The emerging importance and evolving understanding of clonal hematopoiesis in multiple myeloma.

Multiple myeloma (MM) is the second most common hematologic malignancy diagnosed in the United States. With a growing arsenal of novel therapies, patients are living longer and hence are at increased risk of secondary cancers such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). While MDS-associated cytogenetic abnormalities have been described in patients with a diagnosis of for decades, clonal hematopoiesis (CH) has been described only recently. CH has been shown to correlate with inferior survival in MM due to increased risk of disease progression in patients who are treated with high-dose melphalan without lenalidomide maintenance. When involving specific high-risk genes, multiple genes, or when present at high variant allelic frequencies, CH could also potentially elevate the risk of secondary MDS and/or AML, cardiovascular events, and venous thromboembolic events. Despite growing knowledge about CH in patients with MM, many questions remain unanswered. Further studies are needed to better understand the prognostic and therapeutic significance of CH in MM and its precursor conditions, as well as the effect of specific treatments on long-term outcome.