Trial Outcomes & Findings for Study of Elotuzumab in Combination With Lenalidomide and Dexamethasone in Subjects With Multiple Myeloma and Various Levels of Renal Function (NCT NCT01393964)

Last Updated: 2017-08-03

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

35 participants

Primary outcome timeframe

Day 1 of Cycle 1 to 28 days post dose

Results posted on

2017-08-03

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Elotuzumab + LD in Normal Renal Function(NRF) Participants 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 in Severe Renal Impairment(SRI) Participants 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 in End Stage Renal Disease(ESRD) Participants 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.
Overall Study STARTED	8	9	9
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	8	9	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Elotuzumab + LD in Normal Renal Function(NRF) Participants 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 in Severe Renal Impairment(SRI) Participants 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 in End Stage Renal Disease(ESRD) Participants 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.
Overall Study Disease Progression	4	3	5
Overall Study Study drug toxicity	1	0	0
Overall Study Withdrawal by Subject	0	0	1
Overall Study Adverse event unrelated to study drug	0	3	0
Overall Study Subject request stop study treatment	0	1	0
Overall Study Subject decided to move to transplant	1	0	0
Overall Study Subject switched to commercial supply	1	0	2
Overall Study Subject plateaued in terms of effect	1	0	0
Overall Study Investigator removed subject from study	0	1	0
Overall Study Subject converted to roll-over study	0	1	0
Overall Study Subject to receive non-protocol therapy	0	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Elotuzumab + LD in Normal Renal Function (NRF) Participants n=8 Participants 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).	Elotuzumab + LD in Severe Renal Impairment (SRI) Participants n=9 Participants 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.	Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants n=9 Participants 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 n=26 Participants Total of all reporting groups
Age, Continuous	57.8 years STANDARD_DEVIATION 8.05 • n=5 Participants	75.9 years STANDARD_DEVIATION 7.70 • n=7 Participants	55.6 years STANDARD_DEVIATION 11.70 • n=5 Participants	63.3 years STANDARD_DEVIATION 13.02 • n=4 Participants
Age, Customized < 65 years	7 participants n=5 Participants	1 participants n=7 Participants	8 participants n=5 Participants	16 participants n=4 Participants
Age, Customized >=65 and < 75 years	1 participants n=5 Participants	3 participants n=7 Participants	0 participants n=5 Participants	4 participants n=4 Participants
Age, Customized >= 75 years	0 participants n=5 Participants	5 participants n=7 Participants	1 participants n=5 Participants	6 participants n=4 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	10 Participants n=4 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	6 Participants n=7 Participants	5 Participants n=5 Participants	16 Participants n=4 Participants
Region of Enrollment United States	8 participants n=5 Participants	9 participants n=7 Participants	9 participants n=5 Participants	26 participants n=4 Participants

PRIMARY outcome

Timeframe: Day 1 of Cycle 1 to 28 days post dose

Population: 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.

Outcome measures

Outcome measures
Measure	Elotuzumab + LD in Normal Renal Function (NRF) Participants n=8 Participants 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 in Severe Renal Impairment (SRI) Participants n=7 Participants 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 in End Stage Renal Disease (ESRD) Participants n=8 Participants 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.
Geometric Mean Maximum Observed Serum Concentration (Cmax) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method	217 µg/mL Geometric Coefficient of Variation 24	226 µg/mL Geometric Coefficient of Variation 10	218 µg/mL Geometric Coefficient of Variation 21

PRIMARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Elotuzumab + LD in Normal Renal Function (NRF) Participants n=8 Participants 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 in Severe Renal Impairment (SRI) Participants n=7 Participants 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 in End Stage Renal Disease (ESRD) Participants n=8 Participants 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.
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 AUC (0-T)	39559 µg*h/mL Geometric Coefficient of Variation 28	50080 µg*h/mL Geometric Coefficient of Variation 20	45937 µg*h/mL Geometric Coefficient of Variation 31
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 AUC (INF)	46401 µg*h/mL Geometric Coefficient of Variation 39	60255 µg*h/mL Geometric Coefficient of Variation 31	51227 µg*h/mL Geometric Coefficient of Variation 39

SECONDARY outcome

Timeframe: From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)

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

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.

