1.Background: Patients with multiple myeloma (MM) relapsed or refractory to current treatment options and ineligible for ASCT have a poor prognosis.Therefore new treatment options are highly needed for this patient population.Daratumumab is a human IgG1κ monoclonal antibody that targets CD38.Malignant MM cells exhibit very strong CD38 surface expression.The major mechanisms of action of daratumumab are complement dependent cytotoxicity and antibody dependent cell-mediated cytotoxicity.Daratumumab has been shown to inhibit growth of CD38-expression tumor cells in SCID mouse xenografts.We report the preliminary safety results from the ongoing first in man doseescalation study (clin.trial.gov.NCT00574288).2.Methods: Patients (age > 18 yrs) ineligible for ASCT and relapsed or refractory to at least two different prior therapies.Patients receive 7 full and 2 pre-dose infusions of daratumumab (1st pre-dose day 1, 1st full dose day 2, 2nd pro-dose day 21, 2nd full-dose day 22 and thereafter weekly full-dose daratumumab).The study design encompasses a classic 3 + 3 dose escalation with the possibility to limit exposure to 1 patient in the first 2 cohorts pending safety data.The dose range is from 0.005 mg/kg to 24 mg/kg.The primary objective is to establish the safety profile and secondary objectives are to establish MTD and evaluate the efficacy.An independent Data Monitoring Committee evaluates the safety data for each cohort before doseescalation.3.Results: Until Nov 24th, 2011 safety data for 23 patients, including dose range from 0.005 mg/kg up to 4 mg/kg cohort, were collected.Median age 64 yrs (42-76), F/M:9/14, The patients had received median 6 (2-10) prior treatments.The most common AEs reported in more than 2 patients are pyrexia (30%), free hemoglobin (22%), anemia (22%),cough (22%), dizziness (17%), hemolysis (17%), influenza-like-illness (13%), nausea (13%) lymphopenia (13%),monocytopenia (13%).Five SAE were assessed as related to daratumumab.One patient had anemia grade 3 and thrombocytopenia grade 4, one patient experienced cytokine release syndrome grade 2 and based on these DLT events 3 more patients were enrolled in the 0.1 mg/kg and 1.0mg/kg cohorts, one patient experienced a grade 3 bronchospasm 40 hours after end of trial drug infusion and one patient had AST elevation.All patients recovered after relevant treatment.Since implementation of relevant pre-medication and dilution of trial drug no severe infusion related AEs have been reported.In the 4mg/kg cohort the maximal reduction in M-component was 49%, 55% and 61% respectively,and dosing was still ongoing in the patient with a 61% reduction.A complete data set will be presented at the meeting.4.Conclusion: Daratumumab has a manageable safety profile as monotherapy in patients with multiple myeloma in doses up to and including 4 mg/kg.The dose-escalation is ongoing and further data will be presented at the meeting.