key driver of progression in multiple myeloma and many other cancers.
Findings clearly defined the primary molecular features associated with different subtypes of multiple myeloma and identified high-risk patients at both diagnosis and progression. These molecular analyses, using whole genome and RNA sequencing were found to be better predictors of disease behavior than current staging systems.
“These data underscore the durable value of the collaboration that MMRF facilitates and sustains,” said Jonathan Keats, PhD, assistant professor and director of bioinformatics, Translational Genomics Research Institute (TGEN). “As one of the only public datasets with regular updates, CoMMpass will continue to define mechanisms of resistance, and novel changes associated with disease progression and open up new therapeutic opportunities.”