ELOQUENT - 1: Phase III Study of Lenalidomide and Dexamethasone With or Without Elotuzumab to Treat Newly Diagnosed, Previously Untreated Multiple Myeloma

Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Completed
CT.gov ID
NCT01335399
Collaborator
AbbVie (Industry)
748
232
2
121
3.2
0

Study Details

Study Description

Brief Summary

The purpose of the study is to determine whether the addition of Elotuzumab to Lenalidomide/low-dose Dexamethasone will increase the progression free survival (PFS)

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
748 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 3, Randomized, Open Label Trial of Lenalidomide/Dexamethasone With or Without Elotuzumab in Subjects With Previously Untreated Multiple Myeloma
Actual Study Start Date :
Aug 4, 2011
Actual Primary Completion Date :
Oct 1, 2019
Actual Study Completion Date :
Sep 3, 2021

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Lenalidomide + Dexamethasone

Drug: Lenalidomide
Capsules, Oral, 25 mg, once daily, on Days 1-21, Repeat every 28 days until subject meets criteria for discontinuation of study drug
Other Names:
  • Revlimid®
  • Drug: Dexamethasone
    Tablets, Oral, 40 mg, weekly, on Days 1, 8, 15, 22, Repeat every 28 days until subject meets criteria for discontinuation of study drug
    Other Names:
  • Decadron®
  • Dexamethasone Intensol®
  • Dexpak®
  • Taperpak®
  • Experimental: Lenalidomide + Dexamethasone + Elotuzumab

    Drug: Lenalidomide
    Capsules, Oral, 25 mg, once daily, on 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, once daily, on Days 1, 8, 15, 22 (cycles 1&2) ; Days 1 &15 (cycles 3-18); Day 1 (cycle 19 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, once daily, on Days 8 & 22 (cycles 3-18); Days 8, 15, 22 (cycle 19 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 (IV), 8 mg, Once daily, on Days 1, 8, 15, 22 (cycles 1&2) ; Days 1 &15 (cycles 3-18); Day 1 (cycle 19 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 (IV), 10 mg/kg, weekly, on Days 1, 8, 15, 22 (cycles 1&2); Days 1 and 15 (cycles 3-18), Repeat every 28 days until subject meets criteria for discontinuation of study drug

    Biological: Elotuzumab (BMS-901608; HuLuc63)
    Solution, Intravenous (IV), 20 mg/kg, Day 1 (cycle 19 and beyond), Repeat every 28 days until subject meets criteria for discontinuation of study drug

    Outcome Measures

    Primary Outcome Measures

    1. Progression-Free Survival (PFS) [From randomization to date of first documented tumor progression or death due to any cause (up to 8 years)]

      PFS is defined as the time from randomization to the date of the first documented tumor progression (as determined by the Independent Review Committee (IRC)) or death due to any cause. The IRC conducted a blinded, independent review of the tumor assessments based on the European Group for Blood and Bone Marrow Transplant (EBMT) criteria. Censoring rules applied: Participants receiving subsequent systemic anti-myeloma therapy prior to documented progression were censored at the date of the last adequate tumor assessment prior to new therapy. Participants who had an event (progression or death) > 10 weeks after their last tumor assessment were censored at their last adequate tumor assessment prior to the event. Participants without progression or death (and not receiving subsequent therapy prior to progression) were censored at their last adequate tumor assessment. Participants without any post-baseline tumor assessments were censored on the date of randomization

    Secondary Outcome Measures

    1. Objective Response Rate (ORR) [From randomization to primary completion date (approximately 8 years)]

      ORR is defined as the percentage of participants with objective response among all randomized subjects. Participants with an objective response are those participants experiencing a partial response (PR) or better, based on Indipendent Review Committee (IRC) assessment, as per EBMT criteria.

    2. Overall Survival (OS) [From randomization to the date of death (up to 8 years)]

      Survival is defined as the time from randomization to the date of death. A participant who did not die had his or her survival duration censored at the date of last contact ('last known date alive").

    3. Mean Change From Baseline of Pain Severity Score and Pain Interference Score [From Baseline to End of Treatment (approximately 8 years)]

      Pain severity (sensory dimension) and pain interference (reactive dimension, assessing the degree to which pain interferes with function) are measured using the Brief Pain Inventory- Short Form (BPI-SF). BPI-SF numeric rating scale goes from 0 (No pain) to 10 (Pain as bad as you can imagine).

    4. Progression Free Survival (PFS) Rate at Specific Time-points [From randomization to the specified time-point (up to 5 years)]

      PFS rate is defined as the proportion of participants experiencing PFS at the defined time-points.

    Eligibility Criteria

    Criteria

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

    For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.

    Inclusion Criteria:
    • Subjects who are newly diagnosed with symptomatic Multiple Myeloma (MM) and who:

    • have not received any prior systemic anti-myeloma therapy AND

    • have measurable disease AND

    • are not candidates for high-dose therapy plus stem-cell transplantation (SCT) because of age (≥ 65 years) or coexisting conditions. Refusal to undergo high dose therapy with SCT is NOT sufficient for entry onto CA204006 for a subject < 65 years old. There must be a comorbidity that prevents SCT for a subject < 65 years old

    Exclusion Criteria:
    • Subjects with non-secretory or oligo-secretory or free light-chain only myeloma

    • Smoldering MM, defined as asymptomatic MM with absence of lytic bone lesions

    • Monoclonal Gammopathy of Undetermined Significance (MGUS)

    • Active plasma cell leukemia

    • Known Human Immunodeficiency Virus (HIV) infection or active hepatitis A, B, or C