Outcome measures

Outcome measures
Measure	Elotuzumab + LD in Normal Renal Function (NRF) Participants n=8 Participants 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 in Severe Renal Impairment (SRI) Participants n=9 Participants 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 in End Stage Renal Disease (ESRD) Participants n=9 Participants 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.
Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Who Died Deaths	0 participants	0 participants	0 participants
Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Who Died AEs Leading to Discontinuation	1 participants	4 participants	1 participants
Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Who Died Any SAE	3 participants	5 participants	7 participants

SECONDARY outcome

Timeframe: From first dose (Day 1) to last dose plus 60 days, up to Primary Endpoint (June 2014), approximately 2 years

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

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.

Outcome measures

Outcome measures
Measure	Elotuzumab + LD in Normal Renal Function (NRF) Participants n=6 Participants 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 in Severe Renal Impairment (SRI) Participants n=4 Participants 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 in End Stage Renal Disease (ESRD) Participants n=6 Participants 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.
Number of Participants With Persistent Elotuzumab Anti-drug Antibodies (ADA) and Number of Participants ADA Positive at Cycle 2 Pre-dose. Baseline ADA Positive	1 participants	0 participants	0 participants
Number of Participants With Persistent Elotuzumab Anti-drug Antibodies (ADA) and Number of Participants ADA Positive at Cycle 2 Pre-dose. Positive at Cycle 2 pre-dose	2 participants	0 participants	1 participants
Number of Participants With Persistent Elotuzumab Anti-drug Antibodies (ADA) and Number of Participants ADA Positive at Cycle 2 Pre-dose. Persistent Positive	0 participants	0 participants	0 participants
Number of Participants With Persistent Elotuzumab Anti-drug Antibodies (ADA) and Number of Participants ADA Positive at Cycle 2 Pre-dose. Last Sample Positive	1 participants	0 participants	1 participants
Number of Participants With Persistent Elotuzumab Anti-drug Antibodies (ADA) and Number of Participants ADA Positive at Cycle 2 Pre-dose. Other Positive	1 participants	1 participants	0 participants
Number of Participants With Persistent Elotuzumab Anti-drug Antibodies (ADA) and Number of Participants ADA Positive at Cycle 2 Pre-dose. On-Study ADA Negative	4 participants	3 participants	5 participants
Number of Participants With Persistent Elotuzumab Anti-drug Antibodies (ADA) and Number of Participants ADA Positive at Cycle 2 Pre-dose. On-Study ADA Positive	2 participants	1 participants	1 participants

SECONDARY outcome

Timeframe: From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)

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

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.

Outcome measures

Outcome measures
Measure	Elotuzumab + LD in Normal Renal Function (NRF) Participants n=8 Participants 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 in Severe Renal Impairment (SRI) Participants n=9 Participants 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 in End Stage Renal Disease (ESRD) Participants n=9 Participants 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.
Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests Leukocytes Any Grade	8 participants	8 participants	6 participants
Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests Lymphocytes (Abs) Any Grade	8 participants	9 participants	9 participants
Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests Lymphocytes (Abs) Grade 3-4	6 participants	9 participants	5 participants
Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests Neutrophil Count (Abs) Grade 3-4	3 participants	1 participants	2 participants
Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests Hemoglobin Any Grade	8 participants	9 participants	9 participants
Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests Hemoglobin Grade 3-4	0 participants	2 participants	6 participants
Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests Platelet Count Any Grade	7 participants	8 participants	8 participants
Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests Platelet Count Grade 3-4	0 participants	2 participants	2 participants
Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests Leukocytes Grade 3-4	3 participants	1 participants	2 participants
Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests Neutrophil Count (Abs) Any Grade	6 participants	5 participants	6 participants

SECONDARY outcome

Timeframe: From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)

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

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.

Outcome measures

Outcome measures
Measure	Elotuzumab + LD in Normal Renal Function (NRF) Participants n=8 Participants 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 in Severe Renal Impairment (SRI) Participants n=9 Participants 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 in End Stage Renal Disease (ESRD) Participants n=9 Participants 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.
Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests AST Any Grade	3 participants	2 participants	5 participants
Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests ALT Any Grade	2 participants	5 participants	5 participants
Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests Bilirubin Any Grade	1 participants	1 participants	2 participants
Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests Bilirubin Grade 3-4	0 participants	0 participants	0 participants
Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests Creatinine Any Grade	0 participants	9 participants	9 participants
Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests Albumin Any Grade	2 participants	7 participants	7 participants
Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests Albumin Grade 3-4	0 participants	0 participants	0 participants
Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests ALP Any Grade	0 participants	3 participants	7 participants
Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests ALP Grade 3-4	0 participants	0 participants	0 participants
Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests AST Grade 3-4	0 participants	0 participants	0 participants
Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests ALT Grade 3-4	0 participants	0 participants	0 participants
Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests Creatinine Grade 3-4	0 participants	2 participants	9 participants

SECONDARY outcome

Timeframe: From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)

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

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.

