Recent Advances in the Management of Smoldering Multiple Myeloma

Abstract

There is remarkable progress in the treatment of multiple myeloma (MM) with significant improvement in survival in the past 10 years. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) can evolve into symptomatic multiple myeloma (sy-MM) with organ involvement. SMM has associated with a much higher progression to MM compared to MGUS. In 2014, International Myeloma Working Group (IMWG) reclassified ultra-high-risk smoldering myeloma patients with bone marrow plasma cells > 60% or serum-free light chain ratio (FLCr) > 100 or > 1 focal bone lesion on the magnetic resonance imaging as MM. SMM is a heterogeneous disorder with probability for progression to myeloma up to 50% in the first 5 years. Several risk models and clinical features have been identified to stratify the risk of progression to MM. Thanks to advances in our understanding of the genomic profile of MM, there are several ongoing clinical trials, and genomic studies are being done to assess the risk of progression to MM and early intervention. There is still no standard criterion regarding when to start therapy. This review discusses identifying SMM patients who are at high risk of progression to sy-MM and recent development of new and early treatment strategies and ongoing clinical trials for these high-risk SMM patients.

Accurate classification of plasma cell dyscrasias is achieved by combining artificial intelligence and flow cytometry

“…We found an 84% abnormal PC cut‐off to be able to differentiate between MGUS and MM, than the 95% threshold described previously 13,21 . This finding must be explained by the use of the Gini index to classify MGUS‐SMM‐MM 18 .…”

“…The loss of CD38 is known between SMM and MM transition 21 and is meant to be extended to the MGUS–SMM–MM transition according to our present results. CD38 expression is a key determinant in the susceptibility of MM cells to daratumumab and is important to evaluate at diagnosis 26…”

“…25 A decrease in the expression of these two markers has been observed in MM with poor prognosis, reinforcing the association of the loss of CD27 and CD38 with MM that we observed in our study. 25 The loss of CD38 is known between SMM and MM transition 21 and is meant to be extended to the MGUS-SMM-MM transition according to our present results. CD38 expression is a key determinant in the susceptibility of MM cells to daratumumab and is important to evaluate at diagnosis.…”

“…15 We found an 84% abnormal PC cut-off to be able to differentiate between MGUS and MM, than the 95% threshold described previously. 13,21 This finding must be explained by the use of the Gini index to classify MGUS-SMM-MM. 18 This parameter was associated in our present study with the PC ratios and the PC ratios were decisive in the decisionmaking process, but they only allowed the classification of a proportion of the cohort.…”