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Alabama Oncology Birmingham Alabama United States 35243
    2 University Of South Alabama / Mitchell Cancer Institute Mobile Alabama United States 36604
    3 Southern Cancer Center, Inc. Mobile Alabama United States 36608
    4 Ironwood Cancer And Research Centers, Pc Chandler Arizona United States 85224
    5 Acrc/Arizona Clinical Research Center, Inc. Tucson Arizona United States 85715
    6 Comprehensive Blood And Cancer Center Bakersfield California United States 93309
    7 Alta Bates Summit Comprehensive Cancer Center Berkeley California United States 94704
    8 Compassionate Cancer Care Medical Group, Inc. Corona California United States 92879
    9 Compassionate Cancer Res Grp Corona California United States 92879
    10 Marin Cancer Care, Inc Greenbrae California United States 94904
    11 Pacific Shores Medical Group Long Beach California United States 90813
    12 Ucla-Division Of Hematology/Oncology Los Angeles California United States 90095
    13 Medical Oncology Care Associates Orange California United States 92868
    14 Sharp Clinical Oncology Research San Diego California United States 92123
    15 Yale University School Of Medicine New Haven Connecticut United States 06520
    16 Washington Cancer Inst at MedStar Washington Hospital Ctr Washington District of Columbia United States 20010
    17 Lynn Cancer Institute Center For Hematology-Oncology Boca Raton Florida United States 33486
    18 Local Institution Brooksville Florida United States 34613
    19 Florida Cancer Specialists S. Fort Myers Florida United States 33916
    20 Memorial Cancer Institute Hollywood Florida United States 33021
    21 Cancer Specialists, LLC Jacksonville Florida United States 32256
    22 Local Institution New Port Richey Florida United States 34652
    23 Florida Cancer Specialists Saint Petersburg Florida United States 33705
    24 Palm Beach Cancer Institute West Palm Beach Florida United States 33401
    25 Winship Cancer Institute. Atlanta Georgia United States 30322
    26 Kaiser Permanente Hawaii Honolulu Hawaii United States 96819
    27 The University Of Chicago Chicago Illinois United States 19123
    28 Rush University Medical Center Chicago Illinois United States 60612
    29 Loyola University Chicago Maywood Illinois United States 60153
    30 Illinois Cancercare, PC Peoria Illinois United States 61615
    31 Orchard Healthcare Research Inc. Skokie Illinois United States 60077
    32 Carle Cancer Center Urbana Illinois United States 61801
    33 Premier Healthcare, Llc Bloomington Indiana United States 47403
    34 Franciscan St. Francis Health Indianapolis Indiana United States 46237
    35 Investigative Clinical Research Of Indiana, Llc Indianapolis Indiana United States 46260
    36 Local Institution Mishawaka Indiana United States 46545
    37 University Of Iowa Hospitals And Clinics Iowa City Iowa United States 52242
    38 Baptist Health Lexington Lexington Kentucky United States 40503
    39 Norton Cancer Institute Louisville Kentucky United States 40207
    40 Cancer Center Of Acadiana At Lafayette General Lafayette Louisiana United States 70503
    41 Crescent City Research Consortium, LLC Marrero Louisiana United States 70072
    42 Ochsner Clinic Foundation New Orleans Louisiana United States 70121
    43 Willis Knighton Cancer Center Shreveport Louisiana United States 71103
    44 Greater Baltimore Medical Center Baltimore Maryland United States 21204
    45 Harry & Jeanette Weinberg Cancer Institute Baltimore Maryland United States 21237
    46 Dana Farber Cancer Institute. Boston Massachusetts United States 02215
    47 Dana-Farber Cancer Institute Boston Massachusetts United States 02215
    48 Henry Ford Health System Detroit Michigan United States 48202
    49 Columbia Comprehensive Cancer Care Clinic Jefferson City Missouri United States 65101
    50 Washington University School Of Medicine Saint Louis Missouri United States 63110
    51 Mercy Medical Research Institute Springfield Missouri United States 65804
    52 University Of Nebraska Medical Center Omaha Nebraska United States 68198-7680
    53 Winthrop University Hospital Mineola New York United States 11501
    54 Local Institution New York New York United States 10019
    55 Stony Brook University Medical Center Stony Brook New York United States 11794-8183
    56 Southeastern Medical Oncology Center Goldsboro North Carolina United States 27534
    57 Novant Health Oncology Specialists Winston-Salem North Carolina United States 27103
    58 Cleveland Clinic Cleveland Ohio United States 44195
    59 Benson, Md, Don Columbus Ohio United States 43210
    60 Mid Ohio Onc/Hema, Inc., Dba Columbus Ohio United States 43219
    61 Signal Point Clinical Research Center, Llc Middletown Ohio United States 45042
    62 Oklahoma Cancer Specialists and Research Institute, LLC-Clinical Research Tulsa Oklahoma United States 74146
    63 Alliance Cancer Specialists Langhorne Pennsylvania United States 19047
    64 Western Pennsylvania Hospital Pittsburgh Pennsylvania United States 15224
    65 Va Pittsburgh Healthcare System Pittsburgh Pennsylvania United States 15240
    66 Donald Guthrie Foundation Sayre Pennsylvania United States 18840
    67 Charleston Hematology Oncology Associates, Pa Charleston South Carolina United States 29414
    68 Local Institution - 7615 Charleston South Carolina United States 29425
    69 GHS Cancer Institute Greenville South Carolina United States 29615
    70 Avera Cancer Institute Sioux Falls South Dakota United States 57105
    71 Tennessee Cancer Specialists Knoxville Tennessee United States 37909
    72 Baptist Cancer Center Memphis Tennessee United States 38120
    73 Tennessee Oncology, Pc Nashville Tennessee United States 37203
    74 Vanderbilt University Medical Center Nashville Tennessee United States 37232-5505
    75 Cancer Specialists Of South Texas, Pa Corpus Christi Texas United States 78412
    76 Baylor Charles A. Sammons Cancer Center Dallas Texas United States 75246
    77 Baylor College Of Medicine Houston Texas United States 77030
    78 Michael E Debakey VA Medical Center Houston Texas United States 77030
    79 Northwest Cancer Center Houston Texas United States 77090
    80 Community Cancer Trials of Utah Ogden Utah United States 84405
    81 Hematology-Oncology Associates Of Fredricksburg, Inc Fredericksburg Virginia United States 22408
    82 Va Puget Sound Health Care System Seattle Washington United States 98108
    83 Fred Hutchinson Cancer Research Ctr Seattle Washington United States 98109
    84 Edwards Comprehensive Cancer Center Huntington West Virginia United States 25701
    85 Gundersen Clinic, Ltd La Crosse Wisconsin United States 54601
    86 Dean Clinic-Hematology And Oncology Madison Wisconsin United States 53717
    87 University Of Wisconsin Hospital And Clinics Madison Wisconsin United States 53792
    88 Local Institution Garran Australian Capital Territory Australia 2605
    89 Local Institution Waratah New South Wales Australia 2298
    90 Local Institution Westmead New South Wales Australia 2145
    91 Local Institution Herston Queensland Australia 4029
    92 Local Institution Milton Queensland Australia 4064
    93 Local Institution Adelaide South Australia Australia 5000
    94 Local Institution - 3606 Woodville South South Australia Australia 5001
    95 Local Institution Fitzroy Victoria Australia 3065
    96 Local Institution Frankston Victoria Australia 3199
    97 Local Institution Heidelberg Melbourne Victoria Australia 3084
    98 Local Institution Wodonga Victoria Australia 3690
    99 Local Institution Murdoch Australia 6150
    100 Local Institution Nedlands Australia 6009
    101 Local Institution Fadingerstraße 1 Austria 4020
    102 Local Institution Innsbruck Austria 6020
    103 Local Institution Rankweil Austria 6830
    104 Local Institution Wels Austria 4600
    105 Local Institution Brussels Belgium 1020
    106 Local Institution Brussels Belgium 1090
    107 Local Institution Brussles Belgium 1200
    108 Local Institution Charleroi Belgium 6000
    109 Local Institution Haine St Paul Belgium 7100
    110 Local Institution Leuven Belgium 3000
    111 Local Institution Liege Belgium 4000
    112 Local Institution Roeselare Belgium 8800
    113 Local Institution Yvoir Belgium 5530
    114 Local Institution Calgary Alberta Canada T2N 4N2
    115 Local Institution Edmonton Alberta Canada T6G 1Z2
    116 Local Institution Winnipeg Manitoba Canada R3E 0V9
    117 Local Institution Saint John New Brunswick Canada E2L 4L2
    118 Local Institution Halifax Nova Scotia Canada B3H 2Y9
    119 Local Institution London Ontario Canada N6A 5W9
    120 Local Institution Toronto Ontario Canada M5G 2M9
    121 Local Institution Greenfield Park Quebec Canada J4V 2H1
    122 Local Institution Montreal Quebec Canada H1T 2M4
    123 Local Institution Montreal Quebec Canada H3A 1A1
    124 Local Institution Hradec Kralove Czechia 500 05
    125 Local Institution Praha 10 Czechia 100 34
    126 Local Institution Praha 2 Czechia 128 08
    127 Local Institution Aschaffenburg Germany 63739
    128 Local Institution - 4550 Berlin Germany 12200
    129 Local Institution Chemnitz Germany 09113
    130 Local Institution Dresden Germany 01307
    131 Local Institution Hamm Germany 59063
    132 Local Institution Heidelberg Germany 69120
    133 Local Institution - 4560 Jena Germany 07747
    134 Local Institution - 4563 Koln Germany 50937
    135 Local Institution Mainz Germany 55101
    136 Local Institution Munchen Germany 81377
    137 Local Institution Munster Germany 48149
    138 Local Institution Offenbach Germany 63069
    139 Local Institution Stuttgart Germany 70376
    140 Local Institution Tuebingen Germany 72076
    141 Local Institution Ulm Germany 89081
    142 Local Institution Athens Greece 11527
    143 Local Institution Athens Greece 11528
    144 Local Institution Ioannina Greece 45500
    145 Local Institution Larissa Greece 41110
    146 Local Institution Patras Greece 26504
    147 Local Institution Budapest Hungary 1097
    148 Local Institution Budapest Hungary 1122
    149 Local Institution - 4750 Debrecen Hungary 4012
    150 Local Institution Gyor Hungary 9024
    151 Local Institution - 4752 Szeged Hungary 6720
    152 Local Institution Dublin Ireland 7
    153 Local Institution Dublin Ireland 8
    154 Local Institution Galway Ireland
    155 Local Institution Afula Israel 1834111
    156 Local Institution Ashkelon Israel 7830604
    157 Local Institution - 4960 Haifa Israel 3109601
    158 Local Institution Jerusalem Israel 91031
    159 Local Institution Jerusalem Israel 91120
    160 Local Institution Kfar Saba Israel 4428164
    161 Local Institution Nahariya Israel 2210001
    162 Local Institution Petah Tikva Israel 4941492
    163 Local Institution Tel Aviv Israel 64239
    164 Local Institution Zerifin Israel 70300
    165 Local Institution Ancona Italy 60126
    166 Local Institution Bari Italy 70124
    167 Local Institution Bergamo Italy 24127
    168 Local Institution Bologna Italy 40138
    169 Local Institution Firenze Italy 50134
    170 Local Institution Genova Italy 16132
    171 Local Institution Meldola Italy 47014
    172 Local Institution Milano Italy 20122
    173 Local Institution Milan Italy 20132
    174 Local Institution Monza Italy 20052
    175 Local Institution Napoli Italy 80131
    176 Local Institution Palermo Italy 90146
    177 Local Institution Ravenna Italy 48100
    178 Local Institution Reggio Nell Emilia (RE) Italy 42100
    179 Local Institution Rimini Italy 47923
    180 Local Institution Roma Italy 00144
    181 Local Institution Roma Italy 00168
    182 Local Institution Rome Italy 00161
    183 Local Institution Terni Italy 05100
    184 Local Institution Torino Italy 10126
    185 Local Institution Bialystok Poland 15-276
    186 Local Institution Chorzow Poland 41-500
    187 Local Institution Gdansk Poland 80-952
    188 Local Institution Krakow Poland 31-531
    189 Local Institution Lodz Poland 93-510
    190 Local Institution Lublin Poland 20-081
    191 Local Institution Poznan Poland 60-569
    192 Local Institution Szczecin Poland 70-111
    193 Local Institution Warszawa Poland 02-106
    194 Local Institution Warszawa Poland 02-507
    195 Local Institution Warszawa Poland 02-776
    196 Local Institution Wroclaw Poland 50-367
    197 Local Institution Ponce Puerto Rico 00716
    198 Local Institution San Juan Puerto Rico 00918
    199 Local Institution Brasov Romania 500152
    200 Local Institution Bucaresti Romania 030171
    201 Local Institution Bucuresti Romania 020125
    202 Local Institution Bucuresti Romania 050098
    203 Local Institution Bucuresti Romania 22328
    204 Local Institution Lasi Romania 700483
    205 Local Institution Samara Russian Federation 443095
    206 Local Institution St. Petersburg Russian Federation 197022
    207 Local Institution - 5552 Badalona-barcelona Spain 08916
    208 Local Institution Barcelona Spain 08036
    209 Local Institution Barcelona Spain 08041
    210 Local Institution La Laguna- Tenerife Spain 38320
    211 Local Institution Madrid Spain 28006
    212 Local Institution Madrid Spain 28007
    213 Local Institution Madrid Spain 28034
    214 Local Institution Madrid Spain 28041
    215 Local Institution Pamplona Spain 31008
    216 Local Institution Salamanca Spain 37007
    217 Local Institution San Sebastian Spain 20014
    218 Local Institution Toledo Spain 45004
    219 Local Institution Bern Switzerland 3010
    220 Local Institution St Gallen Switzerland 9007
    221 Local Institution Zurich Switzerland 8028
    222 Local Institution Zurich Switzerland 8091
    223 Local Institution - 5853 Izmir Bornova Turkey 35100
    224 Local Institution - 5851 Ankara Dikimevi Turkey 06620
    225 Local Institution Izmir Inciralti Turkey 35340
    226 Local Institution Gaziantep Turkey 27310
    227 Local Institution Belfast Antrim United Kingdom BT9 7AB
    228 Local Institution London Greater London United Kingdom SE5 9RS
    229 Local Institution London United Kingdom EC1A 7BE
    230 Local Institution London United Kingdom HA1 3UJ
    231 Local Institution London United Kingdom NW1 2PG
    232 Local Institution London United Kingdom NW3 2QG

