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All NVP-BGJ398 in vitro patients recovered from their SAEs with treatment and the maximum tolerated dose has not yet been reached. There was a dose-dependent decrease in peripheral-blood NK cells that was noted, with full recovery after treatment [Lokhorst et al. 2013]. In this phase I/II study, daratumumab displayed a dose-dependent efficacy with greater decreases in paraprotein levels seen in patients at higher doses. A high area under the curve correlated with prolonged PFS. Biochemical responses were accompanied by clearance of MM cells from the bone marrow. Four patients achieved a partial response (PR), six had a minimal response, while five had stable disease by International Myeloma Working Group criteria. Building upon initial results, the GEN501 expansion served to evaluate safety and efficacy of 2 doses of daratumumab (8?mg/kg, at three different infusion times, or 16?mg/kg once a week for 8 weeks, followed by 8 doses twice monthly and monthly dosing up to 24 months) [Lokhorst et al. 2014]. The phase II part of the trial has recruited 50 patients so far; 30 patients received the 8?mg/kg dosing and 20 the 16?mg/kg dosing. Fever, fatigue, upper respiratory tract infection, dyspnea, cough and diarrhea were the most common adverse events and were reported in more than 20% of patients. Mild (grade 1 and 2) IREs occurred in 27% of patients in the 16 mg/kg group and 20% of the 8 mg/kg group, and there were no reports of severe IREs. There were two cases of SAEs between the two groups: one case of thrombocytopenia and one case of lymphopenia. Omission of the predose did not have an impact on the incidence and severity of IREs [Lokhorst et al. 2014]. Investigators did not observe any dose-related increases in side effects. Although this phase I/II study did not include a quality of life analysis with daratumumab therapy, it is encouraging to note that, except for IREs, there were no major side effects and the drug was very well tolerated. Of the 30 patients in 8?mg/kg dosing groups, 10% responded, and all were partial responses (PRs). The overall response rate (RR) was much higher in the 16?mg/kg dosing group where 35% of the 20 patients responded, with 10% achieving a complete response (CR), 5% a very good partial response (VGPR), and 20% a PR. The median PFS was 15 months in the 8?mg/kg dosing groups, compared with 23 months in the 16?mg/kg dosing group. The dose of 16?mg/kg achieves deeper responses and is presumed to be target-saturating and therefore, is the dose that has been used in subsequent trials. More mature results of the study will inform if extended exposure with daratumumab monotherapy for up to 24 months in responding patients will further prolong the PFS. Ongoing clinical trials The early results of daratumumab used as a single agent are impressive. Considerable responses have been observed in a cohort of heavily pretreated patients with relapsed/refractory MM.