Predicting and preventing clonal evolution in multiple myeloma

Irene Ghobrial

Irene Ghobrial of Dana-Farber Cancer Institute, Boston, MA discusses clonal evolution of multiple myeloma (MM) and the steps that could be taken to treat or even prevent it at the 2017 annual meeting of the European Society for Blood and Marrow Transplantation. MM is driven by clonal evolution from MGUS (monoclonal gammopathy of undetermined significance) to smoldering MM to overt MM. However, the drivers and mutations behind this clonal progression are currently unknown. It becomes increasingly complex due to the different types of MM, hyperdiploid and non-hyperdiploid, which cascade into secondary events. Not every patient undergoes disease progression, so it is important to develop and employ procedures that identify patients more susceptible to it than others. Blood biopsies can be carried out on MM patients and used to predict the presence of clonal hydrogenates and minimal residual disease which in turn can aid in determining patients that require closer monitoring than others. It is not just important to identify mutations but it is also crucial to understand how these mutations are regulated, and it has been recently demonstrated that the tumor microenvironment can have a profound effect on further clonal evolution. Research in this subject area can allow for advances in immunotherapy leading to better treatment and prevention options, especially in patients with smoldering MM.

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