Dr Fonseca on the Role of Molecular Profiling in Multiple Myeloma Management

It sometimes feels like science fiction with all the detail we can get in our monitoring, but the advancements we’ve seen in treatment are best illustrated by the advancements we have in the diagnostic tools that allow us to confirm where patients are.

Rafael Fonseca, MD, a professor of medicine, chief innovation officer, a consultant in the Division of Hematology/Oncology in the Department of Internal Medicine, and director for Innovation and Transformational Relationships at Mayo Clinic, discussed the evolving role of molecular profiling in the diagnosis, risk stratification, and treatment selection for patients with multiple myeloma.

Molecular profiling has been central to both the biologic understanding of multiple myeloma and its management in the clinic, Fonseca said. For many years, the field has followed a paradigm of classifying patients into high-risk and standard-risk groups, and this distinction has shaped differing treatment recommendations and approaches across those populations, he explained.

That risk stratification was traditionally performed with fluorescence in situ hybridization (FISH), a technique Fonseca noted he was closely involved in developing. FISH remains a routine part of clinical practice. However, multiple publications have shown that implementing next-generation sequencing (NGS) yields improved results, according to Fonseca. Although NGS is associated with more technical challenges, it should now be accessible to most large cancer centers and academic institutions, and it can refine the findings that have traditionally been assessed with FISH, he said.

Fonseca added that many centers now have genetic testing panels available, which are particularly informative for patients who are going to have re-exposure to an agent such as a BCMA-targeting therapy, which is a consideration relevant to CAR T-cell therapy and bispecific antibody decision-making. In that setting, whole genome sequencing can be used to look for mutations or deletions in the relevant gene that might alter treatment decisions, he explained.

Beyond diagnosis and risk assessment, genomics is also used to determine minimal residual disease status, which is assessed through NGS, Fonseca noted. Ultimately, Fonseca concluded that the advances seen in treatment are best illustrated by the parallel advances in diagnosis and the diagnostic tools that allow confirmation of where patients stand in their disease.