Dr Lonial on Characterizing Multiple Myeloma Subtypes in the CoMMpass Study

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 characterization of multiple myeloma subtypes identified through the Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profile (CoMMpass) study (NCT01454297), highlighting data on the transition of patients to high-risk categories at disease progression. 

The CoMMpass study analyzed subtypes of multiple myeloma, identifying significant high-risk genetic markers in patients. This study highlighted that genetic subgroups identified in previous research using gene expression profiling (GEP), remain valid when evaluated through mutation patterns, Lonial notes. For instance, the study confirmed the existence of subgroups such as those associated with the t(4;14) and t(11;14) translocations, which also divided into two distinct groups similar to findings in earlier GEP analyses, he states. Additionally, a hyperdiploid group reemerged, further reinforcing the relevance of these genetic classifications in multiple myeloma, Lonial adds.

A critical finding from this study involves the changes that occur over the course of the disease, particularly after multiple relapses, Lonial continues. As patients progress, a significant shift towards activation of the proliferation pathway occurs, indicating a loss of the indolent plasma cell phenotype, he explains. This shift leads to an increased proliferative state of the cancer cells, with a corresponding decrease in plasma cell markers that are commonly targeted by current therapies. Treatments such as proteasome inhibitors, immunomodulatory drugs, anti-CD38 monoclonal antibodies, and B-cell maturation antigen therapies primarily target plasma cell markers. As the disease becomes more aggressive and loses these markers, the effectiveness of these therapies diminishes, Lonial says.

This finding is particularly important as it suggests that as multiple myeloma evolves, treatment strategies will need to adapt, Lonial emphasizes. Future therapeutic approaches may need to focus less on targeting plasma cell markers and more on addressing the proliferative nature of the disease, specifically in relapsed or refractory settings, he notes. This evolving understanding of myeloma’s biology underscores the need for ongoing research to develop therapies that can tackle these more aggressive forms of the disease, Lonial concludes.