Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

All Drugs and Chemicals

Dexamethasone

Prednisone

Melphalan

Bortezomib

Daratumumab

Dexamethasone acetate

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunosuppressive Agents

Immunologic Factors

Participants will receive velcade (bortezomib) 1.3 milligram per square meter (mg/m\^2) as subcutaneous injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at Weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2 , orally, once daily (on Days 1-4) and prednisone 60 mg/m\^2, orally, once daily, on Days 1 to 4 of each cycle up to Cycle 9.

Participants will receive velcade 1.3 mg/m\^2 as SC injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at Weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2, orally, once daily (on Days 1-4) and prednisone 60 mg/m\^2, orally, once daily, on Days 1 to 4 of each cycle up to Cycle 9. In addition participants will also receive daratumumab 16 mg/kg as IV infusion, once weekly, for 6 weeks in Cycle 1 and then every 3 weeks, in Cycle 2 to 9 and thereafter, once every 4 weeks until documented progression, unacceptable toxicity, or until the end of study. On days when daratumumab is given, dexamethasone 20 mg IV or PO is given 1 hour or less prior to daratumumab administration as pre medication and prednisone substitute, and prednisone 60 mg/m2 once daily will be given on Days 2-4. Following amendment 7, participants will have the option to switch to daratumumab subcutaneous (SC) on Day 1 of any cycle, at the discretion of the investigator.

Participants will receive velcade 1.3 mg/m\^2, as subcutaneous injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at Weeks 1, 2, 4 and 5 in Cycles 2 to 9.

Velcade

Participants will receive melphalan 9 mg/m\^2, orally, once daily on Days 1 to 4 of each cycle up to Cycle 9.

Participants will receive prednisone 60 mg/m\^2, orally, once daily, on Days 1 to 4 of each cycle up to Cycle 9.

Participants will receive daratumumab 16 mg/kg as intravenous infusion, once weekly, for 6 weeks in Cycle 1 and then once every 3 weeks, in Cycle 2 to 9 and thereafter, once every 4 weeks until documented progression, unacceptable toxicity, or until the end of study .

Daratumumab IV

Participants administered with dexamethasone 20 mg IV or PO is given 1 hour or less prior to daratumumab administration as pre medication and prednisone substitute.

Daratumumab SC will be administered by SC injection at a fixed dose of 1800 mg once every 4 weeks until documented progression, unacceptable toxicity, or until the end of study. Following amendment 7, participants can switch from daratumumab IV to daratumumab SC.

Daratumumab SC

Janssen Research & Development, LLC Clinical Trial

The purpose of this study is to determine if the addition of daratumumab to velcade (bortezomib) melphalan-prednisone (VMP) will prolong progression-free survival (PFS) compared with VMP alone in participants with previously untreated multiple myeloma who are ineligible for high dose chemotherapy and autologous stem cell transplant (ASCT).

The study consists of 3 phases: Screening Phase (within 21 days prior to randomization), Treatment Phase (Cycle 1 Day 1 to discontinuation of all study treatment), and Follow-up Phase (from discontinuation of all study treatment up to death, lost to follow up, withdrawal of consent, or the study ends, whichever occurs first). Treatment phase will include 2 treatments (Treatment A: participants will receive Velcade MelphalanPrednisone (VMP) alone and Treatment B: participants will receive daratumumab in combination with VMP).Two interim analyses are planned. The first will be to evaluate safety after a total of approximately 100 participants have been treated for at least 2 cycles or discontinued the study treatment. The second will be to evaluate cumulative interim safety and efficacy data, and will be performed when approximately 216 PFS events have been accumulated. The final OS analysis will occur when approximately 382 deaths have occurred. Efficacy will be primarily measured by comparison of PFS between the two treatment arms. Participants' safety will be monitored throughout the study.

