Study of Elotuzumab in Combination With Lenalidomide and Dexamethasone in Subjects With Multiple Myeloma and Various Levels of Renal Function

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01393964
• Collaborator: AbbVie (Industry)
• Enrollment: 35
• Locations: 11
• Arms: 3
• Actual Duration (Months): 54.4
• Patients Per Site: 3.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of the study is to assess the concentration of Elotuzumab in Myeloma patients with very low kidney function including patients on dialysis.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Lenalidomide; Drug: Dexamethasone; Drug: Dexamethasone; Drug: Dexamethasone; Biological: Elotuzumab (BMS-901608; HuLuc63)	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 35 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: PH Ib Study of Elotuzumab in Combination With Lenalidomide and Dexamethasone in Subjects With Multiple Myeloma and Normal Renal Function, Severe Renal Impairment, or End Stage Renal Disease Requiring Dialysis
• Actual Study Start Date: Jan 6, 2012
• Actual Primary Completion Date: Mar 21, 2014
• Actual Study Completion Date: Jul 18, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1: Lenalidomide + Dexamethasone +Elotuzumab Severe Renal Impairment	Drug: Lenalidomide; Capsules, Oral, 15 mg, One capsule every 48 hours through Days 1-21 (Repeat every 28 days until subject meets criteria for discontinuation of study drug; Other Names: Revlimid® ; Drug: Dexamethasone; Tablets, Oral, 28 mg weekly, on day 1 (cycle 1); days 1, 8, 15, 22 (cycles 2-3; days 1 &15 (cycle 4 and beyond) Repeat every 28 days until subject meets criteria for discontinuation of study drug; Other Names: Decadron® Dexamethasone Intensol® Dexpak® Taperpak® ; Drug: Dexamethasone; Tablets, Oral, 40 mg, weekly, on days 8, 15 & 22 (cycle 1); days 8 &22 (cycle 4 and beyond), Repeat every 28 days until subject meets criteria for discontinuation of study drug; Other Names: Decadron® Dexamethasone Intensol® Dexpak® Taperpak® ; Drug: Dexamethasone; Solution, Intravenous, 8 mg, weekly, on day 1 (cycle 1); days 1, 8, 15, 22 (cycles 2-3; days 1 &15 (cycle 4 and beyond) Repeat every 28 days until subject meets criteria for discontinuation of study drug; Other Names: Decadron® Dexamethasone Intensol® Dexpak® Taperpak® ; Biological: Elotuzumab (BMS-901608; HuLuc63); Solution, Intravenous, 10 mg/kg, weekly, on day 1 (cycle 1); days 1, 8, 15, 22 (cycles 2-3; days 1 &15 (cycle 4 and beyond), Repeat every 28 days until subject meets criteria for discontinuation of study drug
Experimental: Arm 2: Lenalidomide + Dexamethasone +Elotuzumab End-stage renal disease	Drug: Lenalidomide; Capsules, Oral, 15 mg, One capsule every 48 hours through Days 1-21 (Repeat every 28 days until subject meets criteria for discontinuation of study drug; Other Names: Revlimid® ; Drug: Dexamethasone; Tablets, Oral, 28 mg weekly, on day 1 (cycle 1); days 1, 8, 15, 22 (cycles 2-3; days 1 &15 (cycle 4 and beyond) Repeat every 28 days until subject meets criteria for discontinuation of study drug; Other Names: Decadron® Dexamethasone Intensol® Dexpak® Taperpak® ; Drug: Dexamethasone; Tablets, Oral, 40 mg, weekly, on days 8, 15 & 22 (cycle 1); days 8 &22 (cycle 4 and beyond), Repeat every 28 days until subject meets criteria for discontinuation of study drug; Other Names: Decadron® Dexamethasone Intensol® Dexpak® Taperpak® ; Drug: Dexamethasone; Solution, Intravenous, 8 mg, weekly, on day 1 (cycle 1); days 1, 8, 15, 22 (cycles 2-3; days 1 &15 (cycle 4 and beyond) Repeat every 28 days until subject meets criteria for discontinuation of study drug; Other Names: Decadron® Dexamethasone Intensol® Dexpak® Taperpak® ; Biological: Elotuzumab (BMS-901608; HuLuc63); Solution, Intravenous, 10 mg/kg, weekly, on day 1 (cycle 1); days 1, 8, 15, 22 (cycles 2-3; days 1 &15 (cycle 4 and beyond), Repeat every 28 days until subject meets criteria for discontinuation of study drug
Experimental: Arm 3: Lenalidomide + Dexamethasone +Elotuzumab Normal renal function	Drug: Lenalidomide; Capsules, Oral, 15 mg, One capsule every 48 hours through Days 1-21 (Repeat every 28 days until subject meets criteria for discontinuation of study drug; Other Names: Revlimid® ; Drug: Dexamethasone; Tablets, Oral, 28 mg weekly, on day 1 (cycle 1); days 1, 8, 15, 22 (cycles 2-3; days 1 &15 (cycle 4 and beyond) Repeat every 28 days until subject meets criteria for discontinuation of study drug; Other Names: Decadron® Dexamethasone Intensol® Dexpak® Taperpak® ; Drug: Dexamethasone; Tablets, Oral, 40 mg, weekly, on days 8, 15 & 22 (cycle 1); days 8 &22 (cycle 4 and beyond), Repeat every 28 days until subject meets criteria for discontinuation of study drug; Other Names: Decadron® Dexamethasone Intensol® Dexpak® Taperpak® ; Drug: Dexamethasone; Solution, Intravenous, 8 mg, weekly, on day 1 (cycle 1); days 1, 8, 15, 22 (cycles 2-3; days 1 &15 (cycle 4 and beyond) Repeat every 28 days until subject meets criteria for discontinuation of study drug; Other Names: Decadron® Dexamethasone Intensol® Dexpak® Taperpak® ; Biological: Elotuzumab (BMS-901608; HuLuc63); Solution, Intravenous, 10 mg/kg, weekly, on day 1 (cycle 1); days 1, 8, 15, 22 (cycles 2-3; days 1 &15 (cycle 4 and beyond), Repeat every 28 days until subject meets criteria for discontinuation of study drug

Outcome Measures

Primary Outcome Measures

1. Geometric Mean Maximum Observed Serum Concentration (Cmax) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method [Day 1 of Cycle 1 to 28 days post dose]

   The quantification of elotuzumab in human serum was performed using a validated Enzyme-linked immunoassay (ELISA). Cycle 1, day 1 sample times for all participants: 0 hour (h) pre-dose, end of infusion, 30 minutes (min) post end of infusion, 2 h, 4 h , and 24 h post end of infusion. Trough samples were obtained in subsequent cycles and at 30 day and 60 day follow-up visits at end of treatment. ESRD had 2 additional samples: immediately prior to and immediately after dialysis. Cmax was measured in micrograms per milliliter (µg/mL). Pharmacokinetic (PK) parameter renal function group assignment criteria differed slightly from the criteria for safety and efficacy analyses (specifically for the SRI group). PK criteria: All participants with at least one pretreatment value ≥ 90 mL/min were assigned to the NRF group. All those with at least one pretreatment value < 30 mL/min were assigned to the SRI group. All those with a screening diagnosis of ESRD, were assigned to the ESRD group.

2. Geometric Mean Area Under Serum Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration AUC(0-T) and From Time Zero Extrapolated to Infinite Time AUC(INF) of Elotuzumab Following Cycle 1, Day 1 - Grouping by C-G CrCl Method [Day 1 of Cycle 1 to 28 days post dose]

   The quantification of elotuzumab in human serum was performed using validated ELISA. Cycle 1, day 1 sample times for all participants: 0 hour (h) pre-dose, end of infusion, 30 minutes (min) post end of infusion, 2 h, 4 h , and 24 h post end of infusion. Trough samples were obtained in subsequent cycles and at 30 day and 60 day follow-up visits at end of treatment. ESRD participants had 2 additional sample times: immediately prior to and immediately after dialysis. AUC was measured in µg*h/mL. PK parameter renal function group assignment criteria differed slightly from the criteria for safety and efficacy analyses (specifically for the SRI group). PK criteria: All participants with at least one pretreatment value ≥ 90 mL/min were assigned to the NRF group. All those with at least one pretreatment value < 30 mL/min were assigned to the SRI group. All those with a screening diagnosis of ESRD, were assigned to the ESRD group

Secondary Outcome Measures

1. Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Who Died [From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)]

   AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.

2. Number of Participants With Persistent Elotuzumab Anti-drug Antibodies (ADA) and Number of Participants ADA Positive at Cycle 2 Pre-dose. [From first dose (Day 1) to last dose plus 60 days, up to Primary Endpoint (June 2014), approximately 2 years]

   Serum samples were evaluated for the presence of ADAs using a validated bridging electrochemiluminescence (ECL) immunoassay. Samples in: Cycle 1, Day 1 0 h (pre-dose), Cycle 2, Day 1(Study Day 29), 0 h (pre-dose; 672 h post-dose), Cycle 3, Day 1, 0 h and in cycle thereafter, at end of study/discontinuation, and at 30 and 60 day follow up visits post treatment. ADA Positive Participant: baseline negative with at least one ADA positive sample at any time after initiation of treatment or baseline positive with at least one ADA positive sample at any time after initiation of treatment with a titer 9-fold greater than the baseline; Persistent Positive: ADA positive at 2 or more sequential timepoints at least 12 weeks apart; Last Sample Positive: Not persistent positive and ADA Positive Sample in the last sampling timepoint; Other Positive: not persistent positive with ADA negative sample in the last sampling; ADA Negative: no ADA positive sample after the initiation of treatment.

3. Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests [From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)]

   National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 was used to measure toxicity scale. Lower Limits of Normal (LLN). Hemoglobin Gr 1:<LLN to 10.0 g/dL, Gr 2:<10.0 to 8.0 g/dL, Gr 3:<8.0 to 6.5 g/dL, Gr 4:<6.5 g/dL. Lymphocytes absolute (abs) Gr 1: <1.5 to 0.8 *10^3 c/µL, Gr 2 <0.8 to 0.5 *10^3 c/µL, Gr 3: <0.5 to 0.2 *10^3 c/µL, Gr 4: <0.2*10^3 c/µL. Neutrophils abs: Gr 1:<LLN to 1.5*10^9/L, Gr 2:<1.5 to 1.0*10^9/L, Gr 3:<1.0 to 0.5*10^9/L, Gr 4:<0.5*10^9/L. Platelet count Gr 1:LLN to 75.0*10^9/L, Gr 2:<75.0 to 50.0*10^9/L, Gr 3:<50.0 to 25.0*10^9/L, Gr 4:<25.0 to 10^9/L. Leukocytes Gr 1:<LLN to 3.0 *10^3 c/µL, Gr 2; <3.0 to 2.0 *10^3 c/µL, Gr 3: <2.0 to 1.0 *10^3 c/µL, Gr 4: <1.0 *10^3 c/µL.

4. Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests [From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)]

   NCI CTCAE, version 3.0 was used to measure toxicity scale. Lower Limits of Normal (LLN). Upper Limits of Normal (ULN). Alanine transaminase (ALT); Aspartate aminotransferase (AST); Alkaline phosphatase (ALP). ALT Grade (Gr)1:>1.0 to 2.5*ULN; Gr 2: >2.5 to 5.0*ULN; Gr 3: >5.0 to 20.0*ULN; Gr 4: >20.0*ULN. AST Gr 1: >1.0 to 2.5*ULN; Gr 2: >2.5 to 5.0*ULN; Gr 3: >5.0 to 20.0*ULN; Gr 4: >20.0*ULN. Total bilirubin Gr 1: >1.0 to 1.5*ULN; Gr 2: >1.5 to 3.0*ULN; Gr 3: >3.0 to 10..0*ULN; Gr 4: >10.0.0*ULN. ALP (U/L) Gr1:>1.0 to 2.5*ULN, Gr2:>2.5 to 5.0*ULN, Gr3:>5.0 to 20.0*ULN, Gr4:>20.0*ULN. Albumin (low) Gr 1:<LLN to 3 grams per deciliter (g/dL); Gr 2: <3.0 - 2.0 g/L; Gr 3: < 2 g/dL. Creatinine Gr 1: >1 - 1.5*baseline (BL)to >ULN - 1.5*ULN; Gr 2: >1.5 - 3.0*BL to > 1.5 - 3.0*ULN; Gr 3: >3.0*BL to > 3.0 - 6.0*ULN; Gr 4: >6.0*ULN.

5. Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests [From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)]

   Sodium high (H) Gr 1:>ULN - 150; Gr 2: >150 - 155; Gr 3: >155 - 160; Gr 4: >160 mmol/L; Sodium low(L) Gr 1:<LLN - 130; Gr 3: <130 - 120; Gr 4: <120 mmol/L. Potassium (H) Gr 1: >ULN - 5.5; Gr 2: >5.5 - 6.0; Gr 3: > 6.0 - 7.0; Gr 4: >7.0 mmol/L; Potassium (L) Gr 1: <LLN - 3.0; Gr 2: <LLN - 3.0; Gr 3: < 3.0 - 2.5; Gr 4: <2.5 mmol/L. Bicarbonate Gr1: 16-<LLN, Gr2: 11-16, Gr3, 8-11, Gr4: <8 milliequivalents per liter (mEq/L). Phosphorus Gr 1: 2.5 - <LLN, Gr2 2.0-<2.5, Gr3: 1.0-<2.0, Gr4: <1.0. Calcium (L) Gr 1: <LLN to 8.0; Gr2: 7.0 - 8.0; Gr3: 6.0-7.0; Gr 4: <6.0 mg/dL; calcium (H) Gr1:>ULN - 11.5, Gr2:>11.5 - 12.5, Gr3: 12.5 - 13.5, Gr4: >13.5.

Other Outcome Measures

1. Mean Terminal-phase Elimination Half-life (T-Half) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method [Day 1 of Cycle 1 to 28 days post dose]

   The quantification of elotuzumab in human serum was performed using validated ELISA. Cycle 1, day 1 sample times: 0 hour (h) pre-dose, end of infusion, 30 minutes (min) post end of infusion, 2 h, 4 h , and 24 h post end of infusion. Trough samples were obtained in subsequent cycles and at 30 day and 60 day follow-up visits at end of treatment. ESRD had 2 additional samples: immediately prior to and immediately after dialysis. T-Half was measured in hours (h). PK parameter renal function group assignment criteria differed slightly from the criteria for safety and efficacy analyses (specifically for the SRI group). PK criteria: All participants with at least one pretreatment value ≥ 90 mL/min were assigned to the NRF group. All those with at least one pretreatment value < 30 mL/min were assigned to the SRI group. All those with a screening diagnosis of ESRD, were assigned to the ESRD group.

2. Median Time to Maximal Concentration (Tmax) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method [Day 1 of Cycle 1 to 28 days post dose]

   The quantification of elotuzumab in human serum was performed using validated ELISA. Cycle 1, day 1 sample times for all participants: 0 hour (h) pre-dose, end of infusion, 30 minutes (min) post end of infusion, 2 h, 4 h , and 24 h post end of infusion. Trough samples were obtained in subsequent cycles and at 30 day and 60 day follow-up visits at end of treatment. ESRD had 2 additional samples: immediately prior to and immediately after dialysis. Tmax was measured in hours (h). PK parameter renal function group assignment criteria differed slightly from the criteria for safety and efficacy analyses (specifically for the SRI group). PK criteria: All participants with at least one pretreatment value ≥ 90 mL/min were assigned to the NRF group. All those with at least one pretreatment value < 30 mL/min were assigned to the SRI group. All those with a screening diagnosis of ESRD, were assigned to the ESRD group.

3. Geometric Mean Total Body Clearance (CLT) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method [Day 1 of Cycle 1 to 28 days post dose]

   The quantification of elotuzumab in human serum was performed using validated ELISA. Cycle 1, day 1 sample times for all participants: 0 hour (h) pre-dose, end of infusion, 30 minutes (min) post end of infusion, 2 h, 4 h , and 24 h post end of infusion. Trough samples were obtained in subsequent cycles and at 30 day and 60 day follow-up visits at end of treatment. ESRD had 2 additional samples: immediately prior to and immediately after dialysis. CLT was measured in mL per hour per kilogram body weight (mL/h/kg). PK parameter renal function group assignment criteria differed slightly from the criteria for safety and efficacy analyses (specifically for the SRI group). PK criteria: All participants with at least one pretreatment value ≥ 90 mL/min were assigned to the NRF group. All those with at least one pretreatment value < 30 mL/min were assigned to the SRI group. All those with a screening diagnosis of ESRD, were assigned to the ESRD group.

4. Geometric Mean Apparent Volume of Distribution (Vz) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method [Day 1 of Cycle 1 to 28 days post dose]

   The quantification of elotuzumab in human serum was performed using validated ELISA. Cycle 1, day 1 sample times for all participants: 0 hour (h) pre-dose, end of infusion, 30 minutes (min) post end of infusion, 2 h, 4 h , and 24 h post end of infusion. Trough samples were obtained in subsequent cycles and at 30 day and 60 day follow-up visits at end of treatment. ESRD had 2 additional samples: immediately prior to and immediately after dialysis. Vz was measured in mL per kilogram body weight (mL/kg). PK parameter renal function group assignment criteria differed slightly from the criteria for safety and efficacy analyses (specifically for the SRI group). PK criteria: All participants with at least one pretreatment value ≥ 90 mL/min were assigned to the NRF group. All those with at least one pretreatment value < 30 mL/min were assigned to the SRI group. All those with a screening diagnosis of ESRD, were assigned to the ESRD group.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects with Multiple Myeloma (MM) and renal function fitting one of three categories:

1. Severe renal impairment: estimated creatinine clearance (CrCl) <30 ml/min, but not requiring dialysis

2. End-stage renal disease: requiring hemodialysis

3. Normal renal function: estimated CrCl ≥90 ml/min

• Documented evidence of symptomatic MM, either newly diagnosed or relapsed/refractory

• Prior Lenalidomide exposure is permitted only if the subject did not discontinue Lenalidomide due to a Grade ≥3 related Adverse Event (AE)

Exclusion Criteria:

• Monoclonal Gammopathy of Undetermined Significance (MGUS), Waldenstrom's macroglobulinemia, or smoldering myeloma

• Active plasma cell leukemia

• All adverse events of any prior chemotherapy, surgery, or radiotherapy not resolved

• POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)

• Acute renal failure

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Winship Cancer Institute, Emory University	Atlanta	Georgia	United States	30322
2	Investigative Clinical Research Of Indiana, Llc	Indianapolis	Indiana	United States	46260
3	University Of Iowa Hospitals And Clinics	Iowa City	Iowa	United States	52242
4	University Of Maryland	Baltimore	Maryland	United States	21201
5	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
6	Washington University School Of Medicine	Saint Louis	Missouri	United States	63110
7	Weill Cornell Medical College	New York	New York	United States	10021
8	Mount Sinai Medical Center	New York	New York	United States	10029
9	Tennessee Oncology, Pllc	Nashville	Tennessee	United States	37203
10	The University Of Texas M.D. Anderson Cancer Center	Houston	Texas	United States	77030
11	Va Puget Sound Health Care System	Seattle	Washington	United States	98108

Sponsors and Collaborators

• Bristol-Myers Squibb
• AbbVie

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• BMS Clinical Trial Information
• BMS clinical trial educational resource
• FDA Safety Alerts and Recalls

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT01393964
• Other Study ID Numbers: CA204-007
• First Posted: Jul 14, 2011
• Last Update Posted: Aug 3, 2017
• Last Verified: Jun 1, 2017

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Dexamethasone; Dexamethasone acetate; Lenalidomide; Elotuzumab; BB 1101

Study Results

Participant Flow

Pre-assignment Detail	35 participants were enrolled; 9 did not enter into the treatment period. Reasons for not entering treatment period: 8 no longer met criteria, 1 other.