    Sponsors and Collaborators

    • Bristol-Myers Squibb
    • AbbVie

    Investigators

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

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Bristol-Myers Squibb
    ClinicalTrials.gov Identifier:
    NCT01335399
    Other Study ID Numbers:
    • CA204-006
    • 2010-022445-20
    First Posted:
    Apr 14, 2011
    Last Update Posted:
    Jul 20, 2022
    Last Verified:
    Jul 1, 2022

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail E-Ld cohort: 374 participants were randomized. 371 participants entered the treatment period. Ld cohort: 374 participants were randomized. 371 participants entered the treatment period.
    Arm/Group Title E-Ld Cohort Ld Cohort
    Arm/Group Description Participants receiving a combination of Elotuzumab (E) Lenalidomide (L) Dexamethasone (d) in a 28 day cycle Participants receiving a combination of Lenalidomide (L) Dexamethasone (d) in a 28 day cycle
    Period Title: Pre-treatment Period
    STARTED 374 374
    COMPLETED 371 371
    NOT COMPLETED 3 3
    Period Title: Pre-treatment Period
    STARTED 371 371
    COMPLETED 38 32
    NOT COMPLETED 333 339

    Baseline Characteristics

    Arm/Group Title E-Ld Cohort Ld Cohort Total
    Arm/Group Description Participants receiving a combination of Elotuzumab (E) Lenalidomide (L) Dexamethasone (d) in a 28 day cycle Participants receiving a combination of Lenalidomide (L) Dexamethasone (d) in a 28 day cycle Total of all reporting groups
    Overall Participants 374 374 748
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    72.9
    (6.58)
    73.1
    (6.70)
    73.0
    (6.63)
    Sex: Female, Male (Count of Participants)
    Female
    163
    43.6%
    173
    46.3%
    336
    44.9%
    Male
    211
    56.4%
    201
    53.7%
    412
    55.1%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    9
    2.4%
    8
    2.1%
    17
    2.3%
    Not Hispanic or Latino
    70
    18.7%
    87
    23.3%
    157
    21%
    Unknown or Not Reported
    295
    78.9%
    279
    74.6%
    574
    76.7%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    1
    0.3%
    4
    1.1%
    5
    0.7%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    1
    0.3%
    1
    0.1%
    Black or African American
    13
    3.5%
    16
    4.3%
    29
    3.9%
    White
    360
    96.3%
    351
    93.9%
    711
    95.1%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    2
    0.5%
    2
    0.3%

    Outcome Measures

    1. Primary Outcome
    Title Progression-Free Survival (PFS)
    Description PFS is defined as the time from randomization to the date of the first documented tumor progression (as determined by the Independent Review Committee (IRC)) or death due to any cause. The IRC conducted a blinded, independent review of the tumor assessments based on the European Group for Blood and Bone Marrow Transplant (EBMT) criteria. Censoring rules applied: Participants receiving subsequent systemic anti-myeloma therapy prior to documented progression were censored at the date of the last adequate tumor assessment prior to new therapy. Participants who had an event (progression or death) > 10 weeks after their last tumor assessment were censored at their last adequate tumor assessment prior to the event. Participants without progression or death (and not receiving subsequent therapy prior to progression) were censored at their last adequate tumor assessment. Participants without any post-baseline tumor assessments were censored on the date of randomization
    Time Frame From randomization to date of first documented tumor progression or death due to any cause (up to 8 years)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants
    Arm/Group Title E-Ld Cohort Ld Cohort
    Arm/Group Description Participants receiving a combination of Elotuzumab (E) Lenalidomide (L) Dexamethasone (d) in a 28 day cycle Participants receiving a combination of Lenalidomide (L) Dexamethasone (d) in a 28 day cycle
    Measure Participants 374 374
    Median (95% Confidence Interval) [Months]
    31.38
    29.47
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection E-Ld Cohort, Ld Cohort
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4358
    Comments
    Method Stratified Log Rank
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection E-Ld Cohort, Ld Cohort
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.93
    Confidence Interval (2-Sided) 95.71%
    0.77 to 1.12
    Parameter Dispersion Type:
    Value:
    Estimation Comments E-Ld/Ld. Calculated using Cox proportional hazards modeling
    2. Secondary Outcome
    Title Objective Response Rate (ORR)
    Description ORR is defined as the percentage of participants with objective response among all randomized subjects. Participants with an objective response are those participants experiencing a partial response (PR) or better, based on Indipendent Review Committee (IRC) assessment, as per EBMT criteria.
    Time Frame From randomization to primary completion date (approximately 8 years)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants
    Arm/Group Title E-Ld Cohort Ld Cohort
    Arm/Group Description Participants receiving a combination of Elotuzumab (E) Lenalidomide (L) Dexamethasone (d) in a 28 day cycle Participants receiving a combination of Lenalidomide (L) Dexamethasone (d) in a 28 day cycle
    Measure Participants 374 374
    Number (95% Confidence Interval) [Percent of Participants]
    82.9
    22.2%
    79.4
    21.2%
    3. Secondary Outcome
    Title Overall Survival (OS)
    Description Survival is defined as the time from randomization to the date of death. A participant who did not die had his or her survival duration censored at the date of last contact ('last known date alive").
    Time Frame From randomization to the date of death (up to 8 years)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants
    Arm/Group Title E-Ld Cohort Ld Cohort
    Arm/Group Description Participants receiving a combination of Elotuzumab (E) Lenalidomide (L) Dexamethasone (d) in a 28 day cycle Participants receiving a combination of Lenalidomide (L) Dexamethasone (d) in a 28 day cycle
    Measure Participants 374 374
    Median (95% Confidence Interval) [Months]
    60.42
    57.56
    4. Secondary Outcome
    Title Mean Change From Baseline of Pain Severity Score and Pain Interference Score
    Description Pain severity (sensory dimension) and pain interference (reactive dimension, assessing the degree to which pain interferes with function) are measured using the Brief Pain Inventory- Short Form (BPI-SF). BPI-SF numeric rating scale goes from 0 (No pain) to 10 (Pain as bad as you can imagine).
    Time Frame From Baseline to End of Treatment (approximately 8 years)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants
    Arm/Group Title E-Ld Cohort Ld Cohort
    Arm/Group Description Participants receiving a combination of Elotuzumab (E) Lenalidomide (L) Dexamethasone (d) in a 28 day cycle Participants receiving a combination of Lenalidomide (L) Dexamethasone (d) in a 28 day cycle
    Measure Participants 374 374
    Pain Severity
    0.02
    (2.645)
    -0.25
    (2.721)
    Pain Interference
    0.33
    (3.077)
    -0.18
    (3.082)
    5. Secondary Outcome
    Title Progression Free Survival (PFS) Rate at Specific Time-points
    Description PFS rate is defined as the proportion of participants experiencing PFS at the defined time-points.
    Time Frame From randomization to the specified time-point (up to 5 years)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants
    Arm/Group Title E-Ld Cohort Ld Cohort
    Arm/Group Description Participants receiving a combination of Elotuzumab (E) Lenalidomide (L) Dexamethasone (d) in a 28 day cycle Participants receiving a combination of Lenalidomide (L) Dexamethasone (d) in a 28 day cycle
    Measure Participants 374 374
    1 year
    0.77
    0.2%
    0.76
    0.2%
    2 year
    0.59
    0.2%
    0.55
    0.1%
    3 year
    0.46
    0.1%
    0.41
    0.1%
    4 year
    0.36
    0.1%
    0.33
    0.1%
    5 year
    0.26
    0.1%
    0.25
    0.1%