A Study of Combination of Daratumumab and Velcade (Bortezomib) Melphalan-Prednisone (DVMP) Compared to Velcade Melphalan-Prednisone (VMP) in Participants With Previously Untreated Multiple Myeloma

A Phase 3, Randomized, Controlled, Open-label Study of VELCADE (Bortezomib) Melphalan-Prednisone (VMP) Compared to Daratumumab in Combination With VMP (D-VMP), in Subjects With Previously Untreated Multiple Myeloma Who Are Ineligible for High-dose Therapy

PFS- duration from date of randomization to Progressive disease (PD)/death, whichever occurs first. PD per IMWG criteria-Increase of 25% from lowest response value in one of following: Serum and urine M-component (absolute increase \>=0.5 gram per deciliter \[g/dL\] and \>=200 milligram \[mg\]/24 hours respectively); Only participants without measurable serum and urine M-protein levels: difference between involved and uninvolved free light chain (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 Plasma cells (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.

The Overall response rate was defined as the percentage of participants who achieved a partial response (PR) or better, according to the International Myeloma Working Group (IMWG) criteria, during the study or during follow up. IMWG criteria for PR: greater than or equal to (\>=) 50 percentage(%) 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 free light chain (FLC) levels is required in 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 bone marrow plasma cells (PCs) is required in place of M-protein, provided baseline bone marrow plasma cell percentage 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.

VGPR or better rate was defined as the percentage of participants who achieved VGPR or complete response (CR) (including stringent complete response\[sCR\]) according to the IMWG criteria during or after the study treatment. VGPR: Serum and urine component detectable by immunofixation but not on electrophoresis, or \>= 90% reduction in serum M-protein plus urine M-protein level less than (\<) 100 milligram (mg) per 24 hour; CR: negative immunofixation on the serum and urine, Disappearance of any soft tissue plasmacytomas and \< 5% plasms cells (PCs) in bone marrow; sCR: CR in addition to having a normal FLC ratio and an absence of clonal cells in bone marrow by immunohistochemistry, immunofluorescence, 2-4 color flow cytometry.

CR or better rate was defined as the percentage of participants with a CR or better (i.e. CR and sCR) as per IMWG criteria. CR: as negative immunofixation on the serum and urine and disappearance of soft tissue plasmacytomas and less than (\<) 5 percent plasma cells in bone marrow; sCR: CR plus normal free light chain (FLC) ratio and absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry.

The Minimal Residual Disease negativity rate was defined as the percentage of participants who had negative MRD (detection of less than 1 malignant cell among 100,000 normal cells) assessment at any timepoint after the first dose of study drugs by evaluation of bone marrow aspirates or whole blood at 10\^-5 threshold. MRD was evaluated by using Deoxyribonucleic acid (DNA) sequencing of immunoglobulin genes. MRD was assessed in participants who achieved complete response or stringent complete response (CR/sCR).

Overall Survival (OS) was defined as the number of days the date of randomization to date of death. Median Overall Survival was estimated by using the Kaplan-Meier method.

Progression-free survival after next-line therapy is defined as the time from randomization to progression on the next line of subsequent antimyeloma therapy or death due to any cause (prior to start of second line of antimyeloma therapy), whichever comes first. Disease progression on next line of treatment was based on investigator judgment.

sCR as per IMWG criteria is CR plus normal free light chain (FLC) ratio and absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry. CR: Negative immunofixation on the serum and urine; Disappearance of any soft tissue plasmacytomas; \<5% plasma cells (PCs) in bone marrow.

TTP: Time from date of randomization to date of first documented evidence of PD or death due to PD, whichever occurs first. PD per IMWG criteria- Increase of 25 % from lowest response value in one of following: Serum and urine M-component (absolute increase \>=0.5 gram per deciliter \[g/dL\] and \>=200 mg/24 hours respectively); Only in participants without measurable serum and urine M-protein levels: difference between involved and uninvolved FLC levels (absolute increase \>10 milligram per deciliter \[mg/dL\]); Only in participants without measurable serum and urine M-protein levels and without measurable disease by FLC levels, bone marrow plasma cells (PC)% (absolute % \>=10%); Bone marrow PC %: absolute % \>10%; Definite development of new bone lesions/soft tissue plasmacytomas or 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.