Arm/Group Title	Elotuzumab + LD in Normal Renal Function(NRF) Participants	Elotuzumab + LD in Severe Renal Impairment(SRI) Participants	Elotuzumab + LD in End Stage Renal Disease(ESRD) Participants
Arm/Group Description	Combination of lenalidomide and dexamethasone (LD). Elotuzumab + LD were administered in 28 day cycles: Elotuzumab 10 mg/kg intravenous (IV) was administered on Day 1 only for Cycle 1, weekly (Days 1, 8, 15, 22) for Cycles 2 and 3, and every 2 weeks (Q2W) beginning with Cycle 4 and thereafter until disease progression, discontinuation due to unacceptable toxicity, or other protocol-specified reasons. Lenalidomide dosing was based on creatinine clearance (CrCl) calculated using the Cockcroft-Gault (C-G) formula based on Day 1 creatinine and Day 1 weight measured at each cycle (per product label). Dexamethasone was administered weekly as a 40mg oral dose (po) on weeks without elotuzumab; and as a split dose of 28 mg po 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G Creatinine Clearance CrCl Method was used to determine renal function. NRF = CrCl ≥ 90 milliliters per minute (mL/min).	Elotuzumab + LD were administered in 28 day cycles: Elotuzumab 10 mg/kg IV was administered on Day 1 only for Cycle 1, weekly for Cycles 2 and 3, and Q2W beginning with Cycle 4 and thereafter until disease progression, discontinuation due to unacceptable toxicity, or other protocol-specified reasons. Lenalidomide dosing was based on CrCl calculated using the C-G formula based on Day 1 creatinine and Day 1 weight measured at each cycle(per product label). Dexamethasone was administered weekly PO as 40mg dose on weeks without elotuzumab; and as a split dose of 28 mg PO 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G CrCl Method was used to determine renal function. SRI = estimated CrCl < 30 ml/min but no dialysis.	Elotuzumab + LD were administered in 28 day cycles: Elotuzumab 10 mg/kg intravenous (IV) was administered on Day 1 only for Cycle 1, weekly for Cycles 2 and 3, Q2W beginning with Cycle 4 and thereafter until disease progression, discontinuation due to unacceptable toxicity, or other protocol-specified reasons. Lenalidomide dosing was based on CrCl calculated using the C-G formula based on Day 1 creatinine and Day 1 weight measured at each cycle(per product label). Dexamethasone was administered weekly as a 40mg PO dose on weeks without elotuzumab; and as a split dose of 28 mg PO 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G CrCl Method was used to determine renal function. ESRD = requires hemodialysis.
Period Title: Overall Study
STARTED	8	9	9
COMPLETED	0	0	0
NOT COMPLETED	8	9	9

Baseline Characteristics

Arm/Group Title	Elotuzumab + LD in Normal Renal Function (NRF) Participants	Elotuzumab + LD in Severe Renal Impairment (SRI) Participants	Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants	Total
Arm/Group Description	Treatment was administered in 28 day cycles: Elotuzumab 10 mg/kg intravenous (IV) was administered on Day 1 only for Cycle 1, weekly for Cycles 2 and 3, and every 2 weeks (Q2W) beginning with Cycle 4 and thereafter. Lenalidomide dosing was based on creatinine clearance (CrCl) calculated using the Cockcroft-Gault (C-G) formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly as a 40mg oral dose (po) on weeks without elotuzumab; and as a split dose of 28 mg po 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G Creatinine Clearance CrCl Method was used to determine renal function. NRF =CrCl ≥ 90 milliliters per minute (mL/min).	Treatment was administered in 28 day cycles: Elotuzumab 10 mg/kg IV was administered on Day 1 only for Cycle 1, weekly for Cycles 2 and 3, and Q2W beginning with Cycle 4 and thereafter. Lenalidomide dosing was based on CrCl calculated using the C-G formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly PO as 40mg dose on weeks without elotuzumab; and as a split dose of 28 mg PO 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G CrCl Method was used to determine renal function. SRI= estimated CrCl < 30 ml/min but no dialysis.	Treatment was administered in 28 day cycles: Elotuzumab 10 mg/kg intravenous (IV) was administered on Day 1 only for Cycle 1, weekly for Cycles 2 and 3, Q2W beginning with Cycle 4 and thereafter. Lenalidomide dosing was based on CrCl calculated using the C-G formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly as a 40mg PO dose on weeks without elotuzumab; and as a split dose of 28 mg PO 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G CrCl Method was used to determine renal function. ESRD= requires hemodialysis.	Total of all reporting groups
Overall Participants	8	9	9	26
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.8 (8.05)	75.9 (7.70)	55.6 (11.70)	63.3 (13.02)
Age, Customized (participants) [Number]
< 65 years	7 87.5%	1 11.1%	8 88.9%	16 61.5%
>=65 and < 75 years	1 12.5%	3 33.3%	0 0%	4 15.4%
>= 75 years	0 0%	5 55.6%	1 11.1%	6 23.1%
Sex: Female, Male (Count of Participants)
Female	3 37.5%	3 33.3%	4 44.4%	10 38.5%
Male	5 62.5%	6 66.7%	5 55.6%	16 61.5%
Region of Enrollment (participants) [Number]
United States	8 100%	9 100%	9 100%	26 100%

Outcome Measures

1. Primary Outcome

Title	Geometric Mean Maximum Observed Serum Concentration (Cmax) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method
Description	The quantification of elotuzumab in human serum was performed using a validated Enzyme-linked immunoassay (ELISA). Cycle 1, day 1 sample times for all participants: 0 hour (h) pre-dose, end of infusion, 30 minutes (min) post end of infusion, 2 h, 4 h , and 24 h post end of infusion. Trough samples were obtained in subsequent cycles and at 30 day and 60 day follow-up visits at end of treatment. ESRD had 2 additional samples: immediately prior to and immediately after dialysis. Cmax was measured in micrograms per milliliter (µg/mL). Pharmacokinetic (PK) parameter renal function group assignment criteria differed slightly from the criteria for safety and efficacy analyses (specifically for the SRI group). PK criteria: All participants with at least one pretreatment value ≥ 90 mL/min were assigned to the NRF group. All those with at least one pretreatment value < 30 mL/min were assigned to the SRI group. All those with a screening diagnosis of ESRD, were assigned to the ESRD group.
Time Frame	Day 1 of Cycle 1 to 28 days post dose

Outcome Measure Data

Analysis Population Description

The analyses of primary endpoint of PK parameters were conducted by renal functions as determined by CrCl C-G method in those participants who were treated with at least one dose of study drug and had evaluable pre- and post-treatment values.

Arm/Group Title	Elotuzumab + LD in Normal Renal Function (NRF) Participants	Elotuzumab + LD in Severe Renal Impairment (SRI) Participants	Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants
Arm/Group Description	LD=Combination of lenalidomide and dexamethasone. Elotuzumab + LD were administered in 28 day cycles: Elotuzumab 10 mg/kg intravenous (IV) was administered on Day 1 only for Cycle 1, weekly for Cycles 2 and 3, and every 2 weeks (Q2W) beginning with Cycle 4 and thereafter. Lenalidomide dosing was based on creatinine clearance (CrCl) calculated using the Cockcroft-Gault (C-G) formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly as a 40mg oral dose (po) on weeks without elotuzumab; and as a split dose of 28 mg po 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G Creatinine Clearance CrCl Method was used to determine renal function. NRF =CrCl ≥ 90 milliliters per minute (mL/min).	Elotuzumab + LD were administered in 28 day cycles: Elotuzumab 10 mg/kg IV was administered on Day 1 only for Cycle 1, weekly for Cycles 2 and 3, and Q2W beginning with Cycle 4 and thereafter. Lenalidomide dosing was based on CrCl calculated using the C-G formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly PO as 40mg dose on weeks without elotuzumab; and as a split dose of 28 mg PO 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G CrCl Method was used to determine renal function. SRI= estimated CrCl < 30 ml/min but no dialysis.	Elotuzumab + LD were administered in 28 day cycles: Elotuzumab 10 mg/kg intravenous (IV) was administered on Day 1 only for Cycle 1, weekly for Cycles 2 and 3, Q2W beginning with Cycle 4 and thereafter. Lenalidomide dosing was based on CrCl calculated using the C-G formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly as a 40mg PO dose on weeks without elotuzumab; and as a split dose of 28 mg PO 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G CrCl Method was used to determine renal function. ESRD= requires hemodialysis.
Measure Participants	8	7	8
Geometric Mean (Geometric Coefficient of Variation) [µg/mL]	217 (24)	226 (10)	218 (21)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Elotuzumab + LD in Normal Renal Function (NRF) Participants, Elotuzumab + LD in Severe Renal Impairment (SRI) Participants
	Comments	The reference arm is NRF participants.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.704
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Ratio of Adjusted Means
	Estimated Value	104.096
	Confidence Interval	(2-Sided) 90%; 86.983 to 124.576
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Elotuzumab + LD in Normal Renal Function (NRF) Participants, Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants
	Comments	The reference arm is NRF participants.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.965
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	ratio of adjusted means
	Estimated Value	100.454
	Confidence Interval	(2-Sided) 90%; 84.453 to 119.488
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Geometric Mean Area Under Serum Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration AUC(0-T) and From Time Zero Extrapolated to Infinite Time AUC(INF) of Elotuzumab Following Cycle 1, Day 1 - Grouping by C-G CrCl Method
Description	The quantification of elotuzumab in human serum was performed using validated ELISA. Cycle 1, day 1 sample times for all participants: 0 hour (h) pre-dose, end of infusion, 30 minutes (min) post end of infusion, 2 h, 4 h , and 24 h post end of infusion. Trough samples were obtained in subsequent cycles and at 30 day and 60 day follow-up visits at end of treatment. ESRD participants had 2 additional sample times: immediately prior to and immediately after dialysis. AUC was measured in µg*h/mL. PK parameter renal function group assignment criteria differed slightly from the criteria for safety and efficacy analyses (specifically for the SRI group). PK criteria: All participants with at least one pretreatment value ≥ 90 mL/min were assigned to the NRF group. All those with at least one pretreatment value < 30 mL/min were assigned to the SRI group. All those with a screening diagnosis of ESRD, were assigned to the ESRD group
Time Frame	Day 1 of Cycle 1 to 28 days post dose

Outcome Measure Data

Analysis Population Description

The analyses of primary endpoint of PK parameters were conducted by renal functions as determined by CrCl C-G method in those participants who were treated with at least one dose of study drug and had evaluable pre- and post-treatment values.

