A Study to Evaluate Dara-CyBorD in Previously Untreated and Relapsed Subjects With Multiple Myeloma

ORR: percentage of participants achieved PR or better (PR,VGPR,CR,sCR) per IMWG. CR:negative immunofixation on serum, urine, disappearance of soft tissue plasmacytomas,<5% PCs in bone marrow(BM). sCR:CR plus normal FLC ratio,absence of clonal cells in BM by immunohistochemistry, immunofluorescence. VGPR:Serum, urine M-protein detectable by immunofixation but not on electrophoresis or >=90% reduction in serum M-protein plus urine M-protein level <100 mg/24hours. PR:>=50% reduction of serum M-protein and reduction in 24hours urinary M-protein by >=90% or to <200mg/24hours. If serum, urine M-protein unmeasurable, a>=50% decrease in difference involved and uninvolved FLC levels required in place of M-protein criteria. If serum, urine M-protein not measurable, serum free light assay is not measurable,>=50% reduction in PCs required in place of M-protein,provided baseline bone marrow PCs% >=30%, if present at baseline, a >=50% reduction in size of soft tissue plasmacytomas is also required.

Time to VGPR or Better response was defined as duration from the date of first dose (start of induction) to the date of initial documentation of the response (VGPR or better) which was confirmed by a repeated measurement as required by the IMWG criteria. VGPR is defined by IMWG criteria as serum and urine M-protein detectable by immunofixation but not on electrophoresis or greater than or equal to (>=) 90 % reduction in serum M-protein plus urine M-protein level < 100 milligram/24 hours (mg/24 hours).

Time to PR or Better response was defined as duration from the date of first dose (start of induction) to the date of initial documentation of the response (PR or better) which was confirmed by a repeated measurement as required by the IMWG criteria. PR is defined as per IMWG criteria as >= 50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by >= 90% or to < 200 mg/24hours. If the serum and urine M-protein are unmeasurable, a>= 50% decrease in the difference between involved and uninvolved Free light chain (FLC) levels is required in the place of the M-protein criteria. If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, >=50% reduction in plasma cells is required in place of M-protein, provided baseline bone marrow plasma cells percentage was >=30%. In addition to the above listed criteria, if present at baseline, a >= 50% reduction in the size of soft tissue plasmacytomas is also required.

DOR was defined for participants with a confirmed response (PR or better) as the duration from the date of initial documentation of a response (PR or better) according to the IMWG criteria to the date of first documented evidence of progressive disease according to the IMWG criteria or death due to progressive disease. PR:>=50% reduction of serum M-protein and reduction in 24hours urinary M-protein by >=90% or to <200 mg/24hours. If serum and urine M-protein are unmeasurable, a >=50% decrease in difference involved and uninvolved FLC levels required in place of M-protein criteria. If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, >=50% reduction in PCs is required in place of M-protein, provided baseline bone marrow PCs % was >=30%. In addition to the above criteria, if present at baseline, a >=50% reduction in the size of soft tissue plasmacytomas is also required.

PFS: duration from date of first dose (start of induction) to date of first documented evidence of progressive disease (PD) based on computerized algorithm per IMWG criteria or death due to any cause, whichever occurred first. PD: 25% increase from lowest response value in one of following: Serum and urine M-component (absolute increase >=0.5 g/dL and >=200 mg/24 hours respectively);Only participants without measurable serum and urine M-protein levels: difference between involved and uninvolved FLC levels (absolute increase>10 mg/dL);Only participants without measurable serum and urine M-protein levels, without measurable disease by FLC levels, bone marrow PC% (absolute % >=10%); Bone marrow PC%: absolute% >10%; Definite development of new bone lesions/soft tissue plasmacytomas/definite increase in size of existing bone lesions/soft tissue plasmacytomas, Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder.

TTP was defined as the time between the date of first dose (start of induction) and the date of first documented evidence of confirmed PD, as defined in the IMWG response criteria. PD per IMWG criteria: Increase of 25% from lowest response value in one of following: Serum and urine M-component (absolute increase >=0.5 g/deciliter (dL) and >=200 mg/24 hours respectively); Only participants without measurable serum and urine M-protein levels: difference between involved and uninvolved FLC levels (absolute increase>10 mg/dL); Only participants without measurable serum and urine M-protein levels, without measurable disease by FLC levels, bone marrow PC% (absolute % >=10%); Bone marrow PC%: absolute% >10%; Definite development of new bone lesions/soft tissue plasmacytomas/definite increase in size of existing bone lesions/soft tissue plasmacytomas and Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to the PC proliferative disorder.

Overall survival (OS) was measured from the date of first dose (start of induction) to the date of death due to any cause.

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent were events between administration of study drug and approximately up to 36 months that were absent before treatment or that worsened relative to pre-treatment state.