Screening in Multiple Myeloma and Its Precursors: Are We There Yet?

Abstract

Background Multiple myeloma (MM) is a hematological malignancy that develops over years from the asymptomatic precursors, monoclonal gammopathy of undetermined significance, and smoldering multiple myeloma. Recent evidence shows that by initiating treatment at an asymptomatic stage, outcomes in MM can be significantly improved. However, a vast majority of MM patients are diagnosed after the development of symptomatic end-organ damage and cannot reap the benefits of early treatment. The precursors of MM are easily detected by serum protein electrophoresis and free light chain assay of the serum, raising the question of whether population-based screening could detect MM at an asymptomatic stage and significantly expand the availability of early treatment in MM. Screening is a hallmark of care in many malignancies, and there are accepted criteria for when screening is appropriate. Content Here we review the available relevant evidence for the introduction of screening and discuss whether screening for MM and its precursors fulfills these criteria. We also highlight gaps in our current knowledge, most notably a lack of data on the benefits and harms of screening and the lack of a defined target population. There are ongoing studies that may fill these critical gaps in the literature, but their results are still pending. Summary Screening could lead to a paradigm shift in the care of patients with MM, but critical scientific questions need to be answered before screening of healthy individuals can be recommended. In short, we should not screen for MM and its precursors—yet.

Multiple myeloma incidence and mortality trends in the United States, 1999–2020

“…During this period, MM mortality rates have fallen to 18% while five-year overall survival rates have increased to nearly 54%, driven by novel therapies introduced over the past two decades amidst other advancements in cancer care 7 , 8 . Nevertheless, MM remains a significant cause of mortality and morbidity, leading to 2.1 million disability-adjusted life-years lost since 2016 9 , 10 . Significant disparities exist, with incidence rates among non-Hispanic Black Americans being more than two-fold higher compared to their non-Hispanic White counterparts, as well as disproportionately higher five-year mortality rates 7 .…”

“…Thus, early detection and intervention of MGUS and SMM are crucial to slow progression to MM, improve life expectancy, and mitigate potential end-organ damage 11 . Prior research suggests that patients previously diagnosed with MGUS have a lower likelihood of presenting with end-organ disease at MM diagnosis, correlating with a 13–15% increase in their overall survival, possibly attributed to their access to earlier treatment and support services 10 , 12 , 13 . Current consensus guidelines recommend continuous monitoring of individuals diagnosed with MGUS to identify progression to MM, yet the asymptomatic nature of MGUS and SMM poses challenges for early clinical intervention 14 .…”