    Adverse Events

    Time Frame From first dose to 60 days after last dose
    Adverse Event Reporting Description
    Arm/Group Title E-Ld Cohort Ld Cohort
    Arm/Group Description Participants receiving a combination of Elotuzumab (E) Lenalidomide (L) Dexamethasone (d) in a 28 day cycle Participants receiving a combination of Lenalidomide (L) Dexamethasone (d) in a 28 day cycle
    All Cause Mortality
    E-Ld Cohort Ld Cohort
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 221/371 (59.6%) 215/371 (58%)
    Serious Adverse Events
    E-Ld Cohort Ld Cohort
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 292/371 (78.7%) 277/371 (74.7%)
    Blood and lymphatic system disorders
    Agranulocytosis 1/371 (0.3%) 0/371 (0%)
    Anaemia 12/371 (3.2%) 12/371 (3.2%)
    Febrile neutropenia 5/371 (1.3%) 3/371 (0.8%)
    Haemolysis 1/371 (0.3%) 0/371 (0%)
    Haemolytic anaemia 0/371 (0%) 1/371 (0.3%)
    Neutropenia 0/371 (0%) 1/371 (0.3%)
    Pancytopenia 4/371 (1.1%) 0/371 (0%)
    Plasmacytosis 0/371 (0%) 1/371 (0.3%)
    Thrombocytopenia 1/371 (0.3%) 2/371 (0.5%)
    Cardiac disorders
    Acute coronary syndrome 2/371 (0.5%) 2/371 (0.5%)
    Acute myocardial infarction 7/371 (1.9%) 0/371 (0%)
    Angina pectoris 2/371 (0.5%) 0/371 (0%)
    Aortic valve calcification 0/371 (0%) 1/371 (0.3%)
    Aortic valve incompetence 1/371 (0.3%) 0/371 (0%)
    Arrhythmia 1/371 (0.3%) 2/371 (0.5%)
    Atrial fibrillation 22/371 (5.9%) 12/371 (3.2%)
    Atrial flutter 3/371 (0.8%) 3/371 (0.8%)
    Atrial tachycardia 0/371 (0%) 2/371 (0.5%)
    Atrial thrombosis 1/371 (0.3%) 0/371 (0%)
    Atrioventricular block 0/371 (0%) 1/371 (0.3%)
    Bradycardia 1/371 (0.3%) 0/371 (0%)
    Cardiac arrest 6/371 (1.6%) 5/371 (1.3%)
    Cardiac failure 12/371 (3.2%) 7/371 (1.9%)
    Cardiac failure acute 1/371 (0.3%) 1/371 (0.3%)
    Cardiac failure chronic 1/371 (0.3%) 1/371 (0.3%)
    Cardiac failure congestive 4/371 (1.1%) 4/371 (1.1%)
    Cardiac septal hypertrophy 1/371 (0.3%) 0/371 (0%)
    Cardiac ventricular thrombosis 0/371 (0%) 1/371 (0.3%)
    Cardio-respiratory arrest 1/371 (0.3%) 1/371 (0.3%)
    Cardiogenic shock 1/371 (0.3%) 0/371 (0%)
    Cardiomyopathy 0/371 (0%) 1/371 (0.3%)
    Cardiopulmonary failure 0/371 (0%) 1/371 (0.3%)
    Cardiovascular disorder 2/371 (0.5%) 0/371 (0%)
    Congestive cardiomyopathy 0/371 (0%) 1/371 (0.3%)
    Coronary artery disease 2/371 (0.5%) 1/371 (0.3%)
    Left ventricular dysfunction 0/371 (0%) 2/371 (0.5%)
    Mitral valve incompetence 2/371 (0.5%) 0/371 (0%)
    Myocardial infarction 6/371 (1.6%) 5/371 (1.3%)
    Myocardial ischaemia 2/371 (0.5%) 1/371 (0.3%)
    Pericarditis 0/371 (0%) 1/371 (0.3%)
    Prinzmetal angina 1/371 (0.3%) 0/371 (0%)
    Sinus arrest 1/371 (0.3%) 0/371 (0%)
    Sinus node dysfunction 3/371 (0.8%) 1/371 (0.3%)
    Sinus tachycardia 0/371 (0%) 1/371 (0.3%)
    Supraventricular tachycardia 1/371 (0.3%) 0/371 (0%)
    Systolic dysfunction 1/371 (0.3%) 0/371 (0%)
    Tachycardia 2/371 (0.5%) 0/371 (0%)
    Torsade de pointes 1/371 (0.3%) 0/371 (0%)
    Ventricular arrhythmia 1/371 (0.3%) 1/371 (0.3%)
    Congenital, familial and genetic disorders
    Corneal dystrophy 1/371 (0.3%) 0/371 (0%)
    Ear and labyrinth disorders
    Sudden hearing loss 0/371 (0%) 1/371 (0.3%)
    Vertigo 0/371 (0%) 1/371 (0.3%)
    Eye disorders
    Blindness transient 1/371 (0.3%) 0/371 (0%)
    Cataract 10/371 (2.7%) 9/371 (2.4%)
    Cataract cortical 1/371 (0.3%) 0/371 (0%)
    Macular fibrosis 1/371 (0.3%) 0/371 (0%)
    Optic ischaemic neuropathy 1/371 (0.3%) 0/371 (0%)
    Retinal detachment 1/371 (0.3%) 0/371 (0%)
    Gastrointestinal disorders
    Abdominal pain 1/371 (0.3%) 2/371 (0.5%)
    Abdominal pain lower 0/371 (0%) 1/371 (0.3%)
    Abdominal pain upper 1/371 (0.3%) 1/371 (0.3%)
    Anal haemorrhage 0/371 (0%) 1/371 (0.3%)
    Anorectal varices haemorrhage 1/371 (0.3%) 0/371 (0%)
    Colitis 1/371 (0.3%) 1/371 (0.3%)
    Colitis ulcerative 0/371 (0%) 1/371 (0.3%)
    Constipation 3/371 (0.8%) 2/371 (0.5%)
    Diaphragmatic hernia 1/371 (0.3%) 0/371 (0%)
    Diarrhoea 9/371 (2.4%) 9/371 (2.4%)
    Diverticulum intestinal 1/371 (0.3%) 0/371 (0%)
    Duodenal ulcer 0/371 (0%) 1/371 (0.3%)
    Enteritis 1/371 (0.3%) 0/371 (0%)
    Enterovesical fistula 1/371 (0.3%) 0/371 (0%)
    Femoral hernia 1/371 (0.3%) 0/371 (0%)
    Gastritis 4/371 (1.1%) 0/371 (0%)
    Gastrointestinal haemorrhage 2/371 (0.5%) 1/371 (0.3%)
    Hiatus hernia 0/371 (0%) 1/371 (0.3%)
    Ileus 1/371 (0.3%) 2/371 (0.5%)
    Incarcerated inguinal hernia 1/371 (0.3%) 0/371 (0%)
    Incarcerated umbilical hernia 1/371 (0.3%) 0/371 (0%)
    Inguinal hernia 3/371 (0.8%) 2/371 (0.5%)
    Inguinal hernia strangulated 1/371 (0.3%) 0/371 (0%)
    Intestinal infarction 0/371 (0%) 1/371 (0.3%)
    Intestinal obstruction 4/371 (1.1%) 2/371 (0.5%)
    Intestinal perforation 0/371 (0%) 2/371 (0.5%)
    Large intestine polyp 0/371 (0%) 1/371 (0.3%)
    Lower gastrointestinal haemorrhage 0/371 (0%) 1/371 (0.3%)
    Melaena 1/371 (0.3%) 0/371 (0%)
    Nausea 0/371 (0%) 3/371 (0.8%)
    Odynophagia 0/371 (0%) 1/371 (0.3%)
    Oesophageal ulcer 1/371 (0.3%) 0/371 (0%)
    Oesophagitis 0/371 (0%) 1/371 (0.3%)
    Oroantral fistula 1/371 (0.3%) 0/371 (0%)
    Pancreatitis 0/371 (0%) 3/371 (0.8%)
    Pancreatitis acute 0/371 (0%) 1/371 (0.3%)
    Pneumatosis intestinalis 0/371 (0%) 1/371 (0.3%)
