Commentary
Video
Author(s):
Sagar Lonial, MD, FACP, discusses the broad impact of the CoMMpass study on understanding the molecular underpinnings of multiple myeloma.
Sagar Lonial, MD, FACP, medical oncologist, chief medical officer, Winship Cancer Institute of Emory University; Anne and Bernard Gray Family Chair in Cancer, professor, chair, Department of Hematology and Medical Oncology, Emory University School of Medicine, discusses the broad impact of the Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profile (CoMMpass) study (NCT01454297) on understanding the molecular underpinnings of multiple myeloma.
CoMMpass has played an instrumental role in advancing the understanding of multiple myeloma at a molecular level, Lonial begins. This longitudinal, observational study enrolled 1,143 patients with newly diagnosed multiple myeloma. Tumor samples collected at baseline and at subsequent disease relapses were subjected to whole-genome, whole-exome, and RNA sequencing, allowing researchers to identify critical genetic alterations driving the disease. Through this, 8 distinct copy number subtypes and 12 expression subtypes of multiple myeloma were identified. Additionally, 25.5% of patients transitioned to a high-risk expression subtype during disease progression, emphasizing the evolving nature of the disease.
With over 300 abstracts and numerous published papers based on its data, CoMMpass has helped define key concepts, including the identification of "double-hit myeloma," a more aggressive form of the disease characterized by the presence of 2 or more high-risk mutations, he details.
Its influence also extends into drug development and target validation, Lonial adds. For instance, when new therapeutic targets are proposed in multiple myeloma, researchers often turn to CoMMpass data to assess the expression levels of these targets across various genomic subtypes of the disease, he expands. This validation process has become integral in advancing novel therapeutic strategies, Lonial says.
At many research centers, CoMMpass data are frequently used to understand the implications of specific genetic patterns and biomarker profiles in myeloma, Lonial continues. By offering insights into recurrent gain-of-function and loss-of-function events, the dataset provides a critical foundation for ongoing clinical research, he emphasizes. The study continues to shape the landscape of personalized medicine, as clinicians and researchers leverage this vast molecular database to tailor treatments based on a deeper understanding of the genetic underpinnings of multiple myeloma, Lonial concludes.