Dr Lonial on Findings from the CoMMpass Trial in Multiple Myeloma

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EP: 1.Dr Lonial on Findings from the CoMMpass Trial in Multiple Myeloma

EP: 2.Dr Lonial on Characterizing Multiple Myeloma Subtypes in the CoMMpass Study

EP: 3.CoMMpass Data Continue to Shape Understanding of Genomic Diversity in Multiple Myeloma

EP: 4.Myeloma Molecular Profiling Reveals Unique Copy Number and Expression Subtypes

EP: 5.Dr Lonial on the Impact of the CoMMpass Study on Personalized Medicine in 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 findings from the observational Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profile (CoMMpass) study (NCT01454297), which evaluated subtypes of multiple myeloma and identified high-risk genetic markers in patients with this disease.

When CoMMpass began, the expectation was to identify a dominant mutation in myeloma, similar to what is seen inchronic myeloid leukemia or Waldenström macroglobulinemia, where a single mutation can be targeted to effectively control the disease, Lonial begins. However, after sequencing the first few hundred patients, it became evident that the genetic mutation pattern in myeloma was like what is observed in many solid tumors, he reports. Common mutations, such as those in RAS and p53, were frequently found in the patients with multiple myeloma, Lonial states.

Interestingly, mutations typically associated with other cancers were also identified, such as IDH mutations often seen in leukemia and BRAF mutations commonly found in melanoma, lung cancer, and other malignancies, he continues. Although these mutations were only present in a small percentage of patients, they represent potential targets that can be treated using therapies developed for other solid tumors, such as MEK, RAS, and BRAF inhibitors, according to Lonial. Despite these findings, no single dominant mutation or clone was present in many patients with myeloma, Lonial explains.

This finding likely reflects the fact that multiple myeloma is a multifocal disease, with several factors potentially driving the initial clonal plasma cell formation, he expands. As a result, the disease does not lend itself to a straightforward, single-target therapeutic approach, according to Lonial. Instead, multiple mechanisms contribute to myeloma’s development, making it more complex to treat than originally anticipated, Lonial emphasizes. The study highlights the need for a diverse treatment strategy rather than a singular, mutation-driven target, he concludes.