    Rectal haemorrhage 0/371 (0%) 2/371 (0.5%)
    Small intestinal obstruction 1/371 (0.3%) 1/371 (0.3%)
    Umbilical hernia 0/371 (0%) 1/371 (0.3%)
    Vomiting 3/371 (0.8%) 1/371 (0.3%)
    General disorders
    Adverse drug reaction 1/371 (0.3%) 0/371 (0%)
    Asthenia 3/371 (0.8%) 5/371 (1.3%)
    Chest pain 2/371 (0.5%) 4/371 (1.1%)
    Death 2/371 (0.5%) 3/371 (0.8%)
    Disease progression 8/371 (2.2%) 5/371 (1.3%)
    Fat necrosis 0/371 (0%) 1/371 (0.3%)
    Fatigue 2/371 (0.5%) 2/371 (0.5%)
    General physical health deterioration 3/371 (0.8%) 5/371 (1.3%)
    Inflammation 2/371 (0.5%) 0/371 (0%)
    Malaise 1/371 (0.3%) 0/371 (0%)
    Multiple organ dysfunction syndrome 1/371 (0.3%) 1/371 (0.3%)
    Non-cardiac chest pain 0/371 (0%) 3/371 (0.8%)
    Oedema 1/371 (0.3%) 1/371 (0.3%)
    Oedema peripheral 1/371 (0.3%) 4/371 (1.1%)
    Pain 1/371 (0.3%) 3/371 (0.8%)
    Performance status decreased 0/371 (0%) 1/371 (0.3%)
    Pyrexia 19/371 (5.1%) 7/371 (1.9%)
    Sudden cardiac death 1/371 (0.3%) 1/371 (0.3%)
    Sudden death 2/371 (0.5%) 1/371 (0.3%)
    Systemic inflammatory response syndrome 0/371 (0%) 1/371 (0.3%)
    Hepatobiliary disorders
    Bile duct obstruction 0/371 (0%) 1/371 (0.3%)
    Bile duct stone 1/371 (0.3%) 0/371 (0%)
    Cholecystitis 2/371 (0.5%) 1/371 (0.3%)
    Cholecystitis acute 2/371 (0.5%) 0/371 (0%)
    Cholecystitis chronic 0/371 (0%) 1/371 (0.3%)
    Cholelithiasis 0/371 (0%) 1/371 (0.3%)
    Gallbladder rupture 1/371 (0.3%) 0/371 (0%)
    Hydrocholecystis 0/371 (0%) 1/371 (0.3%)
    Jaundice 1/371 (0.3%) 0/371 (0%)
    Immune system disorders
    Drug hypersensitivity 0/371 (0%) 1/371 (0.3%)
    Hypersensitivity 2/371 (0.5%) 0/371 (0%)
    Infections and infestations
    Abdominal abscess 0/371 (0%) 1/371 (0.3%)
    Abscess 0/371 (0%) 1/371 (0.3%)
    Abscess limb 1/371 (0.3%) 0/371 (0%)
    Appendicitis 1/371 (0.3%) 0/371 (0%)
    Bacteraemia 1/371 (0.3%) 1/371 (0.3%)
    Bacterial prostatitis 0/371 (0%) 1/371 (0.3%)
    Biliary sepsis 1/371 (0.3%) 0/371 (0%)
    Bronchiolitis 1/371 (0.3%) 0/371 (0%)
    Bronchitis 18/371 (4.9%) 6/371 (1.6%)
    Bursitis infective 1/371 (0.3%) 0/371 (0%)
    Cellulitis 9/371 (2.4%) 8/371 (2.2%)
    Cellulitis orbital 1/371 (0.3%) 1/371 (0.3%)
    Central nervous system infection 1/371 (0.3%) 0/371 (0%)
    Clostridium colitis 1/371 (0.3%) 0/371 (0%)
    Clostridium difficile colitis 2/371 (0.5%) 1/371 (0.3%)
    Clostridium difficile infection 1/371 (0.3%) 1/371 (0.3%)
    Dacryocystitis 1/371 (0.3%) 0/371 (0%)
    Device related infection 1/371 (0.3%) 1/371 (0.3%)
    Diverticulitis 5/371 (1.3%) 3/371 (0.8%)
    Erysipelas 2/371 (0.5%) 1/371 (0.3%)
    Escherichia bacteraemia 0/371 (0%) 2/371 (0.5%)
    Escherichia infection 1/371 (0.3%) 0/371 (0%)
    Escherichia urinary tract infection 1/371 (0.3%) 1/371 (0.3%)
    Febrile infection 2/371 (0.5%) 0/371 (0%)
    Gastroenteritis 8/371 (2.2%) 2/371 (0.5%)
    Gastroenteritis clostridial 1/371 (0.3%) 0/371 (0%)
    Gastroenteritis salmonella 1/371 (0.3%) 0/371 (0%)
    Gastroenteritis viral 0/371 (0%) 1/371 (0.3%)
    Gastrointestinal infection 1/371 (0.3%) 0/371 (0%)
    H1N1 influenza 0/371 (0%) 1/371 (0.3%)
    Hepatitis E 1/371 (0.3%) 0/371 (0%)
    Herpes zoster 0/371 (0%) 2/371 (0.5%)
    Herpes zoster disseminated 0/371 (0%) 1/371 (0.3%)
    Infected cyst 1/371 (0.3%) 0/371 (0%)
    Infection 4/371 (1.1%) 1/371 (0.3%)
    Infectious pleural effusion 1/371 (0.3%) 0/371 (0%)
    Influenza 7/371 (1.9%) 6/371 (1.6%)
    Intervertebral discitis 1/371 (0.3%) 0/371 (0%)
    Large intestine infection 0/371 (0%) 1/371 (0.3%)
    Leishmaniasis 1/371 (0.3%) 0/371 (0%)
    Liver abscess 1/371 (0.3%) 0/371 (0%)
    Localised infection 1/371 (0.3%) 0/371 (0%)
    Lower respiratory tract infection 8/371 (2.2%) 7/371 (1.9%)
    Meningitis listeria 1/371 (0.3%) 1/371 (0.3%)
    Metapneumovirus infection 1/371 (0.3%) 1/371 (0.3%)
    Neutropenic sepsis 1/371 (0.3%) 0/371 (0%)
    Orchitis 0/371 (0%) 1/371 (0.3%)
    Perirectal abscess 1/371 (0.3%) 1/371 (0.3%)
    Peritonitis 1/371 (0.3%) 0/371 (0%)
    Pharyngitis 1/371 (0.3%) 0/371 (0%)
    Plague 1/371 (0.3%) 0/371 (0%)
    Pleural infection 0/371 (0%) 1/371 (0.3%)
    Pneumococcal sepsis 1/371 (0.3%) 0/371 (0%)
    Pneumocystis jirovecii pneumonia 2/371 (0.5%) 0/371 (0%)
    Pneumonia 60/371 (16.2%) 48/371 (12.9%)
    Pneumonia bacterial 1/371 (0.3%) 1/371 (0.3%)
    Pneumonia cytomegaloviral 1/371 (0.3%) 0/371 (0%)
    Pneumonia fungal 2/371 (0.5%) 0/371 (0%)
    Pneumonia influenzal 1/371 (0.3%) 0/371 (0%)
    Pneumonia legionella 0/371 (0%) 1/371 (0.3%)
    Pneumonia staphylococcal 1/371 (0.3%) 0/371 (0%)
    Pneumonia streptococcal 1/371 (0.3%) 0/371 (0%)
    Pneumonia viral 0/371 (0%) 1/371 (0.3%)
    Progressive multifocal leukoencephalopathy 0/371 (0%) 1/371 (0.3%)
    Pseudomembranous colitis 1/371 (0.3%) 0/371 (0%)
    Pyelonephritis 1/371 (0.3%) 2/371 (0.5%)
    Pyoderma 1/371 (0.3%) 0/371 (0%)
    Respiratory syncytial virus infection 0/371 (0%) 1/371 (0.3%)
    Respiratory tract infection 8/371 (2.2%) 3/371 (0.8%)
    Sepsis 15/371 (4%) 6/371 (1.6%)
    Septic shock 4/371 (1.1%) 6/371 (1.6%)
    Staphylococcal infection 2/371 (0.5%) 0/371 (0%)
    Staphylococcal sepsis 1/371 (0.3%) 0/371 (0%)
    Subcutaneous abscess 0/371 (0%) 1/371 (0.3%)
    Upper respiratory tract infection 5/371 (1.3%) 4/371 (1.1%)
