Selection of populations of MM cells with high expression of complement-inhibitory proteins during therapy with daratumumab. Two of 21 GEN501 patients had coexisting populations of MM cells, which differed in CD55 and/or CD59 expression. (A) BM-localized MM cells from patient 5 differed in expression levels of CD55 (absent or strongly positive) and CD59 (absent or strongly positive). Bone marrow samples were obtained before start of daratumumab therapy, at the time of progressive disease (PD), and 6 months after the last daratumumab infusion. Flow cytometry histograms for these samples are shown. (B) Similarly, circulating MM cells from patient 5 also differed in expression levels of CD55 (absent or strongly positive) and CD59 (absent or strongly positive). Serial blood samples were obtained during daratumumab monotherapy and during the treatment given after development of progressive disease (PD). Longitudinal data representation of absolute circulating MM cell counts over time and of the frequency of the different subpopulations based on complement-inhibitory protein expression. Representative histograms are also shown for this patient. RAD, lenalidomide, adriamycin, and dexamethasone.