Arm/Group Title	Elotuzumab + LD in Normal Renal Function (NRF) Participants	Elotuzumab + LD in Severe Renal Impairment (SRI) Participants	Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants
Arm/Group Description	LD=Combination of lenalidomide and dexamethasone. Treatment was administered in 28 day cycles: Elotuzumab 10 mg/kg intravenous (IV) was administered on Day 1 only for Cycle 1, weekly for Cycles 2 and 3, and every 2 weeks (Q2W) beginning with Cycle 4 and thereafter. Lenalidomide dosing was based on creatinine clearance (CrCl) calculated using the Cockcroft-Gault (C-G) formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly as a 40mg oral dose (po) on weeks without elotuzumab; and as a split dose of 28 mg po 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G Creatinine Clearance CrCl Method was used to determine renal function. NRF =CrCl ≥ 90 milliliters per minute (mL/min).	Treatment was administered in 28 day cycles: Elotuzumab 10 mg/kg IV was administered on Day 1 only for Cycle 1, weekly for Cycles 2 and 3, and Q2W beginning with Cycle 4 and thereafter. Lenalidomide dosing was based on CrCl calculated using the C-G formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly PO as 40mg dose on weeks without elotuzumab; and as a split dose of 28 mg PO 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G CrCl Method was used to determine renal function. SRI= estimated CrCl < 30 ml/min but no dialysis.	Treatment was administered in 28 day cycles: Elotuzumab 10 mg/kg intravenous (IV) was administered on Day 1 only for Cycle 1, weekly for Cycles 2 and 3, Q2W beginning with Cycle 4 and thereafter. Lenalidomide dosing was based on CrCl calculated using the C-G formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly as a 40mg PO dose on weeks without elotuzumab; and as a split dose of 28 mg PO 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G CrCl Method was used to determine renal function. ESRD= requires hemodialysis.
Measure Participants	8	7	8
AUC (0-T)	39559 (28)	50080 (20)	45937 (31)
AUC (INF)	46401 (39)	60255 (31)	51227 (39)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Elotuzumab + LD in Normal Renal Function (NRF) Participants, Elotuzumab + LD in Severe Renal Impairment (SRI) Participants
	Comments	AUC(0-T). The reference arm is NRF participants.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.164
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Ratio of Adjusted Means
	Estimated Value	126.596
	Confidence Interval	(2-Sided) 90%; 95.52 to 167.783
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Elotuzumab + LD in Normal Renal Function (NRF) Participants, Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants
	Comments	AUC(0-T). The reference arm is NRF participants.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.355
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Ratio of Adjusted Means
	Estimated Value	116.123
	Confidence Interval	(2-Sided) 90%; 88.458 to 152.439
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Elotuzumab + LD in Normal Renal Function (NRF) Participants, Elotuzumab + LD in Severe Renal Impairment (SRI) Participants
	Comments	AUC (INF). The reference arm is NRF participants.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.228
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Ratio of Adjusted Means
	Estimated Value	129.858
	Confidence Interval	(2-Sided) 90%; 90.366 to 186.609
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Elotuzumab + LD in Normal Renal Function (NRF) Participants, Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants
	Comments	AUC(INF). The reference arm is NRF participants.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.642
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Ratio of Adjusted Means
	Estimated Value	110.400
	Confidence Interval	(2-Sided) 90%; 76.825 to 158.647
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Who Died
Description	AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
Time Frame	From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study treatment (at least one dose of any drug) were summarized.

Arm/Group Title	Elotuzumab + LD in Normal Renal Function (NRF) Participants	Elotuzumab + LD in Severe Renal Impairment (SRI) Participants	Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants
Arm/Group Description	LD=Combination of lenalidomide and dexamethasone. Elotuzumab + LD were administered in 28 day cycles: Elotuzumab 10 mg/kg intravenous (IV) was administered on Day 1 only for Cycle 1, weekly (Days 1, 8, 15, 22) for Cycles 2 and 3, and every 2 weeks (Q2W) beginning with Cycle 4 and thereafter until disease progression, discontinuation due to unacceptable toxicity, or other protocol-specified reasons. Lenalidomide dosing was based on creatinine clearance (CrCl) calculated using the Cockcroft-Gault (C-G) formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly as a 40mg oral dose (po) on weeks without elotuzumab; and as a split dose of 28 mg po 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G Creatinine Clearance CrCl Method was used to determine renal function. NRF =CrCl ≥ 90 milliliters per minute (mL/min).	Elotuzumab + LD were administered in 28 day cycles: Elotuzumab 10 mg/kg IV was administered on Day 1 only for Cycle 1, weekly for Cycles 2 and 3, and Q2W beginning with Cycle 4 and thereafter until disease progression, discontinuation due to unacceptable toxicity, or other protocol-specified reasons. Lenalidomide dosing was based on CrCl calculated using the C-G formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly PO as 40mg dose on weeks without elotuzumab; and as a split dose of 28 mg PO 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G CrCl Method was used to determine renal function. SRI= estimated CrCl < 30 ml/min but no dialysis.	Elotuzumab + LD were administered in 28 day cycles: Elotuzumab 10 mg/kg intravenous (IV) was administered on Day 1 only for Cycle 1, weekly for Cycles 2 and 3, Q2W beginning with Cycle 4 and thereafter until disease progression, discontinuation due to unacceptable toxicity, or other protocol-specified reasons. Lenalidomide dosing was based on CrCl calculated using the C-G formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly as a 40mg PO dose on weeks without elotuzumab; and as a split dose of 28 mg PO 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G CrCl Method was used to determine renal function. ESRD= requires hemodialysis.
Measure Participants	8	9	9
Deaths	0 0%	0 0%	0 0%
Any SAE	3 37.5%	5 55.6%	7 77.8%
AEs Leading to Discontinuation	1 12.5%	4 44.4%	1 11.1%

4. Secondary Outcome

Title	Number of Participants With Persistent Elotuzumab Anti-drug Antibodies (ADA) and Number of Participants ADA Positive at Cycle 2 Pre-dose.
Description	Serum samples were evaluated for the presence of ADAs using a validated bridging electrochemiluminescence (ECL) immunoassay. Samples in: Cycle 1, Day 1 0 h (pre-dose), Cycle 2, Day 1(Study Day 29), 0 h (pre-dose; 672 h post-dose), Cycle 3, Day 1, 0 h and in cycle thereafter, at end of study/discontinuation, and at 30 and 60 day follow up visits post treatment. ADA Positive Participant: baseline negative with at least one ADA positive sample at any time after initiation of treatment or baseline positive with at least one ADA positive sample at any time after initiation of treatment with a titer 9-fold greater than the baseline; Persistent Positive: ADA positive at 2 or more sequential timepoints at least 12 weeks apart; Last Sample Positive: Not persistent positive and ADA Positive Sample in the last sampling timepoint; Other Positive: not persistent positive with ADA negative sample in the last sampling; ADA Negative: no ADA positive sample after the initiation of treatment.
Time Frame	From first dose (Day 1) to last dose plus 60 days, up to Primary Endpoint (June 2014), approximately 2 years

Outcome Measure Data

Analysis Population Description

All participants with baseline ADA result and at least one on-treatment ADA result.

Arm/Group Title	Elotuzumab + LD in Normal Renal Function (NRF) Participants	Elotuzumab + LD in Severe Renal Impairment (SRI) Participants	Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants
Arm/Group Description	LD=Combination of lenalidomide and dexamethasone. Elotuzumab + LD were administered in 28 day cycles: Elotuzumab 10 mg/kg intravenous (IV) was administered on Day 1 only for Cycle 1, weekly (Days 1, 8, 15, 22) for Cycles 2 and 3, and every 2 weeks (Q2W) beginning with Cycle 4 and thereafter until disease progression, discontinuation due to unacceptable toxicity, or other protocol-specified reasons. Lenalidomide dosing was based on creatinine clearance (CrCl) calculated using the Cockcroft-Gault (C-G) formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly as a 40mg oral dose (po) on weeks without elotuzumab; and as a split dose of 28 mg po 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G Creatinine Clearance CrCl Method was used to determine renal function. NRF =CrCl ≥ 90 milliliters per minute (mL/min).	Elotuzumab + LD were administered in 28 day cycles: Elotuzumab 10 mg/kg IV was administered on Day 1 only for Cycle 1, weekly for Cycles 2 and 3, and Q2W beginning with Cycle 4 and thereafter until disease progression, discontinuation due to unacceptable toxicity, or other protocol-specified reasons. Lenalidomide dosing was based on CrCl calculated using the C-G formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly PO as 40mg dose on weeks without elotuzumab; and as a split dose of 28 mg PO 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G CrCl Method was used to determine renal function. SRI= estimated CrCl < 30 ml/min but no dialysis.	Elotuzumab + LD were administered in 28 day cycles: Elotuzumab 10 mg/kg intravenous (IV) was administered on Day 1 only for Cycle 1, weekly for Cycles 2 and 3, Q2W beginning with Cycle 4 and thereafter until disease progression, discontinuation due to unacceptable toxicity, or other protocol-specified reasons. Lenalidomide dosing was based on CrCl calculated using the C-G formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly as a 40mg PO dose on weeks without elotuzumab; and as a split dose of 28 mg PO 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G CrCl Method was used to determine renal function. ESRD= requires hemodialysis.
Measure Participants	6	4	6
Baseline ADA Positive	1 12.5%	0 0%	0 0%
On-Study ADA Positive	2 25%	1 11.1%	1 11.1%
Positive at Cycle 2 pre-dose	2 25%	0 0%	1 11.1%
Persistent Positive	0 0%	0 0%	0 0%
Last Sample Positive	1 12.5%	0 0%	1 11.1%
Other Positive	1 12.5%	1 11.1%	0 0%
On-Study ADA Negative	4 50%	3 33.3%	5 55.6%

5. Secondary Outcome

Title	Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests
Description	National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 was used to measure toxicity scale. Lower Limits of Normal (LLN). Hemoglobin Gr 1:<LLN to 10.0 g/dL, Gr 2:<10.0 to 8.0 g/dL, Gr 3:<8.0 to 6.5 g/dL, Gr 4:<6.5 g/dL. Lymphocytes absolute (abs) Gr 1: <1.5 to 0.8 *10^3 c/µL, Gr 2 <0.8 to 0.5 *10^3 c/µL, Gr 3: <0.5 to 0.2 *10^3 c/µL, Gr 4: <0.2*10^3 c/µL. Neutrophils abs: Gr 1:<LLN to 1.5*10^9/L, Gr 2:<1.5 to 1.0*10^9/L, Gr 3:<1.0 to 0.5*10^9/L, Gr 4:<0.5*10^9/L. Platelet count Gr 1:LLN to 75.0*10^9/L, Gr 2:<75.0 to 50.0*10^9/L, Gr 3:<50.0 to 25.0*10^9/L, Gr 4:<25.0 to 10^9/L. Leukocytes Gr 1:<LLN to 3.0 *10^3 c/µL, Gr 2; <3.0 to 2.0 *10^3 c/µL, Gr 3: <2.0 to 1.0 *10^3 c/µL, Gr 4: <1.0 *10^3 c/µL.
Time Frame	From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study treatment (at least one dose of any drug) were summarized.