Time to response, defined as the time between the date of randomization and the first efficacy evaluation that the participant has met all criteria for PR or better. 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; If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, \>=50% reduction in bone marrow PCs is required in place of M-protein, provided baseline bone marrow plasma cell percentage was \>=30%.

DOR: participants with a confirmed response (PR or better) as time between first documentation of response and disease progression, IMWG response criteria, or death due to PD, whichever occurs first. PD: Increase of 25% from lowest response value in any one of following: Serum M-component (absolute increase\>=0.5 g/dL); Urine M-component (absolute increase\>=200 mg/24 hours); 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 and without measurable disease by FLC levels, bone marrow PC%(absolute%\>=10%); Bone marrow PC's %: absolute%\>10%; Definite development of new bone lesions/soft tissue plasmacytomas/definite increase in the size of existing bone lesions or soft tissue plasmacytomas and Development of hypercalcemia (corrected serum calcium \>11.5 mg/dL) that can be attributed solely to PC proliferative disorder.

Time to next treatment is defined as the time from randomization to the start of the next-line treatment.

Percentage of participants with Best M- protein response of 100% reduction and \>=90% to \< 100% reduction were assessed. Best M-protein response was defined as the maximal percent reduction or the lowest percent increase from baseline in serum M-protein for participants with measurable heavy chain at baseline or urine M-protein for participants without measurable heavy chain, but with measurable light chain disease at baseline. For participants without measurable heavy chain and light chain disease at baseline, best response in serum free light chain (FLC) was defined as the maximal percent reduction or the lowest percent increase from baseline in the difference between involved and uninvolved serum FLC level (dFLC).

The EORTC QLQ-C30 is a 30 items self-reporting questionnaire, with a 1 week recall period, resulting in 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 Global Health Status (GHS) scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The questionnaire includes 28 items with 4-point Likert type responses from "1-not at all" to "4-very much" to assess functioning and symptoms; 2 items with 7-point Likert scales (1= poor and 7= excellent) for global health and overall QoL. Scores are transformed to a 0 to 100 scale, with higher scores representing better GHS, better functioning, and more symptoms. Negative change from baseline values indicate deterioration in quality of life or functioning and positive values indicate improvement.

EQ-5D-5L is a standardized, participant-rated questionnaire to assess health-related quality of life. The EQ-5D-5L includes 2 components: the EQ-5D-5L health state profile (descriptive system) and the EQ-5D-5L Visual Analog Scale. The Visual Analogue Scale is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state.

EQ-5D-5L is a standardized, participant-rated questionnaire to assess health-related quality of life. The EQ-5D-5L includes 2 components: the EQ-5D-5L health state profile (descriptive system) and the EQ-5D-5L Visual Analog Scale. The EQ-5D-5L descriptive system provides a profile of the participant's health state 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response options (no problems, slight problems, moderate problems, severe problems and extreme problems) that reflect increasing levels of difficulty. The participant was asked to indicate his/her current health state by selecting the most appropriate level in each of the 5 dimensions. Responses to the 5 dimension scores were combined and converted into a single preference-weighted health utility index score 0 (0.0- worst health state) to 1 (1.0- better health state) representing the general health status of the individual based on the UK scoring algorithm.

Janssen Research & Development, LLC

Safety population defined as participants who have received at least 1 administration of any study drug.

Participants received Velcade (bortezomib) 1.3 milligram per square meter (mg/m\^2) as subcutaneous (SC) injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at Weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2 orally once daily on Days 1 to 4 and prednisone 60 mg/m\^2 orally once daily on Days 1 to 4 of each cycle up to Cycle 9.

Velcade, Melphalan and Prednisone (VMP)

Participants received velcade 1.3 mg/m\^2 as SC injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2, orally once daily on Days 1 to 4 and prednisone 60 mg/m\^2, orally once daily on Days 2 to 4 of each cycle up to Cycle 9. In addition, participants also received daratumumab 16 milligram per kilogram (mg/kg) as intravenous (IV) infusion once weekly for 6 weeks in Cycle 1 and then every 3 weeks, in Cycle 2 to 9 and thereafter, once every 4 weeks until documented progression, unacceptable toxicity, or study end. On Day 1 of each cycle, dexamethasone 20 mg IV or per oral (PO) was given 1 hour or less prior to daratumumab infusion as pre medication and prednisone substitute.