    Urinary tract infection 15/371 (4%) 11/371 (3%)
    Urinary tract infection bacterial 0/371 (0%) 1/371 (0.3%)
    Urinary tract infection enterococcal 1/371 (0.3%) 0/371 (0%)
    Urosepsis 4/371 (1.1%) 5/371 (1.3%)
    Varicella zoster virus infection 1/371 (0.3%) 0/371 (0%)
    Vascular device infection 1/371 (0.3%) 0/371 (0%)
    Viral infection 1/371 (0.3%) 1/371 (0.3%)
    Whipple's disease 1/371 (0.3%) 0/371 (0%)
    Wound infection staphylococcal 1/371 (0.3%) 0/371 (0%)
    Injury, poisoning and procedural complications
    Accidental overdose 0/371 (0%) 1/371 (0.3%)
    Comminuted fracture 0/371 (0%) 1/371 (0.3%)
    Extradural haematoma 0/371 (0%) 1/371 (0.3%)
    Fall 2/371 (0.5%) 2/371 (0.5%)
    Femoral neck fracture 0/371 (0%) 2/371 (0.5%)
    Femur fracture 4/371 (1.1%) 8/371 (2.2%)
    Fibula fracture 0/371 (0%) 2/371 (0.5%)
    Fracture 3/371 (0.8%) 0/371 (0%)
    Hip fracture 5/371 (1.3%) 4/371 (1.1%)
    Humerus fracture 1/371 (0.3%) 1/371 (0.3%)
    Infusion related reaction 1/371 (0.3%) 0/371 (0%)
    Joint injury 1/371 (0.3%) 0/371 (0%)
    Lower limb fracture 0/371 (0%) 1/371 (0.3%)
    Lumbar vertebral fracture 0/371 (0%) 1/371 (0.3%)
    Medication error 1/371 (0.3%) 0/371 (0%)
    Overdose 2/371 (0.5%) 0/371 (0%)
    Pelvic fracture 1/371 (0.3%) 1/371 (0.3%)
    Post procedural complication 1/371 (0.3%) 0/371 (0%)
    Pubis fracture 0/371 (0%) 1/371 (0.3%)
    Rib fracture 1/371 (0.3%) 4/371 (1.1%)
    Shunt malfunction 0/371 (0%) 1/371 (0.3%)
    Skin laceration 1/371 (0.3%) 1/371 (0.3%)
    Spinal compression fracture 2/371 (0.5%) 4/371 (1.1%)
    Spinal fracture 2/371 (0.5%) 3/371 (0.8%)
    Stress fracture 0/371 (0%) 1/371 (0.3%)
    Subdural haematoma 1/371 (0.3%) 2/371 (0.5%)
    Thoracic vertebral fracture 1/371 (0.3%) 1/371 (0.3%)
    Tibia fracture 0/371 (0%) 2/371 (0.5%)
    Traumatic fracture 0/371 (0%) 2/371 (0.5%)
    Upper limb fracture 0/371 (0%) 1/371 (0.3%)
    Wrist fracture 1/371 (0.3%) 0/371 (0%)
    Investigations
    Alanine aminotransferase increased 1/371 (0.3%) 0/371 (0%)
    Aspartate aminotransferase increased 1/371 (0.3%) 0/371 (0%)
    Bacterial test positive 1/371 (0.3%) 1/371 (0.3%)
    Blood creatinine increased 2/371 (0.5%) 2/371 (0.5%)
    Haemoglobin decreased 1/371 (0.3%) 0/371 (0%)
    Hepatic enzyme increased 1/371 (0.3%) 0/371 (0%)
    Influenza A virus test positive 1/371 (0.3%) 0/371 (0%)
    Influenza B virus test positive 1/371 (0.3%) 0/371 (0%)
    Liver function test abnormal 1/371 (0.3%) 0/371 (0%)
    Respiratory syncytial virus test positive 1/371 (0.3%) 0/371 (0%)
    Respirovirus test positive 0/371 (0%) 1/371 (0.3%)
    Transaminases increased 0/371 (0%) 2/371 (0.5%)
    Viral test positive 1/371 (0.3%) 0/371 (0%)
    Weight decreased 1/371 (0.3%) 1/371 (0.3%)
    Metabolism and nutrition disorders
    Alcohol intolerance 1/371 (0.3%) 0/371 (0%)
    Decreased appetite 1/371 (0.3%) 0/371 (0%)
    Dehydration 7/371 (1.9%) 5/371 (1.3%)
    Diabetic complication 0/371 (0%) 1/371 (0.3%)
    Diabetic ketoacidosis 0/371 (0%) 1/371 (0.3%)
    Diabetic metabolic decompensation 0/371 (0%) 1/371 (0.3%)
    Electrolyte imbalance 1/371 (0.3%) 2/371 (0.5%)
    Failure to thrive 1/371 (0.3%) 2/371 (0.5%)
    Fluid overload 0/371 (0%) 1/371 (0.3%)
    Gout 1/371 (0.3%) 0/371 (0%)
    Hypercalcaemia 2/371 (0.5%) 5/371 (1.3%)
    Hyperglycaemia 3/371 (0.8%) 2/371 (0.5%)
    Hypoalbuminaemia 1/371 (0.3%) 1/371 (0.3%)
    Hypocalcaemia 4/371 (1.1%) 4/371 (1.1%)
    Hypoglycaemia 5/371 (1.3%) 1/371 (0.3%)
    Hypokalaemia 4/371 (1.1%) 1/371 (0.3%)
    Hypomagnesaemia 4/371 (1.1%) 0/371 (0%)
    Hyponatraemia 2/371 (0.5%) 1/371 (0.3%)
    Hypophosphataemia 1/371 (0.3%) 0/371 (0%)
    Malnutrition 0/371 (0%) 1/371 (0.3%)
    Tumour lysis syndrome 1/371 (0.3%) 1/371 (0.3%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/371 (0.3%) 2/371 (0.5%)
    Arthritis 0/371 (0%) 1/371 (0.3%)
    Arthritis reactive 1/371 (0.3%) 0/371 (0%)
    Back pain 11/371 (3%) 9/371 (2.4%)
    Bone pain 3/371 (0.8%) 4/371 (1.1%)
    Bursitis 0/371 (0%) 1/371 (0.3%)
    Chondrocalcinosis 1/371 (0.3%) 0/371 (0%)
    Chondrocalcinosis pyrophosphate 1/371 (0.3%) 0/371 (0%)
    Flank pain 0/371 (0%) 1/371 (0.3%)
    Intervertebral disc protrusion 1/371 (0.3%) 0/371 (0%)
    Joint hyperextension 1/371 (0.3%) 0/371 (0%)
    Muscle contracture 0/371 (0%) 1/371 (0.3%)
    Muscular weakness 1/371 (0.3%) 1/371 (0.3%)
    Musculoskeletal chest pain 0/371 (0%) 1/371 (0.3%)
    Musculoskeletal disorder 1/371 (0.3%) 0/371 (0%)
    Musculoskeletal pain 1/371 (0.3%) 1/371 (0.3%)
    Osteitis 1/371 (0.3%) 0/371 (0%)
    Osteoarthritis 3/371 (0.8%) 0/371 (0%)
    Osteonecrosis 2/371 (0.5%) 0/371 (0%)
    Osteonecrosis of jaw 3/371 (0.8%) 2/371 (0.5%)
    Pain in extremity 1/371 (0.3%) 2/371 (0.5%)
    Pathological fracture 1/371 (0.3%) 1/371 (0.3%)
    Spinal pain 3/371 (0.8%) 1/371 (0.3%)
    Spinal stenosis 0/371 (0%) 1/371 (0.3%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute lymphocytic leukaemia 0/371 (0%) 2/371 (0.5%)
    Adenocarcinoma 1/371 (0.3%) 0/371 (0%)
    Angiosarcoma 1/371 (0.3%) 0/371 (0%)
    Atypical fibroxanthoma 1/371 (0.3%) 0/371 (0%)
    Basal cell carcinoma 10/371 (2.7%) 8/371 (2.2%)
    Basosquamous carcinoma 0/371 (0%) 1/371 (0.3%)
    Bladder neoplasm 0/371 (0%) 1/371 (0.3%)
    Bowen's disease 0/371 (0%) 1/371 (0.3%)