Outcome measures

Outcome measures
Measure	Elotuzumab + LD in Normal Renal Function (NRF) Participants n=8 Participants 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 in Severe Renal Impairment (SRI) Participants n=9 Participants 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 in End Stage Renal Disease (ESRD) Participants n=9 Participants 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.
Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests Potassium High Any Grade	2 participants	2 participants	4 participants
Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests Potassium High Grade 3-4	0 participants	0 participants	3 participants
Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests Potassium Low Any Grade	2 participants	5 participants	6 participants
Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests Potassium Low Grade 3-4	0 participants	2 participants	1 participants
Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests Bicarbonate Grade 3-4	0 participants	0 participants	0 participants
Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests Calcium High Any Grade	1 participants	0 participants	3 participants
Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests Calcium High Grade 3-4	0 participants	0 participants	1 participants
Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests Glucose High Any Grade	7 participants	9 participants	7 participants
Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests Glucose High Grade 3-4	3 participants	4 participants	3 participants
Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests Glucose Low Any Grade	1 participants	0 participants	1 participants
Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests Glucose Low Grade 3-4	0 participants	0 participants	0 participants
Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests Sodium High Any Grade	2 participants	3 participants	2 participants
Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests Sodium High Grade 3-4	0 participants	0 participants	0 participants
Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests Sodium Low Any Grade	2 participants	6 participants	5 participants
Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests Sodium Low Grade 3-4	1 participants	1 participants	0 participants
Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests Bicarbonate Any Grade	5 participants	8 participants	6 participants
Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests Calcium Low Any Grade	4 participants	6 participants	8 participants
Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests Calcium Low Grade 3-4	0 participants	1 participants	2 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1 of Cycle 1 to 28 days post dose

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Elotuzumab + LD in Normal Renal Function (NRF) Participants n=8 Participants 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 in Severe Renal Impairment (SRI) Participants n=7 Participants 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 in End Stage Renal Disease (ESRD) Participants n=8 Participants 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.
Mean Terminal-phase Elimination Half-life (T-Half) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method	204 h Standard Deviation 134.11	237 h Standard Deviation 107.88	218 h Standard Deviation 98.87

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Elotuzumab + LD in Normal Renal Function (NRF) Participants n=8 Participants 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 in Severe Renal Impairment (SRI) Participants n=7 Participants 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 in End Stage Renal Disease (ESRD) Participants n=8 Participants 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.
Median Time to Maximal Concentration (Tmax) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method	3.23 h Interval 2.9 to 4.9	3.87 h Interval 2.8 to 6.8	3.33 h Interval 2.82 to 25.92

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Elotuzumab + LD in Normal Renal Function (NRF) Participants n=8 Participants 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 in Severe Renal Impairment (SRI) Participants n=7 Participants 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 in End Stage Renal Disease (ESRD) Participants n=8 Participants 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.
Geometric Mean Total Body Clearance (CLT) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method	0.215 mL/h/kg Geometric Coefficient of Variation 46	0.166 mL/h/kg Geometric Coefficient of Variation 28	0.195 mL/h/kg Geometric Coefficient of Variation 54

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Elotuzumab + LD in Normal Renal Function (NRF) Participants n=8 Participants 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 in Severe Renal Impairment (SRI) Participants n=7 Participants 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 in End Stage Renal Disease (ESRD) Participants n=8 Participants 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.
Geometric Mean Apparent Volume of Distribution (Vz) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method	59.4 mL/kg Geometric Coefficient of Variation 30	54.6 mL/kg Geometric Coefficient of Variation 20	61.2 mL/kg Geometric Coefficient of Variation 43