Daratumumab, Velcade, Melphalan and Prednisone (D-VMP)

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Argentina

Australia

Belgium

Brazil

Bulgaria

Croatia

Czech Republic

Georgia

Germany

Greece

Hungary

Italy

Japan

Poland

Portugal

Macedonia

Romania

Russia

Serbia

Korea, Democratic People'S Republic Of

Spain

Turkey

Ukraine

United Kingdom

United States

Region of Enrollment

The International Staging System (ISS) consists of following 3 stages - Stage I: serum beta2-microglobulin less than (\<)3.5 milligram per liter (mg/L) and albumin greater than or equal to (\>=) 3.5 gram per 100 Milliliter (g/100 mL); Stage II: neither stage I nor stage III and Stage III: serum beta2-microglobulin \>= 5.5 mg/L.

Here, 'N' (number of participants analyzed) signifies number of participants who were evaluable for this study specific characteristic.

Stage of Disease (ISS)

Time from multiple myeloma (MM) diagnosis is the time from diagnosis of multiple myeloma to randomization in each treatment group.

Time from multiple myeloma (MM) diagnosis

Executive Medical Director

Intent-to-treat (ITT) population included all participants randomized into the study; classified according to assigned treatment group, regardless of the actual treatment received.

Progression Free Survival (PFS)

ITT population included all participants randomized into the study; classified according to assigned treatment group, regardless of the actual treatment received.

Overall Response Rate (ORR)

Percentage of Participants With Very Good Partial Response (VGPR) or Better

Percentage of Participants With Complete Response (CR) or Better

Percentage of Participants With Negative Minimal Residual Disease (MRD)

Overall Survival (OS)

Progression Free Survival on Next Line of Therapy (PFS2)

Percentage of Participants With Stringent Complete Response (sCR)

Time to Disease Progression (TTP)

Response-evaluable population: participants who have a confirmed diagnosis of MM and measurable disease at baseline or screening, must receive at least one component of study treatment and have adequate post-baseline disease assessments. "N" (number of participants analyzed) signifies number of participants evaluable for this endpoint.

Time to Response

Response-evaluable set: participants who have a confirmed diagnosis of MM and measurable disease at baseline or screening. Participants must have received at least one component of study treatment and have adequate post-baseline disease assessments. "N"(number of participants analyzed) signifies number of participants evaluable for this endpoint.

Duration of Response (DOR)

Time to Next Treatment (TNT)

Best M-protein response in serum: 100% reduction

Best M-protein response in serum:>= 90 to < 100%

Best M-protein response in urine:100% reduction

Best M-protein response in urine:>=90 to < 100%

Best response in dFLC:100% reduction

Best response in dFLC: >=90% to < 100% reduction

Response-evaluable set: participants have confirmed diagnosis of MM and measurable disease at baseline or screening. Participants must receive at least one component of study treatment, have adequate post-baseline disease assessments. 'n' (number of participants analyzed) signifies number of participants analyzed for each specified category.

Percentage of Participants With Best M-protein Response

Month 3

Month 6

Month 9

Month 12

Month 18

ITT population: participants randomized into the study; classified according to assigned treatment group,regardless actual treatment received. 'N' (number of participants analyzed) signifies participants evaluable for this endpoint and 'n' signifies number of participants who were analyzed at each specified timepoint, for each arm, respectively.

Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30: Emotional Functioning Score

Baseline

Change From Baseline in EuroQol-5 Dimensions-5 Levels (EQ-5D-5L): Visual Analogue Scale (VAS)

Change From Baseline in EuroQol 5 Dimensions-5 Level (EQ-5D-5L) Utility Score

Overall Study

Lenalidomide

Angiogenesis Inhibitors

Growth Inhibitors

Participants will receive Lenalidomide 25 mg capsule orally on Day 1 through Day 21 of each 28-day cycle, Dexamethasone 40 mg orally or intravenously once a week. Study treatment continues until disease progression, unacceptable toxicity, or end of study (maximum up to 7 years after last subject is randomized) whichever comes first.

