Circulating Multiple Myeloma Cells (CMMCs) as Prognostic and Predictive Markers in Multiple Myeloma and Smouldering MM Patients.

Simple Summary: Although liquid biopsy has emerged as a viable substitute, bone marrow (BM) is still the gold standard for the diagnosis and follow-up of patients with multiple myeloma (MM) and smouldering MM (SMM). The potential involvement of circulating MM cells (CMMCs), counted via CELLSEARCH^®, in monitoring disease dynamics was assessed by measuring them during treatment and correlating the results with the prognoses of the patients. For MM and SMM patients, the median numbers of CMMCs counted at diagnosis were 349 (1 to 39,940) and 327 (range 22–2463), respectively. Among SMM patients, higher CMMCs were associated with a greater propensity to evolve (p = 0.042). The CMMC counts in the MM patients showed a significant correlation (p < 0.04) with serum albumin and monoclonal component concentration. Under therapy, CMMCs were consistently detectable in 15/40 patients (coMMstant = 1), and correlated with lower responses (p = 0.04) and survival probability (p = 0.047), suggesting that CMMC persistence is linked to poor prognoses. In recent years, liquid biopsy has emerged as a promising alternative to the bone marrow (BM) examination, since it is a minimally invasive technique allowing serial monitoring. Circulating multiple myeloma cells (CMMCs) enumerated using CELLSEARCH^® were correlated with patients' prognosis and measured under treatment to assess their role in monitoring disease dynamics. Forty-four MM and seven smouldering MM (SMM) patients were studied. The CMMC medians at diagnosis were 349 (1 to 39,940) and 327 (range 22–2463) for MM and SMM, respectively. In the MM patients, the CMMC count was correlated with serum albumin, calcium, β2-microglobulin, and monoclonal components (p < 0.04). Under therapy, the CMMCs were consistently detectable in 15/40 patients (coMMstant = 1) and were undetectable or decreasing in 25/40 patients (coMMstant = 0). High-quality response rates were lower in the coMMstant = 1 group (p = 0.04), with a 7.8-fold higher risk of death (p = 0.039), suggesting that continuous CMMC release is correlated with poor responses. In four MM patients, a single-cell DNA sequencing analysis on residual CMMCs confirmed the genomic pattern of the aberrations observed in the BM samples, also highlighting the presence of emerging clones. The CMMC kinetics during treatment were used to separate the patients into two subgroups based on the coMMstant index, with different responses and survival probabilities, providing evidence that CMMC persistence is associated with a poor disease course. [ABSTRACT FROM AUTHOR]