    Cholangiocarcinoma 1/371 (0.3%) 1/371 (0.3%)
    Colon cancer 1/371 (0.3%) 0/371 (0%)
    Colon cancer metastatic 0/371 (0%) 1/371 (0.3%)
    Gastric cancer 0/371 (0%) 1/371 (0.3%)
    Hepatic cancer 1/371 (0.3%) 0/371 (0%)
    Hepatocellular carcinoma 1/371 (0.3%) 0/371 (0%)
    Intraductal proliferative breast lesion 1/371 (0.3%) 0/371 (0%)
    Keratoacanthoma 1/371 (0.3%) 1/371 (0.3%)
    Laryngeal cancer 1/371 (0.3%) 0/371 (0%)
    Laryngeal squamous cell carcinoma 1/371 (0.3%) 0/371 (0%)
    Lip squamous cell carcinoma 0/371 (0%) 1/371 (0.3%)
    Lung adenocarcinoma 0/371 (0%) 2/371 (0.5%)
    Malignant melanoma 1/371 (0.3%) 1/371 (0.3%)
    Malignant melanoma in situ 0/371 (0%) 2/371 (0.5%)
    Myelodysplastic syndrome 1/371 (0.3%) 0/371 (0%)
    Nasal cavity cancer 0/371 (0%) 1/371 (0.3%)
    Pancreatic carcinoma 1/371 (0.3%) 0/371 (0%)
    Papilloma 1/371 (0.3%) 0/371 (0%)
    Plasma cell leukaemia 1/371 (0.3%) 0/371 (0%)
    Plasma cell myeloma 5/371 (1.3%) 3/371 (0.8%)
    Plasmacytoma 1/371 (0.3%) 0/371 (0%)
    Prostate cancer 5/371 (1.3%) 0/371 (0%)
    Rectal cancer 1/371 (0.3%) 0/371 (0%)
    Rectosigmoid cancer 1/371 (0.3%) 0/371 (0%)
    Refractory anaemia with ringed sideroblasts 1/371 (0.3%) 0/371 (0%)
    Sebaceous carcinoma 0/371 (0%) 1/371 (0.3%)
    Spindle cell sarcoma 1/371 (0.3%) 0/371 (0%)
    Squamous cell carcinoma 15/371 (4%) 12/371 (3.2%)
    Squamous cell carcinoma of head and neck 1/371 (0.3%) 0/371 (0%)
    Squamous cell carcinoma of skin 7/371 (1.9%) 5/371 (1.3%)
    Squamous cell carcinoma of the oral cavity 1/371 (0.3%) 0/371 (0%)
    Transitional cell carcinoma 1/371 (0.3%) 0/371 (0%)
    Nervous system disorders
    Ataxia 1/371 (0.3%) 0/371 (0%)
    Carotid artery stenosis 1/371 (0.3%) 1/371 (0.3%)
    Cerebellar haemorrhage 1/371 (0.3%) 0/371 (0%)
    Cerebral haemorrhage 1/371 (0.3%) 3/371 (0.8%)
    Cerebral infarction 2/371 (0.5%) 2/371 (0.5%)
    Cerebral ischaemia 3/371 (0.8%) 2/371 (0.5%)
    Cerebrovascular accident 8/371 (2.2%) 7/371 (1.9%)
    Cognitive disorder 1/371 (0.3%) 1/371 (0.3%)
    Coma 1/371 (0.3%) 0/371 (0%)
    Dementia 1/371 (0.3%) 0/371 (0%)
    Depressed level of consciousness 1/371 (0.3%) 0/371 (0%)
    Dizziness 1/371 (0.3%) 1/371 (0.3%)
    Dizziness postural 0/371 (0%) 1/371 (0.3%)
    Dysarthria 2/371 (0.5%) 0/371 (0%)
    Encephalopathy 1/371 (0.3%) 0/371 (0%)
    Generalised tonic-clonic seizure 0/371 (0%) 1/371 (0.3%)
    Guillain-Barre syndrome 1/371 (0.3%) 1/371 (0.3%)
    Haemorrhage intracranial 1/371 (0.3%) 0/371 (0%)
    Haemorrhagic cerebral infarction 0/371 (0%) 1/371 (0.3%)
    Haemorrhagic stroke 0/371 (0%) 1/371 (0.3%)
    Headache 1/371 (0.3%) 1/371 (0.3%)
    Intracranial aneurysm 1/371 (0.3%) 0/371 (0%)
    Intracranial haematoma 0/371 (0%) 1/371 (0.3%)
    Ischaemic cerebral infarction 0/371 (0%) 1/371 (0.3%)
    Ischaemic stroke 3/371 (0.8%) 1/371 (0.3%)
    Lethargy 0/371 (0%) 1/371 (0.3%)
    Loss of consciousness 1/371 (0.3%) 1/371 (0.3%)
    Memory impairment 0/371 (0%) 1/371 (0.3%)
    Metabolic encephalopathy 0/371 (0%) 1/371 (0.3%)
    Migraine 1/371 (0.3%) 0/371 (0%)
    Myelopathy 1/371 (0.3%) 0/371 (0%)
    Normal pressure hydrocephalus 0/371 (0%) 1/371 (0.3%)
    Presyncope 2/371 (0.5%) 0/371 (0%)
    Sciatica 1/371 (0.3%) 0/371 (0%)
    Somnolence 1/371 (0.3%) 0/371 (0%)
    Spinal cord compression 0/371 (0%) 1/371 (0.3%)
    Subarachnoid haemorrhage 2/371 (0.5%) 0/371 (0%)
    Syncope 7/371 (1.9%) 5/371 (1.3%)
    Transient aphasia 1/371 (0.3%) 0/371 (0%)
    Transient ischaemic attack 6/371 (1.6%) 4/371 (1.1%)
    Product Issues
    Device dislocation 2/371 (0.5%) 0/371 (0%)
    Psychiatric disorders
    Anxiety 0/371 (0%) 2/371 (0.5%)
    Completed suicide 1/371 (0.3%) 0/371 (0%)
    Confusional state 5/371 (1.3%) 5/371 (1.3%)
    Delirium 2/371 (0.5%) 0/371 (0%)
    Delusional disorder, unspecified type 1/371 (0.3%) 0/371 (0%)
    Depression 2/371 (0.5%) 0/371 (0%)
    Mental status changes 1/371 (0.3%) 1/371 (0.3%)
    Psychotic disorder 1/371 (0.3%) 1/371 (0.3%)
    Renal and urinary disorders
    Acute kidney injury 20/371 (5.4%) 20/371 (5.4%)
    Calculus urinary 0/371 (0%) 1/371 (0.3%)
    Chronic kidney disease 2/371 (0.5%) 0/371 (0%)
    End stage renal disease 1/371 (0.3%) 0/371 (0%)
    Haematuria 1/371 (0.3%) 2/371 (0.5%)
    Myeloma cast nephropathy 0/371 (0%) 1/371 (0.3%)
    Nephrolithiasis 1/371 (0.3%) 2/371 (0.5%)
    Renal failure 10/371 (2.7%) 7/371 (1.9%)
    Renal impairment 1/371 (0.3%) 3/371 (0.8%)
    Renal injury 1/371 (0.3%) 0/371 (0%)
    Renal tubular necrosis 1/371 (0.3%) 0/371 (0%)
    Urinary retention 2/371 (0.5%) 0/371 (0%)
    Urinary tract disorder 0/371 (0%) 1/371 (0.3%)
    Reproductive system and breast disorders
    Endometrial hyperplasia 0/371 (0%) 1/371 (0.3%)
    Uterine prolapse 1/371 (0.3%) 0/371 (0%)
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema 2/371 (0.5%) 0/371 (0%)
    Acute respiratory failure 3/371 (0.8%) 0/371 (0%)
    Bronchiectasis 1/371 (0.3%) 1/371 (0.3%)
    Bronchopneumopathy 1/371 (0.3%) 0/371 (0%)
    Bronchospasm 1/371 (0.3%) 0/371 (0%)
    Chronic obstructive pulmonary disease 3/371 (0.8%) 6/371 (1.6%)
    Cough 1/371 (0.3%) 0/371 (0%)
    Dyspnoea 12/371 (3.2%) 8/371 (2.2%)
    Epistaxis 1/371 (0.3%) 0/371 (0%)
    Hypoxia 0/371 (0%) 2/371 (0.5%)
    Interstitial lung disease 3/371 (0.8%) 3/371 (0.8%)