Participants will receive Daratumumab 16 milligram per kilogram (mg/kg) by intravenous infusion, once a week for 8 weeks, then once every other week for 16 weeks, thereafter once every 4 weeks, Lenalidomide 25 mg capsule orally on Day 1 through Day 21 of each 28-day cycle, Dexamethasone 40 mg orally or intravenously once a week. Following implementation of protocol amendment 8, participants still receiving treatment with daratumumab IV will have the option to switch to daratumumab SC on Day 1 of any cycle, at the discretion of the investigator. Daratumumab subcutaneous (SC) will be administered by SC injection at a fixed dose of 1800 mg once every 4 weeks until documented progression, unacceptable toxicity, or study completion. Study treatment continues until disease progression, unacceptable toxicity, or end of study (maximum up to 7 years after last subject is randomized) whichever comes first.

Daratumumab will be administered at a dose of 16 milligram per kilogram (mg/kg) by intravenous (IV) infusion, once a week for 8 weeks, then once every other week for 16 weeks, thereafter once every 4 weeks until documented progression of disease, unacceptable toxicity, or end of study (maximum up to 7 years).

Lenalidomide 25 mg capsule orally on Day 1 through Day 21 of each 28-day cycle.

Dexamethasone 40 mg orally or intravenously once in a week.

Daratumumab SC will be administered by SC injection at a fixed dose of 1800 mg once every 4 weeks until documented progression, unacceptable toxicity, or study end. Following implementation of protocol amendment 8, participants still receiving treatment with daratumumab IV will have the option to switch to daratumumab SC on Day 1 of any cycle, at the discretion of the investigator.

The purpose of this study is to compare the efficacy of daratumumab in combination with lenalidomide and dexamethasone to that of lenalidomide and dexamethasone in terms of progression-free survival (PFS) in participants with newly diagnosed multiple myeloma (a blood cancer of plasma cells) who are not candidates for high dose chemotherapy (treatment of disease, usually cancer, by chemical agents) and autologous stem cell transplant (ASCT).

This is a Phase 3, randomized (study drug assigned by chance), open-label (participants and researchers are aware about the treatment, participants are receiving), active-controlled (study in which the experimental treatment or procedure is compared to a standard treatment or procedure), parallel-group (each group of participants will be treated at the same time), and multicenter (when more than one hospital or medical school team work on a medical research study) study in participants with newly diagnosed multiple myeloma and who are not candidates for high dose chemotherapy and ASCT. All the eligible participants will be randomly assigned to receive either lenalidomide and dexamethasone (Rd) (Arm A) or daratumumab in combination with lenalidomide and dexamethasone (DRd) (Arm B). Daratumumab (16 milligram per kilogram \[mg/kg\]) will be administered weekly for first 8 weeks (Cycles 1 to 2) of treatment and then every other week for 16 weeks (Cycles 3 to 6), then every 4 weeks (from Cycle 7 and beyond) until progression of disease or unacceptable toxicity. Lenalidomide will be administered at a dose of 25 mg orally on Days 1 through 21 of each 28-day cycle, and dexamethasone will be administered at a dose of 40 mg once a week for both treatment arms. Participants in both treatment arms will continue lenalidomide and dexamethasone until disease progression or unacceptable toxicity. All participants randomized to Treatment Arm B (DRd) in this study initially received daratumumab IV formulation; however, following implementation of protocol amendment 8, participants still receiving treatment with daratumumab IV will have the option to switch to daratumumab SC on Day 1 of any cycle, at the discretion of the investigator. Daratumumab subcutaneous (SC) will be administered by SC injection at a fixed dose of 1800 mg once every 4 weeks until documented progression, unacceptable toxicity, or study completion. Participants in Arm A who have sponsor-confirmed disease progression may have the option to receive daratumumab provided by the sponsor (in any subsequent line of therapy) in the Follow-up phase. The study consists of 3 phases: Screening Phase (within 21 days prior to the first dose administration on Day 1), Treatment Phase (Day 1 up to discontinuation of all study treatment), and Follow-up Phase (from discontinuation of all study treatment up to death, lost to follow up, consent withdrawal, or study end, whichever occurs first). The maximum duration of study will be 7 years after last participant is randomized. Efficacy will primarily be evaluated by PFS. Participants' safety will be monitored throughout the study.

