Daratumumab (HuMax®-CD38) Safety Study in Multiple Myeloma

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

Time frame: Up to Week 28 (for Part 1) and up to approximately 2.5 years (for Part 2)

Population: All-Treated Analysis Set included all enrolled participants who received at least 1 dose of study drug.

Overall response defined as percentage of participants who achieved stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR). Per IMWG criteria, sCR: is defined as normal free light chain (FLC) ratio, and absence of clonal plasma cells (PCs) by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry; CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \< 5 % plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or \>= 90% reduction in serum M-protein plus urine M-protein level \< 100mg/24 hours; PR: \>= 50 % reduction of serum M-protein and reduction in 24 hour urinary M-protein by \>= 90% or to \<200 mg/24 hours; if the serum and urine M-protein are not measurable, a decrease of \>=50% in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria.

Time frame: Up to Week 28 (for Part 1) and Week 27 (for Part 2)

Population: All-Treated Analysis Set included all enrolled participants who received at least 1 dose of study drug. For Part 1, only participants treated with \>= 4 mg/kg daratumumab were used for efficacy analyses and less than (\<) 4 mg/kg doses were considered under the therapeutic levels.

Time to first response was defined as the time from the date of first dose of daratumumab to the date of initial documentation of a response (PR or better). Time to best response was defined as the time between the date of first dose of daratumumab and the date of the initial evaluation of the best response (PR or better) to treatment. Kaplan-Meier method was used to estimate the distribution of time to response and time to best response.

Time frame: Up to Week 28

Population: All-Treated Analysis Set included all enrolled participants who received at least 1 dose of study drug. For Part 1, only participants treated with \>= 4 mg/kg daratumumab were used for efficacy analyses and less than (\<) 4 mg/kg doses were considered under the therapeutic levels.

Duration of response was calculated from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the International Myeloma Working Group (IMWG) criteria.

Time frame: Up to Week 27

Population: Subset of All-Treated Analysis Set included those who had overall response in Part 2.

Overall Survival (OS) was defined as the number of days from administration of the first infusion (Day 1) to date of death. Median Overall Survival was estimated by using the Kaplan-Meier method.

Time frame: Approximately 3 years

Population: All-Treated Analysis Set included all enrolled participants who received at least 1 dose of study drug.

Progression free survival (PFS) was defined as the time between the date of first dose of daratumumab and either disease progression or death, whichever occurs first.

Time frame: Up to Week 27

Population: All-Treated Analysis Set included all enrolled participants who received at least 1 dose of study drug.

TTP was defined as the number of days from the date of first infusion (Day 1) to the date of first record of disease progression. Disease progression (IMWG criteria): increase of 25 percent (%) from lowest response level in Serum M-component and/or (the absolute increase must be \>=0.5 g/dL); urine M-component and/or (the absolute increase must be \>=200 mg/24 hour; only in participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain levels (absolute increase must be \>10 mg/dL); Development of hypercalcemia (corrected serum calcium \>11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder. Median TTP was estimated by using the Kaplan-Meier method.

Time frame: Up to Week 27

Population: All-Treated Analysis Set included all enrolled participants who received at least 1 dose of study drug.

Time to first response was defined as the time from the date of first dose of daratumumab to the date of initial documentation of a response (PR or better). Time to best response was defined as the time between the date of first dose of daratumumab and the date of the initial evaluation of the best response (PR or better) to treatment. Time to VGPR (very good partial response) was defined as the time from the date of first dose of daratumumab to the date of initial documentation of VGPR response. The Kaplan-Meier method was used to estimate time to response.

Time frame: Up to Week 27

Population: All-Treated Analysis Set included all enrolled participants who received at least 1 dose of study drug. Here 'n' (Number of Participants Analyzed) signifies number of participants analyzed at specific time point.