*1.2.1. Circulating tumour cells (CTC)*

CTC are intact tumour cells that disengage from tumour sites thus entering the circulation and are a recognised feature of metastatic cancers [23–25]. Historically, CTC were considered to be present only in a sub-set of ND, untreated or end-stage MM patients. Now with the advent of highly sensitive next-generation (NG) flow cytometry techniques the detection of CTC in pre-malignant MGUS and at different stages in MM has become feasible [26–28] and CTC can be detected in the peripheral blood of a substantial proportion of MM patients evaluated in this fashion [29, 30]. Importantly, the numbers of CTC in the peripheral blood in MM patients with active disease is known to be significantly higher than in patients with inactive disease, with higher numbers of CTC being a risk factor for progression to symptomatic MM for patients with either MGUS or smouldering MM (SMM) [29–33]. The number of CTC in ND and RR patients is also known to be an independent prognostic factor for survival [34–37]. Finally, the absolute numbers of CTC was found in one study to be a better predictor of disease activity than SFLC ratios [30].