Study Comparing Daratumumab, Lenalidomide, and Dexamethasone With Lenalidomide and Dexamethasone in Participants With Previously Untreated Multiple Myeloma

A Phase 3 Study Comparing Daratumumab, Lenalidomide, and Dexamethasone (DRd) vs Lenalidomide and Dexamethasone (Rd) in Subjects With Previously Untreated Multiple Myeloma Who Are Ineligible for High Dose Therapy

PFS is defined as time from date of randomization to either progressive disease (PD) or death, whichever occurs first based on computerized algorithm as per International Myeloma Working Group (IMWG) criteria. PD is defined as an increase of 25 percent (%) from the lowest response value in one of the following: serum and urine M-component (absolute increase must be greater than or equal to \[\>=\] 0.5 gram per deciliter \[g/dL\] and \>=200 milligram \[mg\]/24 hours respectively); Only in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved free light chain (FLC) levels (absolute increase must be greater than \[\>\]10 mg/dL); Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium \>11.5 mg/dL) that can be attributed solely to Plasma cell (PC) proliferative disorder.

CR or better is defined as percentage of participants with a CR or better (CR or stringent complete response \[sCR\]) based on computerized algorithm as per IMWG criteria. CR is defined as negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and less than (\<) 5 percent (%) PCs in bone marrow. In participants with only measurable disease by serum FLC levels a normal serum FLC ratio is required. sCR is defined as in addition to CR a normal FLC ratio, and absence of clonal PCs by immunohistochemistry or immunofluorescence or 2 to 4-color flow cytometry.

VGPR or better is defined as the percentage of participants with a response of VGPR or better (VGPR, CR or sCR) based on computerized algorithm as per IMWG criteria. VGPR is defined as serum and urine M-component detectable by immunofixation but not on electrophoresis or \>=90% reduction in serum M-protein plus urine M-protein \<100 mg/24 hours. In participants with only measurable disease by serum FLC levels a \>90% decrease in the difference between involved and uninvolved FLC levels is required.

MRD negativity rate is defined as the percentage of participants who had negative MRD (detection of less than 1 malignant cell among 100,000 normal cells) assessment at any timepoint after the date of randomization by evaluation of bone marrow aspirates. MRD was assessed in participants who achieved CR or better.

ORR is defined as the percentage of participants who achieved partial response (PR) or better (PR, VGPR, CR or sCR) based on computerized algorithm as per IMWG criteria. PR is defined as \>=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. A \>=50% reduction in the size of soft tissue plasmacytomas is also required.

OS was measured from the date of randomization to the date of the death.

TTP is defined as the time from the date of randomization to the date of PD based on computerized algorithm as per IMWG criteria, or death due to PD.

Time to response is defined as the time from the date of randomization to the first efficacy evaluation that met criteria for PR or better based on computerized algorithm as per IMWG criteria. 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; If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, \>=50% reduction in bone marrow PCs is required. A \>=50% reduction in the size of soft tissue plasmacytomas is also required.

DoR is defined as the time from the date of initial response (PR or better) to the date of PD, based on computerized algorithm as per IMWG criteria.

Time to subsequent anti-myeloma treatment is defined as the time from randomization to the start of first line of subsequent anti-myeloma treatment or death, whichever occurs first.

PFS2 is defined as the time from randomization to progression on the first line of subsequent anti-myeloma therapy or death, whichever occurs first. Disease progression on first line of subsequent anti-myeloma treatment was based on investigator judgment. Participants that were censored for PFS1 were also censored for PFS2.