Adverse Events

Elotuzumab + LD in Normal Renal Function (NRF) Participants

Serious events: 3 serious events

Other events: 8 other events

Deaths: 0 deaths

Elotuzumab + LD in Severe Renal Impairment (SRI) Participants

Serious events: 5 serious events

Other events: 9 other events

Deaths: 0 deaths

Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants

Serious events: 7 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Elotuzumab + LD in Normal Renal Function (NRF) Participants n=8 participants at risk 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 in Severe Renal Impairment (SRI) Participants n=9 participants at risk 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 in End Stage Renal Disease (ESRD) Participants n=9 participants at risk 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.
Blood and lymphatic system disorders Anaemia macrocytic	0.00% 0/8 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	0.00% 0/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	11.1% 1/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/8 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	0.00% 0/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	22.2% 2/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
Cardiac disorders Atrial fibrillation	0.00% 0/8 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	11.1% 1/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	11.1% 1/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
Cardiac disorders Bradycardia	0.00% 0/8 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	0.00% 0/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	11.1% 1/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
Cardiac disorders Tachycardia	0.00% 0/8 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	0.00% 0/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	11.1% 1/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
Endocrine disorders Hypothyroidism	0.00% 0/8 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	0.00% 0/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	11.1% 1/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
Gastrointestinal disorders Abdominal pain	0.00% 0/8 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	11.1% 1/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	0.00% 0/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
Gastrointestinal disorders Diarrhoea	0.00% 0/8 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	0.00% 0/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	11.1% 1/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
General disorders Chest discomfort	0.00% 0/8 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	0.00% 0/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	11.1% 1/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
General disorders Chest pain	0.00% 0/8 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	0.00% 0/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	11.1% 1/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
General disorders Pyrexia	0.00% 0/8 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	0.00% 0/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	11.1% 1/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
Hepatobiliary disorders Cholecystitis	0.00% 0/8 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	11.1% 1/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	0.00% 0/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
Infections and infestations Bronchitis	0.00% 0/8 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	11.1% 1/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	11.1% 1/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
Infections and infestations Clostridium difficile infection	0.00% 0/8 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	11.1% 1/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	0.00% 0/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
Infections and infestations Gastroenteritis salmonella	0.00% 0/8 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	0.00% 0/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	11.1% 1/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
Infections and infestations Influenza	0.00% 0/8 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	0.00% 0/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	11.1% 1/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
Infections and infestations Meningitis bacterial	0.00% 0/8 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	0.00% 0/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	11.1% 1/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
Infections and infestations Pneumonia	12.5% 1/8 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	0.00% 0/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	22.2% 2/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
Infections and infestations Pneumonia respiratory syncytial viral	0.00% 0/8 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	11.1% 1/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	0.00% 0/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
Infections and infestations Sepsis	12.5% 1/8 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	0.00% 0/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	0.00% 0/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
Infections and infestations Soft tissue infection	0.00% 0/8 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	11.1% 1/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	0.00% 0/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
Infections and infestations Staphylococcal bacteraemia	0.00% 0/8 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	0.00% 0/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	11.1% 1/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
Infections and infestations Upper respiratory tract infection	0.00% 0/8 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	11.1% 1/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	11.1% 1/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
Investigations Blood creatinine increased	0.00% 0/8 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	0.00% 0/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	11.1% 1/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
Investigations Influenza a virus test positive	0.00% 0/8 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	0.00% 0/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	11.1% 1/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
Metabolism and nutrition disorders Gout	0.00% 0/8 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	11.1% 1/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	0.00% 0/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/8 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	0.00% 0/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	11.1% 1/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/8 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	11.1% 1/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	0.00% 0/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/8 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	0.00% 0/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	11.1% 1/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
Metabolism and nutrition disorders Hyperphosphataemia	0.00% 0/8 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	0.00% 0/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	11.1% 1/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/8 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	0.00% 0/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	11.1% 1/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/8 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	0.00% 0/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	11.1% 1/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	12.5% 1/8 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	0.00% 0/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	0.00% 0/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
Vascular disorders Deep vein thrombosis	0.00% 0/8 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	0.00% 0/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	11.1% 1/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
Vascular disorders Hypertensive crisis	0.00% 0/8 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	11.1% 1/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	0.00% 0/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
Vascular disorders Hypotension	0.00% 0/8 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	11.1% 1/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)	11.1% 1/9 • From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)