**5.2 Daratumumab in SMM**

Smouldering myeloma is defined by a medullar infiltration of clonal plasmacells ≥10% in the absence of symptoms. According to the Mayo Clinic criteria, M-protein >2 g/dl, medullar infiltration ≥20% and free-light chain ratio > 20 define risk categories. Patients with one, two and three of these criteria are considered to be at low, intermediate and high risk with 5-year progression of 23% in the low risk, 47% in the intermediate risk and 82% in the high risk [41]. However, in spite of the important risk of transformation into symptomatic disease, current guidelines recommend "watch and wait" even in people with high and intermediate risk smouldering myeloma. Since the earlier intervention may delay progression, different studies are evaluating the use of new drugs in this subset of patients. Daratumumab could be the perfect drug, given the efficacy and the tolerability showed in other subsets. Based on the good results of the CENTAURUS trial, a phase II study for patients with intermediate and high risk smouldering multiple myeloma, randomly assigned, in a 1:1:1 ratio, to receive one of three different schedules of daratumumab [42], a phase III trial has been designed (NCT03301220). In this study, patients with high-risk smouldering myeloma are randomized either to receive subcutaneous daratumumab or to be just monitored. Daratumumab is administered according to the usual schedule, until 39 cycles or up to 36 months or until confirmed disease progression or unacceptable toxicity. This study recently completed the enrolment and the results are still awaited but all the most recent findings suggest that the anti-CD38 could be used with safety and efficacy also in smouldering myeloma.