EORTC QLQ-C30 is 30 items self-reporting questionnaire, with 1 week recall period, resulting in 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 Global Health Status (GHS) scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Questionnaire includes 28 items with 4-point Likert type responses from "1-not at all" to "4-very much" to assess functioning and symptoms; 2 items with 7-point Likert scales (1= poor and 7= excellent) for global health and overall health related QoL. Scores are transformed to 0 to 100 scale, with higher scores representing better GHS, better functioning, and more symptoms. Negative change from baseline values shows deterioration in quality of life or functioning and reduction in symptom and positive values indicate improvement and worsening of symptoms.

EQ-5D-5L is standardized, participant-reported questionnaire to assess health-related quality of life. EQ-5D-5L includes 2 components: EQ-5D-5L health state profile (descriptive system) and EQ-5D-5L VAS. EQ-5D-5L descriptive system provides a profile of participant's health state 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response options (no problems, slight problems, moderate problems, severe problems and extreme problems) that reflect increasing levels of difficulty. The participant was asked to indicate his/her current health state by selecting the most appropriate level in each of the 5 dimensions. Responses to the 5-dimension scores were combined and converted into single preference-weighted health utility index score 0 (0.0- worst health state) to 1 (1.0- better health state) representing the general health status of individual (but allows for values less than 0 by United kingdom \[UK\] scoring algorithm).

Safety population was defined as participants who have received at least 1 administration of any study treatment (partial or complete).

Participants received Lenalidomide 25 milligrams (mg) capsule orally daily on Day 1 through Day 21 of each 28-day cycle, Dexamethasone 40 mg orally or intravenously (IV) once a week (QW) until disease progression or unacceptable toxicity.

Lenalidomide + Dexamethasone (Rd)

Participants received Daratumumab 16 milligrams per kilograms (mg/kg) IV QW for the first 8 weeks (cycles 1-2) and then every 2 weeks (Q2W) for 16 weeks (Cycle 3-6), then every 4 weeks (Q4W) (from Cycle 7 and beyond) (each cycle of 28 days), Lenalidomide 25 mg capsule orally daily on Day 1 through Day 21 of each 28-day cycle, Dexamethasone 40 mg orally or IV QW until disease progression or unacceptable toxicity.

Daratumumab + Lenalidomide + Dexamethasone (DRd)

Race/Ethnicity, Customized

AUSTRALIA

AUSTRIA

BELGIUM

CANADA

DENMARK

FRANCE

GERMANY

IRELAND

ISRAEL

ITALY

NETHERLANDS

SWEDEN

UNITED KINGDOM

UNITED STATES

Stage I

Stage II

Stage III

The International Staging System (ISS) consists of following 3 stages - Stage I: serum beta2-microglobulin less than (\<) 3.5 milligram per liter (mg/L) and albumin greater than or equal to (\>=) 3.5 gram per 100 Milliliter (g/100 mL); Stage II: neither stage I nor stage III and Stage III: serum beta2-microglobulin \>= 5.5 mg/L.

Time from MM diagnosis is the time from diagnosis of multiple myeloma to randomization in each treatment group.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Combination of Daratumumab and Velcade (Bortezomib) Melphalan-Prednisone (DVMP) Compared to Velcade Melphalan-Prednisone (VMP) in Participants With Previously Untreated Multiple Myeloma	NCT02195479	Multiple Myelom...	Velcade Melphalan Prednisone Daratumumab IV Dexamethasone Daratumumab SC	18 Years -	Janssen Research & Development, LLC
Study Comparing Daratumumab, Lenalidomide, and Dexamethasone With Lenalidomide and Dexamethasone in Participants With Previously Untreated Multiple Myeloma	NCT02252172	Multiple Myelom...	Daratumumab IV Lenalidomide Dexamethasone Daratumumab SC	18 Years -	Janssen Research & Development, LLC
A Study of Combination of Daratumumab and Velcade (Bortezomib) Melphalan-Prednisone (DVMP) Compared to Velcade Melphalan-Prednisone (VMP) in Participants With Previously Untreated Multiple Myeloma	NCT02195479	Multiple Myelom...	Velcade Melphalan Prednisone Daratumumab IV Dexamethasone Daratumumab SC	18 Years -	Janssen Research & Development, LLC

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