Arm/Group Title	Elotuzumab + LD in Normal Renal Function (NRF) Participants	Elotuzumab + LD in Severe Renal Impairment (SRI) Participants	Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants
Arm/Group Description	LD=Combination of lenalidomide and dexamethasone. Elotuzumab + LD were administered in 28 day cycles: Elotuzumab 10 mg/kg intravenous (IV) was administered on Day 1 only for Cycle 1, weekly (Days 1, 8, 15, 22) for Cycles 2 and 3, and every 2 weeks (Q2W) beginning with Cycle 4 and thereafter until disease progression, discontinuation due to unacceptable toxicity, or other protocol-specified reasons. Lenalidomide dosing was based on creatinine clearance (CrCl) calculated using the Cockcroft-Gault (C-G) formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly as a 40mg oral dose (po) on weeks without elotuzumab; and as a split dose of 28 mg po 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G Creatinine Clearance CrCl Method was used to determine renal function. NRF =CrCl ≥ 90 milliliters per minute (mL/min).	Elotuzumab + LD were administered in 28 day cycles: Elotuzumab 10 mg/kg IV was administered on Day 1 only for Cycle 1, weekly for Cycles 2 and 3, and Q2W beginning with Cycle 4 and thereafter until disease progression, discontinuation due to unacceptable toxicity, or other protocol-specified reasons. Lenalidomide dosing was based on CrCl calculated using the C-G formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly PO as 40mg dose on weeks without elotuzumab; and as a split dose of 28 mg PO 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G CrCl Method was used to determine renal function. SRI= estimated CrCl < 30 ml/min but no dialysis.	Elotuzumab + LD were administered in 28 day cycles: Elotuzumab 10 mg/kg intravenous (IV) was administered on Day 1 only for Cycle 1, weekly for Cycles 2 and 3, Q2W beginning with Cycle 4 and thereafter until disease progression, discontinuation due to unacceptable toxicity, or other protocol-specified reasons. Lenalidomide dosing was based on CrCl calculated using the C-G formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly as a 40mg PO dose on weeks without elotuzumab; and as a split dose of 28 mg PO 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G CrCl Method was used to determine renal function. ESRD= requires hemodialysis.
Measure Participants	8	9	9
Hemoglobin Any Grade	8 100%	9 100%	9 100%
Hemoglobin Grade 3-4	0 0%	2 22.2%	6 66.7%
Platelet Count Any Grade	7 87.5%	8 88.9%	8 88.9%
Platelet Count Grade 3-4	0 0%	2 22.2%	2 22.2%
Leukocytes Any Grade	8 100%	8 88.9%	6 66.7%
Leukocytes Grade 3-4	3 37.5%	1 11.1%	2 22.2%
Lymphocytes (Abs) Any Grade	8 100%	9 100%	9 100%
Lymphocytes (Abs) Grade 3-4	6 75%	9 100%	5 55.6%
Neutrophil Count (Abs) Any Grade	6 75%	5 55.6%	6 66.7%
Neutrophil Count (Abs) Grade 3-4	3 37.5%	1 11.1%	2 22.2%

6. Secondary Outcome

Title	Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests
Description	NCI CTCAE, version 3.0 was used to measure toxicity scale. Lower Limits of Normal (LLN). Upper Limits of Normal (ULN). Alanine transaminase (ALT); Aspartate aminotransferase (AST); Alkaline phosphatase (ALP). ALT Grade (Gr)1:>1.0 to 2.5*ULN; Gr 2: >2.5 to 5.0*ULN; Gr 3: >5.0 to 20.0*ULN; Gr 4: >20.0*ULN. AST Gr 1: >1.0 to 2.5*ULN; Gr 2: >2.5 to 5.0*ULN; Gr 3: >5.0 to 20.0*ULN; Gr 4: >20.0*ULN. Total bilirubin Gr 1: >1.0 to 1.5*ULN; Gr 2: >1.5 to 3.0*ULN; Gr 3: >3.0 to 10..0*ULN; Gr 4: >10.0.0*ULN. ALP (U/L) Gr1:>1.0 to 2.5*ULN, Gr2:>2.5 to 5.0*ULN, Gr3:>5.0 to 20.0*ULN, Gr4:>20.0*ULN. Albumin (low) Gr 1:<LLN to 3 grams per deciliter (g/dL); Gr 2: <3.0 - 2.0 g/L; Gr 3: < 2 g/dL. Creatinine Gr 1: >1 - 1.5*baseline (BL)to >ULN - 1.5*ULN; Gr 2: >1.5 - 3.0*BL to > 1.5 - 3.0*ULN; Gr 3: >3.0*BL to > 3.0 - 6.0*ULN; Gr 4: >6.0*ULN.
Time Frame	From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study treatment (at least one dose of any drug) were summarized.

Arm/Group Title	Elotuzumab + LD in Normal Renal Function (NRF) Participants	Elotuzumab + LD in Severe Renal Impairment (SRI) Participants	Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants
Arm/Group Description	LD=Combination of lenalidomide and dexamethasone. Elotuzumab + LD were administered in 28 day cycles: Elotuzumab 10 mg/kg intravenous (IV) was administered on Day 1 only for Cycle 1, weekly (Days 1, 8, 15, 22) for Cycles 2 and 3, and every 2 weeks (Q2W) beginning with Cycle 4 and thereafter until disease progression, discontinuation due to unacceptable toxicity, or other protocol-specified reasons. Lenalidomide dosing was based on creatinine clearance (CrCl) calculated using the Cockcroft-Gault (C-G) formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly as a 40mg oral dose (po) on weeks without elotuzumab; and as a split dose of 28 mg po 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G Creatinine Clearance CrCl Method was used to determine renal function. NRF =CrCl ≥ 90 milliliters per minute (mL/min).	Elotuzumab + LD were administered in 28 day cycles: Elotuzumab 10 mg/kg IV was administered on Day 1 only for Cycle 1, weekly for Cycles 2 and 3, and Q2W beginning with Cycle 4 and thereafter until disease progression, discontinuation due to unacceptable toxicity, or other protocol-specified reasons. Lenalidomide dosing was based on CrCl calculated using the C-G formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly PO as 40mg dose on weeks without elotuzumab; and as a split dose of 28 mg PO 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G CrCl Method was used to determine renal function. SRI= estimated CrCl < 30 ml/min but no dialysis.	Elotuzumab + LD were administered in 28 day cycles: Elotuzumab 10 mg/kg intravenous (IV) was administered on Day 1 only for Cycle 1, weekly for Cycles 2 and 3, Q2W beginning with Cycle 4 and thereafter until disease progression, discontinuation due to unacceptable toxicity, or other protocol-specified reasons. Lenalidomide dosing was based on CrCl calculated using the C-G formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly as a 40mg PO dose on weeks without elotuzumab; and as a split dose of 28 mg PO 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G CrCl Method was used to determine renal function. ESRD= requires hemodialysis.
Measure Participants	8	9	9
ALP Any Grade	0 0%	3 33.3%	7 77.8%
ALP Grade 3-4	0 0%	0 0%	0 0%
AST Any Grade	3 37.5%	2 22.2%	5 55.6%
AST Grade 3-4	0 0%	0 0%	0 0%
ALT Any Grade	2 25%	5 55.6%	5 55.6%
ALT Grade 3-4	0 0%	0 0%	0 0%
Bilirubin Any Grade	1 12.5%	1 11.1%	2 22.2%
Bilirubin Grade 3-4	0 0%	0 0%	0 0%
Creatinine Any Grade	0 0%	9 100%	9 100%
Creatinine Grade 3-4	0 0%	2 22.2%	9 100%
Albumin Any Grade	2 25%	7 77.8%	7 77.8%
Albumin Grade 3-4	0 0%	0 0%	0 0%

7. Secondary Outcome

Title	Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests
Description	Sodium high (H) Gr 1:>ULN - 150; Gr 2: >150 - 155; Gr 3: >155 - 160; Gr 4: >160 mmol/L; Sodium low(L) Gr 1:<LLN - 130; Gr 3: <130 - 120; Gr 4: <120 mmol/L. Potassium (H) Gr 1: >ULN - 5.5; Gr 2: >5.5 - 6.0; Gr 3: > 6.0 - 7.0; Gr 4: >7.0 mmol/L; Potassium (L) Gr 1: <LLN - 3.0; Gr 2: <LLN - 3.0; Gr 3: < 3.0 - 2.5; Gr 4: <2.5 mmol/L. Bicarbonate Gr1: 16-<LLN, Gr2: 11-16, Gr3, 8-11, Gr4: <8 milliequivalents per liter (mEq/L). Phosphorus Gr 1: 2.5 - <LLN, Gr2 2.0-<2.5, Gr3: 1.0-<2.0, Gr4: <1.0. Calcium (L) Gr 1: <LLN to 8.0; Gr2: 7.0 - 8.0; Gr3: 6.0-7.0; Gr 4: <6.0 mg/dL; calcium (H) Gr1:>ULN - 11.5, Gr2:>11.5 - 12.5, Gr3: 12.5 - 13.5, Gr4: >13.5.
Time Frame	From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study treatment (at least one dose of any drug) were summarized.

Arm/Group Title	Elotuzumab + LD in Normal Renal Function (NRF) Participants	Elotuzumab + LD in Severe Renal Impairment (SRI) Participants	Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants
Arm/Group Description	LD=Combination of lenalidomide and dexamethasone. Elotuzumab + LD were administered in 28 day cycles: Elotuzumab 10 mg/kg intravenous (IV) was administered on Day 1 only for Cycle 1, weekly (Days 1, 8, 15, 22) for Cycles 2 and 3, and every 2 weeks (Q2W) beginning with Cycle 4 and thereafter until disease progression, discontinuation due to unacceptable toxicity, or other protocol-specified reasons. Lenalidomide dosing was based on creatinine clearance (CrCl) calculated using the Cockcroft-Gault (C-G) formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly as a 40mg oral dose (po) on weeks without elotuzumab; and as a split dose of 28 mg po 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G Creatinine Clearance CrCl Method was used to determine renal function. NRF =CrCl ≥ 90 milliliters per minute (mL/min).	Elotuzumab + LD were administered in 28 day cycles: Elotuzumab 10 mg/kg IV was administered on Day 1 only for Cycle 1, weekly for Cycles 2 and 3, and Q2W beginning with Cycle 4 and thereafter until disease progression, discontinuation due to unacceptable toxicity, or other protocol-specified reasons. Lenalidomide dosing was based on CrCl calculated using the C-G formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly PO as 40mg dose on weeks without elotuzumab; and as a split dose of 28 mg PO 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G CrCl Method was used to determine renal function. SRI= estimated CrCl < 30 ml/min but no dialysis.	Elotuzumab + LD were administered in 28 day cycles: Elotuzumab 10 mg/kg intravenous (IV) was administered on Day 1 only for Cycle 1, weekly for Cycles 2 and 3, Q2W beginning with Cycle 4 and thereafter until disease progression, discontinuation due to unacceptable toxicity, or other protocol-specified reasons. Lenalidomide dosing was based on CrCl calculated using the C-G formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly as a 40mg PO dose on weeks without elotuzumab; and as a split dose of 28 mg PO 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G CrCl Method was used to determine renal function. ESRD= requires hemodialysis.
Measure Participants	8	9	9
Sodium High Any Grade	2 25%	3 33.3%	2 22.2%
Sodium High Grade 3-4	0 0%	0 0%	0 0%
Sodium Low Any Grade	2 25%	6 66.7%	5 55.6%
Sodium Low Grade 3-4	1 12.5%	1 11.1%	0 0%
Potassium High Any Grade	2 25%	2 22.2%	4 44.4%
Potassium High Grade 3-4	0 0%	0 0%	3 33.3%
Potassium Low Any Grade	2 25%	5 55.6%	6 66.7%
Potassium Low Grade 3-4	0 0%	2 22.2%	1 11.1%
Bicarbonate Any Grade	5 62.5%	8 88.9%	6 66.7%
Bicarbonate Grade 3-4	0 0%	0 0%	0 0%
Calcium High Any Grade	1 12.5%	0 0%	3 33.3%
Calcium High Grade 3-4	0 0%	0 0%	1 11.1%
Calcium Low Any Grade	4 50%	6 66.7%	8 88.9%
Calcium Low Grade 3-4	0 0%	1 11.1%	2 22.2%
Glucose High Any Grade	7 87.5%	9 100%	7 77.8%
Glucose High Grade 3-4	3 37.5%	4 44.4%	3 33.3%
Glucose Low Any Grade	1 12.5%	0 0%	1 11.1%
Glucose Low Grade 3-4	0 0%	0 0%	0 0%

