Optimal risk stratification is necessary for early intervention in smoldering multiple myeloma (SMM) to prevent under- and overtreatment. Researchers hypothesized that the International Myeloma Working Group 20/2/20 model could be enhanced by swapping out bone marrow (BM) plasma cells (PC) for circulating tumor cells (CTC) and by adding immune biomarkers in peripheral blood (PB) for the identification of patients at risk of progression due to lost immune surveillance. Here, they detailed the outcomes of 150 patients with SMM who participated in the iMMunocell research, in which tumor and immune cells in PB were assessed serially every 6 months for 3 years. 

The median time to progression was 17 months for patients with CTCs more than 0.015% versus not reached for those with CTCs less than or equal to 0.015% at baseline (HR, 4.9; P < 0.001). A multivariate analysis including serum-free light-chain ratio more than 20, more than 2 g/dL M-protein, and more than 0.015% CTCs found that the presence of more than 20% BM PCs had little predictive value. Similar risk stratification was obtained using the 20/2/20 and 20/2/0.015 models (C-index of 0.76 and 0.78). 

Patients were stratified into low, intermediate-low, high, and high-risk diseases with 0, 20%, 39%, and 73% rates of progression after 2 years using the 20/2/0.015 model in conjunction with an immune risk score based on the percentages of SLAN+ and SLAN nonclassical monocytes, CD69+HLADR+ cytotoxic NK cells, and CD4+CXCR3+ stem central memory T cells. It was found in this investigation that CTCs are superior to BM PCs for gauging tumor load. Defining a consensus cutoff of CTCs for non-invasively stratifying SMM requires more study in bigger datasets.

Source: aacrjournals.org/clincancerres/article-abstract/28/21/4771/709838/Circulating-Tumor-and-Immune-Cells-for-Minimally?redirectedFrom=fulltext