The median overall survival as measured from the start of treatment until the time of death due to any cause.

Median amount of time from the start of treatment until first documented response as defined by the International Myeloma Working Group uniform response criteria

Stringent CR: Same as CR plus normal free light chain ratio and absence of clonal cells plasma cells in bone marrow (BM) CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and <5% plasma cells in BM VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level <100 mg per 24 hours PR: ≥50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ≥90% or to <200 mg per 24 hours. If the serum and urinary M-protein are not measurable, additional criteria are used to assess PR that will not fit in the space provided here. If present at baseline, a ≥50% reduction in the size of plasmacytomas is also required

Response rate was assessed using the International Myeloma Working Group uniform response criteria. Stringent complete response, Complete Response, Very Good Partial Response, and Partial Response are defined in outcome measure 1.

• MR included participants in whom some, but not all, criteria for PR were fulfilled, providing the remaining criteria satisfied the requirements for MR. Required all of the following:

  • ≥25% to ≤ 49% reduction in the level of serum monoclonal protein for at least two determinations six weeks apart.
  • If present, a 50 to 89% reduction in 24-hour light chain excretion, which still exceeds 200 mg/24 h, for at least two determinations six weeks apart.
  • 25-49% reduction in the size of plasmacytomas (by clinical or radiographic examination) for at least six weeks.
  • No increase in size or number of lytic bone lesions (development of compression fracture does not exclude response).

• Stable Disease: Not meeting the criteria for minimal response or

The pharmacokinetic profile of intravenous and subcutaneous bortezomib administration in combination with lenalidomide and dexamethasone.

To evaluate pharmacogenomic markers among patients with treatment related polyneuropathy.

International Staging System for Multiple Myeloma, divides multiple myeloma into three categories with III representing more advanced disease and I less advanced disease

Stage I :

• Serum beta-2 microglobulin is less than 3.5 mg/L
• AND Albumin level is 3.5 g/dL or greater
• AND Cytogenetics are considered "not high risk"
• AND Lactate dehydrogenase (LDH) levels are normal

Stage II: Not stage I or stage II

Stage III:

• Serum beta-2 microglobulin is 5.5 (mg/L) or greater
• AND Cytogenetics are considered "high-risk"
• AND/OR LDH levels are high

Stage III represents more advanced disease and stage I less advanced.

Stage I:

• Hemoglobin value 10 g/dL
• Serum calcium value normal or =12 mg/dL
• Bone x-ray, normal bone structure (scale 0) or solitary bone plasmacytoma only
• Low M-component production rate (IgG value <5 g/dL; IgA value <3 g/dL; Bence Jones protein <4 g/24 hr)

Stage II:

Neither stage I nor stage III

Stage III:

On or more of the following:

• Hemoglobin value 12 mg/dL
• Advanced lytic bone lesions (scale 3)
• High M-component production rate - IgG value >7 g/dL; IgA value>5 g/dL; Bence Jones protein >12 g/24 h

The Eastern Cooperative Oncology Group (ECOG) Performance Status Score

• 0: Asymptomatic (Fully active, no restrictions in self care)
• 1: Symptomatic but completely ambulatory (Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature)
• 2: Symptomatic, <50% time in bed during the day (Ambulatory and capable of all self care but unable to carry out any work activities)
• 3: Symptomatic, >50% time in bed during waking hours (Capable of only limited self-care)
• 4: Bedbound (Completely disabled. Cannot carry on any self-care)
• 5: Death

Cytogenetics risk is determined by doing a genetic analysis of the participants bone marrow. The participants chromosomes are assessed for things like translocations (rearrangement of non-homologous chromosomes) or deletions (part of the genetic sequence is lost). Participants were considered high-risk if they had certain specific genetic changes. Translocations are noted as t(chromosome 1; chromosome 2) where the two chromosomes represent which non homologous chromosomes swapped genetic material. The high-risk cytogenetics included a deletion on chromosome 17, t(4;14), t(14;16), and t(14;20).

The serum heavy/light chain immunoassay quantifies the light chain types of each immunoglobulin (Ig) class based on a sample of the participants blood. Typical antibodies consist of two Ig heavy chains connected to two Ig light chains. When the plasma cells become cancerous, it can result in an increase in monoclonal immunoglobulin in the blood serum. This is used as a measure of the tumor load. The information below gives which specific monoclonal immunoglobulin was detected.

A summary of the number of participants with grade 3 or higher treatment related adverse events for adverse events that had an overall incidence of greater than 15% (any grade) as assessed by Common Terminology Criteria for Adverse Events (CTCAE 4).

The median amount of time as measured from the start of treatment until either death or progression.

Progressive disease requires 1 or more of the following:

• >=25% increase from lowest response level in serum M-protein (>=0.5 g/dL absolute increase) and/or urine M-component (>=200 mg/24hr absolute increase)
• >=25% increase in the difference between involved and uninvolved FLC levels (absolute increase >10 mg/dL). Only for use in patients without measurable serum and M-protein levels.
• >=25% increase in bone marrow plasma cell percentage (absolute percentage >=10%)
• New or increase in existing bone lesions or soft tissue plasmacytomas
• Hypercalcemia (serum calcium >11.5 mg/dL) due solely to the plasma cell proliferative disorder.

The median overall survival as measured from the start of treatment until the time of death due to any cause.

Median overall survival was not met before the end of follow-up/ data cutoff point because more than half of the participants were still alive.

Median amount of time from the start of treatment until first documented response as defined by the International Myeloma Working Group uniform response criteria

Stringent CR: Same as CR plus normal free light chain ratio and absence of clonal cells plasma cells in bone marrow (BM) CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and <5% plasma cells in BM VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level <100 mg per 24 hours PR: ≥50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ≥90% or to <200 mg per 24 hours. If the serum and urinary M-protein are not measurable, additional criteria are used to assess PR that will not fit in the space provided here. If present at baseline, a ≥50% reduction in the size of plasmacytomas is also required

Participants that achieved a response

Response rate was assessed using the International Myeloma Working Group uniform response criteria. Stringent complete response, Complete Response, Very Good Partial Response, and Partial Response are defined in outcome measure 1.

• MR included participants in whom some, but not all, criteria for PR were fulfilled, providing the remaining criteria satisfied the requirements for MR. Required all of the following:

  • ≥25% to ≤ 49% reduction in the level of serum monoclonal protein for at least two determinations six weeks apart.
  • If present, a 50 to 89% reduction in 24-hour light chain excretion, which still exceeds 200 mg/24 h, for at least two determinations six weeks apart.
  • 25-49% reduction in the size of plasmacytomas (by clinical or radiographic examination) for at least six weeks.
  • No increase in size or number of lytic bone lesions (development of compression fracture does not exclude response).

• Stable Disease: Not meeting the criteria for minimal response or

The pharmacokinetic profile of intravenous and subcutaneous bortezomib administration in combination with lenalidomide and dexamethasone.

A total of only 10 participants per arm were evaluated for drug plasma concentrations following Bortezomib administration.The number of participants vary by time-point due to missing measurements for the concentrations.

To evaluate pharmacogenomic markers among patients with treatment related polyneuropathy.

No pharmacogenomic markers were evaluated for relation to neuropathy