8. Other Pre-specified Outcome

Title	Mean Terminal-phase Elimination Half-life (T-Half) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method
Description	The quantification of elotuzumab in human serum was performed using validated ELISA. Cycle 1, day 1 sample times: 0 hour (h) pre-dose, end of infusion, 30 minutes (min) post end of infusion, 2 h, 4 h , and 24 h post end of infusion. Trough samples were obtained in subsequent cycles and at 30 day and 60 day follow-up visits at end of treatment. ESRD had 2 additional samples: immediately prior to and immediately after dialysis. T-Half was measured in hours (h). PK parameter renal function group assignment criteria differed slightly from the criteria for safety and efficacy analyses (specifically for the SRI group). PK criteria: All participants with at least one pretreatment value ≥ 90 mL/min were assigned to the NRF group. All those with at least one pretreatment value < 30 mL/min were assigned to the SRI group. All those with a screening diagnosis of ESRD, were assigned to the ESRD group.
Time Frame	Day 1 of Cycle 1 to 28 days post dose

Outcome Measure Data

Analysis Population Description

The analyses of PK parameters were conducted by renal functions as determined by CrCl C-G method in those participants who were treated with at least one dose of study drug and had evaluable pre- and post-treatment values.

Arm/Group Title	Elotuzumab + LD in Normal Renal Function (NRF) Participants	Elotuzumab + LD in Severe Renal Impairment (SRI) Participants	Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants
Arm/Group Description	LD=Combination of lenalidomide and dexamethasone. Elotuzumab + LD were administered in 28 day cycles: Elotuzumab 10 mg/kg intravenous (IV) was administered on Day 1 only for Cycle 1, weekly (Days 1, 8, 15, 22) for Cycles 2 and 3, and every 2 weeks (Q2W) beginning with Cycle 4 and thereafter until disease progression, discontinuation due to unacceptable toxicity, or other protocol-specified reasons. Lenalidomide dosing was based on creatinine clearance (CrCl) calculated using the Cockcroft-Gault (C-G) formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly as a 40mg oral dose (po) on weeks without elotuzumab; and as a split dose of 28 mg po 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G Creatinine Clearance CrCl Method was used to determine renal function. NRF =CrCl ≥ 90 milliliters per minute (mL/min).	Elotuzumab + LD were administered in 28 day cycles: Elotuzumab 10 mg/kg IV was administered on Day 1 only for Cycle 1, weekly for Cycles 2 and 3, and Q2W beginning with Cycle 4 and thereafter until disease progression, discontinuation due to unacceptable toxicity, or other protocol-specified reasons. Lenalidomide dosing was based on CrCl calculated using the C-G formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly PO as 40mg dose on weeks without elotuzumab; and as a split dose of 28 mg PO 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G CrCl Method was used to determine renal function. SRI= estimated CrCl < 30 ml/min but no dialysis.	Elotuzumab + LD were administered in 28 day cycles: Elotuzumab 10 mg/kg intravenous (IV) was administered on Day 1 only for Cycle 1, weekly for Cycles 2 and 3, Q2W beginning with Cycle 4 and thereafter until disease progression, discontinuation due to unacceptable toxicity, or other protocol-specified reasons. Lenalidomide dosing was based on CrCl calculated using the C-G formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly as a 40mg PO dose on weeks without elotuzumab; and as a split dose of 28 mg PO 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G CrCl Method was used to determine renal function. ESRD= requires hemodialysis.
Measure Participants	8	7	8
Mean (Standard Deviation) [h]	204 (134.11)	237 (107.88)	218 (98.87)

9. Other Pre-specified Outcome

Title	Median Time to Maximal Concentration (Tmax) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method
Description	The quantification of elotuzumab in human serum was performed using validated ELISA. Cycle 1, day 1 sample times for all participants: 0 hour (h) pre-dose, end of infusion, 30 minutes (min) post end of infusion, 2 h, 4 h , and 24 h post end of infusion. Trough samples were obtained in subsequent cycles and at 30 day and 60 day follow-up visits at end of treatment. ESRD had 2 additional samples: immediately prior to and immediately after dialysis. Tmax was measured in hours (h). PK parameter renal function group assignment criteria differed slightly from the criteria for safety and efficacy analyses (specifically for the SRI group). PK criteria: All participants with at least one pretreatment value ≥ 90 mL/min were assigned to the NRF group. All those with at least one pretreatment value < 30 mL/min were assigned to the SRI group. All those with a screening diagnosis of ESRD, were assigned to the ESRD group.
Time Frame	Day 1 of Cycle 1 to 28 days post dose

Outcome Measure Data

Analysis Population Description

The analyses of PK parameters were conducted by renal functions as determined by CrCl C-G method in those participants who were treated with at least one dose of study drug and had evaluable pre- and post-treatment values.

Arm/Group Title	Elotuzumab + LD in Normal Renal Function (NRF) Participants	Elotuzumab + LD in Severe Renal Impairment (SRI) Participants	Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants
Arm/Group Description	LD=Combination of lenalidomide and dexamethasone. Elotuzumab + LD were administered in 28 day cycles: Elotuzumab 10 mg/kg intravenous (IV) was administered on Day 1 only for Cycle 1, weekly (Days 1, 8, 15, 22) for Cycles 2 and 3, and every 2 weeks (Q2W) beginning with Cycle 4 and thereafter until disease progression, discontinuation due to unacceptable toxicity, or other protocol-specified reasons. Lenalidomide dosing was based on creatinine clearance (CrCl) calculated using the Cockcroft-Gault (C-G) formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly as a 40mg oral dose (po) on weeks without elotuzumab; and as a split dose of 28 mg po 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G Creatinine Clearance CrCl Method was used to determine renal function. NRF =CrCl ≥ 90 milliliters per minute (mL/min).	Elotuzumab + LD were administered in 28 day cycles: Elotuzumab 10 mg/kg IV was administered on Day 1 only for Cycle 1, weekly for Cycles 2 and 3, and Q2W beginning with Cycle 4 and thereafter until disease progression, discontinuation due to unacceptable toxicity, or other protocol-specified reasons. Lenalidomide dosing was based on CrCl calculated using the C-G formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly PO as 40mg dose on weeks without elotuzumab; and as a split dose of 28 mg PO 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G CrCl Method was used to determine renal function. SRI= estimated CrCl < 30 ml/min but no dialysis.	Elotuzumab + LD were administered in 28 day cycles: Elotuzumab 10 mg/kg intravenous (IV) was administered on Day 1 only for Cycle 1, weekly for Cycles 2 and 3, Q2W beginning with Cycle 4 and thereafter until disease progression, discontinuation due to unacceptable toxicity, or other protocol-specified reasons. Lenalidomide dosing was based on CrCl calculated using the C-G formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly as a 40mg PO dose on weeks without elotuzumab; and as a split dose of 28 mg PO 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G CrCl Method was used to determine renal function. ESRD= requires hemodialysis.
Measure Participants	8	7	8
Median (Full Range) [h]	3.23	3.87	3.33

10. Other Pre-specified Outcome

Title	Geometric Mean Total Body Clearance (CLT) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method
Description	The quantification of elotuzumab in human serum was performed using validated ELISA. Cycle 1, day 1 sample times for all participants: 0 hour (h) pre-dose, end of infusion, 30 minutes (min) post end of infusion, 2 h, 4 h , and 24 h post end of infusion. Trough samples were obtained in subsequent cycles and at 30 day and 60 day follow-up visits at end of treatment. ESRD had 2 additional samples: immediately prior to and immediately after dialysis. CLT was measured in mL per hour per kilogram body weight (mL/h/kg). PK parameter renal function group assignment criteria differed slightly from the criteria for safety and efficacy analyses (specifically for the SRI group). PK criteria: All participants with at least one pretreatment value ≥ 90 mL/min were assigned to the NRF group. All those with at least one pretreatment value < 30 mL/min were assigned to the SRI group. All those with a screening diagnosis of ESRD, were assigned to the ESRD group.
Time Frame	Day 1 of Cycle 1 to 28 days post dose

Outcome Measure Data

Analysis Population Description

The analyses of PK parameters were conducted by renal functions as determined by CrCl C-G method in those participants who were treated with at least one dose of study drug and had evaluable pre- and post-treatment values.

Arm/Group Title	Elotuzumab + LD in Normal Renal Function (NRF) Participants	Elotuzumab + LD in Severe Renal Impairment (SRI) Participants	Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants
Arm/Group Description	LD=Combination of lenalidomide and dexamethasone. Elotuzumab + LD were administered in 28 day cycles: Elotuzumab 10 mg/kg intravenous (IV) was administered on Day 1 only for Cycle 1, weekly (Days 1, 8, 15, 22) for Cycles 2 and 3, and every 2 weeks (Q2W) beginning with Cycle 4 and thereafter until disease progression, discontinuation due to unacceptable toxicity, or other protocol-specified reasons. Lenalidomide dosing was based on creatinine clearance (CrCl) calculated using the Cockcroft-Gault (C-G) formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly as a 40mg oral dose (po) on weeks without elotuzumab; and as a split dose of 28 mg po 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G Creatinine Clearance CrCl Method was used to determine renal function. NRF =CrCl ≥ 90 milliliters per minute (mL/min).	Elotuzumab + LD were administered in 28 day cycles: Elotuzumab 10 mg/kg IV was administered on Day 1 only for Cycle 1, weekly for Cycles 2 and 3, and Q2W beginning with Cycle 4 and thereafter until disease progression, discontinuation due to unacceptable toxicity, or other protocol-specified reasons. Lenalidomide dosing was based on CrCl calculated using the C-G formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly PO as 40mg dose on weeks without elotuzumab; and as a split dose of 28 mg PO 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G CrCl Method was used to determine renal function. SRI= estimated CrCl < 30 ml/min but no dialysis.	Elotuzumab + LD were administered in 28 day cycles: Elotuzumab 10 mg/kg intravenous (IV) was administered on Day 1 only for Cycle 1, weekly for Cycles 2 and 3, Q2W beginning with Cycle 4 and thereafter until disease progression, discontinuation due to unacceptable toxicity, or other protocol-specified reasons. Lenalidomide dosing was based on CrCl calculated using the C-G formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly as a 40mg PO dose on weeks without elotuzumab; and as a split dose of 28 mg PO 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G CrCl Method was used to determine renal function. ESRD= requires hemodialysis.
Measure Participants	8	7	8
Geometric Mean (Geometric Coefficient of Variation) [mL/h/kg]	0.215 (46)	0.166 (28)	0.195 (54)

11. Other Pre-specified Outcome

Title	Geometric Mean Apparent Volume of Distribution (Vz) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method
Description	The quantification of elotuzumab in human serum was performed using validated ELISA. Cycle 1, day 1 sample times for all participants: 0 hour (h) pre-dose, end of infusion, 30 minutes (min) post end of infusion, 2 h, 4 h , and 24 h post end of infusion. Trough samples were obtained in subsequent cycles and at 30 day and 60 day follow-up visits at end of treatment. ESRD had 2 additional samples: immediately prior to and immediately after dialysis. Vz was measured in mL per kilogram body weight (mL/kg). PK parameter renal function group assignment criteria differed slightly from the criteria for safety and efficacy analyses (specifically for the SRI group). PK criteria: All participants with at least one pretreatment value ≥ 90 mL/min were assigned to the NRF group. All those with at least one pretreatment value < 30 mL/min were assigned to the SRI group. All those with a screening diagnosis of ESRD, were assigned to the ESRD group.
Time Frame	Day 1 of Cycle 1 to 28 days post dose

Outcome Measure Data

Analysis Population Description

The analyses of PK parameters were conducted by renal functions as determined by CrCl C-G method in those participants who were treated with at least one dose of study drug and had evaluable pre- and post-treatment values.

Arm/Group Title	Elotuzumab + LD in Normal Renal Function (NRF) Participants	Elotuzumab + LD in Severe Renal Impairment (SRI) Participants	Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants
Arm/Group Description	LD=Combination of lenalidomide and dexamethasone. Elotuzumab + LD were administered in 28 day cycles: Elotuzumab 10 mg/kg intravenous (IV) was administered on Day 1 only for Cycle 1, weekly (Days 1, 8, 15, 22) for Cycles 2 and 3, and every 2 weeks (Q2W) beginning with Cycle 4 and thereafter until disease progression, discontinuation due to unacceptable toxicity, or other protocol-specified reasons. Lenalidomide dosing was based on creatinine clearance (CrCl) calculated using the Cockcroft-Gault (C-G) formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly as a 40mg oral dose (po) on weeks without elotuzumab; and as a split dose of 28 mg po 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G Creatinine Clearance CrCl Method was used to determine renal function. NRF =CrCl ≥ 90 milliliters per minute (mL/min).	Elotuzumab + LD were administered in 28 day cycles: Elotuzumab 10 mg/kg IV was administered on Day 1 only for Cycle 1, weekly for Cycles 2 and 3, and Q2W beginning with Cycle 4 and thereafter until disease progression, discontinuation due to unacceptable toxicity, or other protocol-specified reasons. Lenalidomide dosing was based on CrCl calculated using the C-G formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly PO as 40mg dose on weeks without elotuzumab; and as a split dose of 28 mg PO 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G CrCl Method was used to determine renal function. SRI= estimated CrCl < 30 ml/min but no dialysis.	Elotuzumab + LD were administered in 28 day cycles: Elotuzumab 10 mg/kg intravenous (IV) was administered on Day 1 only for Cycle 1, weekly for Cycles 2 and 3, Q2W beginning with Cycle 4 and thereafter until disease progression, discontinuation due to unacceptable toxicity, or other protocol-specified reasons. Lenalidomide dosing was based on CrCl calculated using the C-G formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly as a 40mg PO dose on weeks without elotuzumab; and as a split dose of 28 mg PO 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G CrCl Method was used to determine renal function. ESRD= requires hemodialysis.
Measure Participants	8	7	8
Geometric Mean (Geometric Coefficient of Variation) [mL/kg]	59.4 (30)	54.6 (20)	61.2 (43)

Adverse Events

Time Frame	From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
Arm/Group Title	Elotuzumab + LD in Normal Renal Function (NRF) Participants		Elotuzumab + LD in Severe Renal Impairment (SRI) Participants		Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants
Arm/Group Description	LD=Combination of lenalidomide and dexamethasone. Elotuzumab + LD were administered in 28 day cycles: Elotuzumab 10 mg/kg intravenous (IV) was administered on Day 1 only for Cycle 1, weekly for Cycles 2 and 3, and every 2 weeks (Q2W) beginning with Cycle 4 and thereafter. Lenalidomide dosing was based on creatinine clearance (CrCl) calculated using the Cockcroft-Gault (C-G) formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly as a 40mg oral dose (po) on weeks without elotuzumab; and as a split dose of 28 mg po 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G Creatinine Clearance CrCl Method was used to determine renal function. NRF =CrCl ≥ 90 milliliters per minute (mL/min).		Elotuzumab + LD were administered in 28 day cycles: Elotuzumab 10 mg/kg IV was administered on Day 1 only for Cycle 1, weekly for Cycles 2 and 3, and Q2W beginning with Cycle 4 and thereafter. Lenalidomide dosing was based on CrCl calculated using the C-G formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly PO as 40mg dose on weeks without elotuzumab; and as a split dose of 28 mg PO 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G CrCl Method was used to determine renal function. SRI= estimated CrCl < 30 ml/min but no dialysis.		Elotuzumab + LD were administered in 28 day cycles: Elotuzumab 10 mg/kg intravenous (IV) was administered on Day 1 only for Cycle 1, weekly for Cycles 2 and 3, Q2W beginning with Cycle 4 and thereafter. Lenalidomide dosing was based on CrCl calculated using the C-G formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly as a 40mg PO dose on weeks without elotuzumab; and as a split dose of 28 mg PO 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G CrCl Method was used to determine renal function. ESRD= requires hemodialysis.
All Cause Mortality
	Elotuzumab + LD in Normal Renal Function (NRF) Participants		Elotuzumab + LD in Severe Renal Impairment (SRI) Participants		Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Elotuzumab + LD in Normal Renal Function (NRF) Participants		Elotuzumab + LD in Severe Renal Impairment (SRI) Participants		Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/8 (37.5%)		5/9 (55.6%)		7/9 (77.8%)
Blood and lymphatic system disorders
Anaemia macrocytic	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Febrile neutropenia	0/8 (0%)		0/9 (0%)		2/9 (22.2%)
Cardiac disorders
Atrial fibrillation	0/8 (0%)		1/9 (11.1%)		1/9 (11.1%)
Bradycardia	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Tachycardia	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Endocrine disorders
Hypothyroidism	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Gastrointestinal disorders
Abdominal pain	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Diarrhoea	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
General disorders
Chest discomfort	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Chest pain	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Pyrexia	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Hepatobiliary disorders
Cholecystitis	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Infections and infestations
Bronchitis	0/8 (0%)		1/9 (11.1%)		1/9 (11.1%)
Clostridium difficile infection	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Gastroenteritis salmonella	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Influenza	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Meningitis bacterial	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Pneumonia	1/8 (12.5%)		0/9 (0%)		2/9 (22.2%)
Pneumonia respiratory syncytial viral	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Sepsis	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Soft tissue infection	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Staphylococcal bacteraemia	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Upper respiratory tract infection	0/8 (0%)		1/9 (11.1%)		1/9 (11.1%)
Investigations
Blood creatinine increased	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Influenza a virus test positive	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Metabolism and nutrition disorders
Gout	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Hypercalcaemia	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Hyperglycaemia	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Hyperkalaemia	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Hyperphosphataemia	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Dyspnoea	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Pulmonary embolism	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Vascular disorders
Deep vein thrombosis	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Hypertensive crisis	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Hypotension	0/8 (0%)		1/9 (11.1%)		1/9 (11.1%)
Other (Not Including Serious) Adverse Events
	Elotuzumab + LD in Normal Renal Function (NRF) Participants		Elotuzumab + LD in Severe Renal Impairment (SRI) Participants		Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/8 (100%)		9/9 (100%)		9/9 (100%)
Blood and lymphatic system disorders
Anaemia	4/8 (50%)		5/9 (55.6%)		3/9 (33.3%)
Febrile neutropenia	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Iron deficiency anaemia	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Leukocytosis	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Leukopenia	2/8 (25%)		1/9 (11.1%)		2/9 (22.2%)
Lymphopenia	2/8 (25%)		1/9 (11.1%)		2/9 (22.2%)
Neutropenia	3/8 (37.5%)		1/9 (11.1%)		1/9 (11.1%)
Thrombocytopenia	1/8 (12.5%)		4/9 (44.4%)		3/9 (33.3%)
Thrombocytosis	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Cardiac disorders
Atrial fibrillation	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Bradycardia	1/8 (12.5%)		0/9 (0%)		1/9 (11.1%)
Left ventricular dysfunction	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Sinus bradycardia	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Tachycardia	2/8 (25%)		0/9 (0%)		2/9 (22.2%)
Ear and labyrinth disorders
Ear pain	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Endocrine disorders
Cushingoid	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Hyperthyroidism	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Hypothyroidism	0/8 (0%)		0/9 (0%)		2/9 (22.2%)
Eye disorders
Cataract	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Dry eye	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Eye haemorrhage	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Lacrimation increased	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Macular fibrosis	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Ocular discomfort	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Periorbital oedema	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Scleral hyperaemia	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Vision blurred	2/8 (25%)		3/9 (33.3%)		1/9 (11.1%)
Visual impairment	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Gastrointestinal disorders
Abdominal distension	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Abdominal pain	0/8 (0%)		1/9 (11.1%)		2/9 (22.2%)
Abdominal pain lower	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Constipation	6/8 (75%)		3/9 (33.3%)		2/9 (22.2%)
Diarrhoea	3/8 (37.5%)		5/9 (55.6%)		5/9 (55.6%)
Diverticulum intestinal	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Dry mouth	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Dyspepsia	2/8 (25%)		3/9 (33.3%)		0/9 (0%)
Gastrooesophageal reflux disease	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Gingival bleeding	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Haemorrhoids	1/8 (12.5%)		1/9 (11.1%)		0/9 (0%)
Inguinal hernia	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Nausea	3/8 (37.5%)		2/9 (22.2%)		4/9 (44.4%)
Pancreatic cyst	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Rectal polyp	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Stomatitis	1/8 (12.5%)		4/9 (44.4%)		1/9 (11.1%)
Vomiting	1/8 (12.5%)		0/9 (0%)		4/9 (44.4%)
General disorders
Asthenia	1/8 (12.5%)		1/9 (11.1%)		2/9 (22.2%)
Catheter site haemorrhage	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Catheter site pain	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Chest discomfort	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Chest pain	1/8 (12.5%)		0/9 (0%)		1/9 (11.1%)
Chills	2/8 (25%)		0/9 (0%)		2/9 (22.2%)
Cyst	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Fatigue	6/8 (75%)		4/9 (44.4%)		7/9 (77.8%)
Feeling abnormal	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Gait disturbance	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Influenza like illness	2/8 (25%)		0/9 (0%)		0/9 (0%)
Infusion site bruising	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Injection site extravasation	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Local swelling	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Localised oedema	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Malaise	3/8 (37.5%)		1/9 (11.1%)		0/9 (0%)
Mucosal inflammation	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Non-cardiac chest pain	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Oedema	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Oedema peripheral	2/8 (25%)		4/9 (44.4%)		4/9 (44.4%)
Pain	0/8 (0%)		0/9 (0%)		2/9 (22.2%)
Peripheral swelling	0/8 (0%)		0/9 (0%)		2/9 (22.2%)
Pyrexia	4/8 (50%)		2/9 (22.2%)		4/9 (44.4%)
Immune system disorders
Hypersensitivity	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Infections and infestations
Abdominal hernia infection	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Atypical pneumonia	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Bacterial infection	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Bronchitis	0/8 (0%)		2/9 (22.2%)		1/9 (11.1%)
Cellulitis	1/8 (12.5%)		2/9 (22.2%)		0/9 (0%)
Clostridium difficile infection	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Conjunctivitis	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Endocarditis bacterial	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Fungal skin infection	1/8 (12.5%)		0/9 (0%)		1/9 (11.1%)
Gastroenteritis	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Gastroenteritis viral	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Herpes zoster	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Influenza	2/8 (25%)		0/9 (0%)		0/9 (0%)
Nasopharyngitis	0/8 (0%)		1/9 (11.1%)		2/9 (22.2%)
Parainfluenzae virus infection	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Pneumonia	2/8 (25%)		1/9 (11.1%)		0/9 (0%)
Postoperative wound infection	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Rash pustular	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Rhinitis	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Sinusitis	0/8 (0%)		2/9 (22.2%)		1/9 (11.1%)
Staphylococcal infection	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Trichomoniasis	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Upper respiratory tract infection	3/8 (37.5%)		3/9 (33.3%)		4/9 (44.4%)
Urinary tract infection	0/8 (0%)		3/9 (33.3%)		1/9 (11.1%)
Injury, poisoning and procedural complications
Accidental overdose	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Ankle fracture	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Contusion	0/8 (0%)		3/9 (33.3%)		2/9 (22.2%)
Fall	0/8 (0%)		1/9 (11.1%)		2/9 (22.2%)
Incision site pain	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Infusion related reaction	1/8 (12.5%)		0/9 (0%)		1/9 (11.1%)
Ligament sprain	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Sunburn	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Vascular access complication	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Wound	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Investigations
Alanine aminotransferase increased	1/8 (12.5%)		1/9 (11.1%)		2/9 (22.2%)
Aspartate aminotransferase decreased	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Aspartate aminotransferase increased	1/8 (12.5%)		0/9 (0%)		2/9 (22.2%)
Blood alkaline phosphatase increased	0/8 (0%)		1/9 (11.1%)		1/9 (11.1%)
Blood creatinine increased	0/8 (0%)		5/9 (55.6%)		0/9 (0%)
Blood lactate dehydrogenase increased	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Blood potassium decreased	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Blood uric acid increased	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Cardiac murmur	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Haemoglobin decreased	0/8 (0%)		1/9 (11.1%)		2/9 (22.2%)
Neutrophil count decreased	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Platelet count decreased	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Weight decreased	1/8 (12.5%)		2/9 (22.2%)		1/9 (11.1%)
Weight increased	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
White blood cell count decreased	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Metabolism and nutrition disorders
Decreased appetite	0/8 (0%)		2/9 (22.2%)		3/9 (33.3%)
Dehydration	0/8 (0%)		3/9 (33.3%)		0/9 (0%)
Fluid overload	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Gout	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Hyperglycaemia	3/8 (37.5%)		2/9 (22.2%)		2/9 (22.2%)
Hyperkalaemia	1/8 (12.5%)		2/9 (22.2%)		2/9 (22.2%)
Hypermagnesaemia	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Hypernatraemia	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Hyperphosphataemia	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Hypoalbuminaemia	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Hypocalcaemia	0/8 (0%)		3/9 (33.3%)		3/9 (33.3%)
Hypokalaemia	2/8 (25%)		3/9 (33.3%)		3/9 (33.3%)
Hypomagnesaemia	2/8 (25%)		1/9 (11.1%)		2/9 (22.2%)
Hyponatraemia	1/8 (12.5%)		2/9 (22.2%)		1/9 (11.1%)
Hypophosphataemia	2/8 (25%)		0/9 (0%)		1/9 (11.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/8 (12.5%)		2/9 (22.2%)		3/9 (33.3%)
Back pain	4/8 (50%)		3/9 (33.3%)		4/9 (44.4%)
Bone pain	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Fasciitis	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Gouty arthritis	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Intervertebral disc degeneration	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Joint swelling	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Limb discomfort	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Mobility decreased	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Muscle spasms	3/8 (37.5%)		1/9 (11.1%)		1/9 (11.1%)
Muscular weakness	1/8 (12.5%)		1/9 (11.1%)		0/9 (0%)
Musculoskeletal chest pain	0/8 (0%)		0/9 (0%)		2/9 (22.2%)
Musculoskeletal discomfort	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Musculoskeletal pain	2/8 (25%)		0/9 (0%)		0/9 (0%)
Myalgia	1/8 (12.5%)		1/9 (11.1%)		1/9 (11.1%)
Neck pain	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Osteoarthritis	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Osteonecrosis of jaw	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Pain in extremity	1/8 (12.5%)		2/9 (22.2%)		1/9 (11.1%)
Pain in jaw	1/8 (12.5%)		1/9 (11.1%)		0/9 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Nervous system disorders
Burning sensation	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Cerebrospinal fluid leakage	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Dizziness	0/8 (0%)		3/9 (33.3%)		2/9 (22.2%)
Dizziness postural	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Dysgeusia	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Dyskinesia	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Headache	1/8 (12.5%)		1/9 (11.1%)		1/9 (11.1%)
Hypoaesthesia	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Neuralgia	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Neuropathy peripheral	2/8 (25%)		1/9 (11.1%)		2/9 (22.2%)
Peripheral sensory neuropathy	0/8 (0%)		0/9 (0%)		2/9 (22.2%)
Sciatica	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Syncope	0/8 (0%)		4/9 (44.4%)		1/9 (11.1%)
Tremor	0/8 (0%)		2/9 (22.2%)		2/9 (22.2%)
Psychiatric disorders
Agitation	1/8 (12.5%)		1/9 (11.1%)		0/9 (0%)
Anxiety	1/8 (12.5%)		1/9 (11.1%)		1/9 (11.1%)
Confusional state	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Depression	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Insomnia	3/8 (37.5%)		0/9 (0%)		2/9 (22.2%)
Irritability	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Mood altered	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Mood swings	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Personality change	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Stress	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Renal and urinary disorders
Acute kidney injury	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Lower urinary tract symptoms	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Nephrolithiasis	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Nocturia	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Renal failure	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Urinary retention	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Reproductive system and breast disorders
Pelvic pain	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Vulvovaginal discomfort	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Cough	4/8 (50%)		2/9 (22.2%)		2/9 (22.2%)
Dysphonia	2/8 (25%)		1/9 (11.1%)		0/9 (0%)
Dyspnoea	3/8 (37.5%)		3/9 (33.3%)		3/9 (33.3%)
Dyspnoea exertional	1/8 (12.5%)		0/9 (0%)		1/9 (11.1%)
Epistaxis	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Hypoxia	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Nasal congestion	1/8 (12.5%)		2/9 (22.2%)		2/9 (22.2%)
Oropharyngeal pain	2/8 (25%)		2/9 (22.2%)		0/9 (0%)
Pleuritic pain	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Productive cough	1/8 (12.5%)		0/9 (0%)		1/9 (11.1%)
Pulmonary oedema	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Respiratory failure	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Rhinitis allergic	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Sinus congestion	2/8 (25%)		0/9 (0%)		0/9 (0%)
Tachypnoea	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Skin and subcutaneous tissue disorders
Alopecia	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Blood blister	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Decubitus ulcer	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Drug eruption	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Dry skin	1/8 (12.5%)		1/9 (11.1%)		0/9 (0%)
Ecchymosis	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Erythema	2/8 (25%)		1/9 (11.1%)		0/9 (0%)
Hyperhidrosis	4/8 (50%)		1/9 (11.1%)		0/9 (0%)
Miliaria	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Petechiae	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Pruritus	1/8 (12.5%)		0/9 (0%)		3/9 (33.3%)
Rash	2/8 (25%)		4/9 (44.4%)		1/9 (11.1%)
Rash erythematous	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Scab	1/8 (12.5%)		1/9 (11.1%)		0/9 (0%)
Skin discolouration	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Skin exfoliation	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Skin lesion	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Vascular disorders
Deep vein thrombosis	1/8 (12.5%)		1/9 (11.1%)		0/9 (0%)
Haematoma	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Hypertension	1/8 (12.5%)		1/9 (11.1%)		1/9 (11.1%)
Hypotension	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Superficial vein prominence	0/8 (0%)		0/9 (0%)		1/9 (11.1%)
Systolic hypertension	0/8 (0%)		1/9 (11.1%)		0/9 (0%)
Thrombosis	1/8 (12.5%)		0/9 (0%)		0/9 (0%)
Venous thrombosis limb	0/8 (0%)		0/9 (0%)		1/9 (11.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.