    Pleural effusion 5/371 (1.3%) 3/371 (0.8%)
    Pleuritic pain 0/371 (0%) 1/371 (0.3%)
    Pneumonia aspiration 5/371 (1.3%) 0/371 (0%)
    Pneumonitis 1/371 (0.3%) 4/371 (1.1%)
    Pneumothorax 0/371 (0%) 1/371 (0.3%)
    Pulmonary congestion 0/371 (0%) 1/371 (0.3%)
    Pulmonary embolism 12/371 (3.2%) 15/371 (4%)
    Pulmonary oedema 3/371 (0.8%) 4/371 (1.1%)
    Respiratory depression 1/371 (0.3%) 0/371 (0%)
    Respiratory disorder 1/371 (0.3%) 0/371 (0%)
    Respiratory distress 2/371 (0.5%) 1/371 (0.3%)
    Respiratory failure 4/371 (1.1%) 2/371 (0.5%)
    Restrictive pulmonary disease 1/371 (0.3%) 0/371 (0%)
    Sinus disorder 1/371 (0.3%) 0/371 (0%)
    Vocal cord disorder 1/371 (0.3%) 0/371 (0%)
    Skin and subcutaneous tissue disorders
    Actinic keratosis 1/371 (0.3%) 0/371 (0%)
    Angioedema 0/371 (0%) 1/371 (0.3%)
    Cold sweat 0/371 (0%) 1/371 (0.3%)
    Cutaneous vasculitis 1/371 (0.3%) 0/371 (0%)
    Dermatitis bullous 1/371 (0.3%) 0/371 (0%)
    Dermatitis exfoliative generalised 0/371 (0%) 1/371 (0.3%)
    Diabetic foot 0/371 (0%) 1/371 (0.3%)
    Erythema 0/371 (0%) 1/371 (0.3%)
    Exfoliative rash 0/371 (0%) 2/371 (0.5%)
    Hypersensitivity vasculitis 0/371 (0%) 1/371 (0.3%)
    Purpura 0/371 (0%) 1/371 (0.3%)
    Rash 1/371 (0.3%) 1/371 (0.3%)
    Rash maculo-papular 1/371 (0.3%) 0/371 (0%)
    Skin ulcer 0/371 (0%) 1/371 (0.3%)
    Stasis dermatitis 1/371 (0.3%) 0/371 (0%)
    Stevens-Johnson syndrome 1/371 (0.3%) 0/371 (0%)
    Subcutaneous emphysema 0/371 (0%) 1/371 (0.3%)
    Vascular disorders
    Aortic aneurysm 1/371 (0.3%) 2/371 (0.5%)
    Arteriosclerosis 0/371 (0%) 1/371 (0.3%)
    Circulatory collapse 1/371 (0.3%) 1/371 (0.3%)
    Deep vein thrombosis 9/371 (2.4%) 10/371 (2.7%)
    Embolism 3/371 (0.8%) 0/371 (0%)
    Embolism venous 0/371 (0%) 1/371 (0.3%)
    Haematoma 0/371 (0%) 1/371 (0.3%)
    Hypertension 1/371 (0.3%) 2/371 (0.5%)
    Hypotension 6/371 (1.6%) 2/371 (0.5%)
    Hypovolaemic shock 1/371 (0.3%) 0/371 (0%)
    Malignant hypertension 1/371 (0.3%) 0/371 (0%)
    Orthostatic hypotension 1/371 (0.3%) 0/371 (0%)
    Peripheral artery thrombosis 0/371 (0%) 1/371 (0.3%)
    Peripheral ischaemia 0/371 (0%) 1/371 (0.3%)
    Thrombophlebitis 2/371 (0.5%) 0/371 (0%)
    Thrombophlebitis superficial 0/371 (0%) 1/371 (0.3%)
    Thrombosis 0/371 (0%) 1/371 (0.3%)
    Venous thrombosis 0/371 (0%) 1/371 (0.3%)
    Other (Not Including Serious) Adverse Events
    E-Ld Cohort Ld Cohort
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 369/371 (99.5%) 368/371 (99.2%)
    Blood and lymphatic system disorders
    Anaemia 151/371 (40.7%) 159/371 (42.9%)
    Leukopenia 23/371 (6.2%) 37/371 (10%)
    Neutropenia 94/371 (25.3%) 117/371 (31.5%)
    Thrombocytopenia 66/371 (17.8%) 69/371 (18.6%)
    Cardiac disorders
    Atrial fibrillation 28/371 (7.5%) 25/371 (6.7%)
    Eye disorders
    Cataract 61/371 (16.4%) 56/371 (15.1%)
    Vision blurred 28/371 (7.5%) 28/371 (7.5%)
    Gastrointestinal disorders
    Abdominal pain 50/371 (13.5%) 50/371 (13.5%)
    Abdominal pain upper 33/371 (8.9%) 29/371 (7.8%)
    Constipation 141/371 (38%) 144/371 (38.8%)
    Diarrhoea 192/371 (51.8%) 178/371 (48%)
    Dry mouth 28/371 (7.5%) 26/371 (7%)
    Dyspepsia 43/371 (11.6%) 30/371 (8.1%)
    Haemorrhoids 9/371 (2.4%) 19/371 (5.1%)
    Nausea 117/371 (31.5%) 107/371 (28.8%)
    Toothache 24/371 (6.5%) 15/371 (4%)
    Vomiting 69/371 (18.6%) 48/371 (12.9%)
    General disorders
    Asthenia 88/371 (23.7%) 72/371 (19.4%)
    Chest pain 24/371 (6.5%) 32/371 (8.6%)
    Chills 35/371 (9.4%) 9/371 (2.4%)
    Fatigue 182/371 (49.1%) 186/371 (50.1%)
    Influenza like illness 39/371 (10.5%) 28/371 (7.5%)
    Mucosal inflammation 21/371 (5.7%) 7/371 (1.9%)
    Oedema 17/371 (4.6%) 20/371 (5.4%)
    Oedema peripheral 162/371 (43.7%) 181/371 (48.8%)
    Pain 25/371 (6.7%) 19/371 (5.1%)
    Peripheral swelling 24/371 (6.5%) 23/371 (6.2%)
    Pyrexia 111/371 (29.9%) 77/371 (20.8%)
    Infections and infestations
    Bronchitis 45/371 (12.1%) 52/371 (14%)
    Cellulitis 20/371 (5.4%) 26/371 (7%)
    Cystitis 13/371 (3.5%) 19/371 (5.1%)
    Herpes zoster 23/371 (6.2%) 18/371 (4.9%)
    Influenza 14/371 (3.8%) 21/371 (5.7%)
    Nasopharyngitis 60/371 (16.2%) 62/371 (16.7%)
    Oral herpes 23/371 (6.2%) 11/371 (3%)
    Pneumonia 33/371 (8.9%) 23/371 (6.2%)
    Respiratory tract infection 38/371 (10.2%) 34/371 (9.2%)
    Sinusitis 22/371 (5.9%) 17/371 (4.6%)
    Upper respiratory tract infection 81/371 (21.8%) 83/371 (22.4%)
    Urinary tract infection 58/371 (15.6%) 56/371 (15.1%)
    Injury, poisoning and procedural complications
    Contusion 47/371 (12.7%) 53/371 (14.3%)
    Fall 30/371 (8.1%) 32/371 (8.6%)
    Skin abrasion 22/371 (5.9%) 13/371 (3.5%)
    Skin laceration 19/371 (5.1%) 22/371 (5.9%)
    Investigations
    Alanine aminotransferase increased 18/371 (4.9%) 27/371 (7.3%)
    Aspartate aminotransferase increased 17/371 (4.6%) 21/371 (5.7%)
    Blood creatinine increased 54/371 (14.6%) 72/371 (19.4%)
    Glomerular filtration rate decreased 20/371 (5.4%) 17/371 (4.6%)
    Neutrophil count decreased 9/371 (2.4%) 28/371 (7.5%)
    Platelet count decreased 12/371 (3.2%) 20/371 (5.4%)
    Weight decreased 77/371 (20.8%) 66/371 (17.8%)
    Metabolism and nutrition disorders
    Decreased appetite 100/371 (27%) 85/371 (22.9%)
    Dehydration 25/371 (6.7%) 22/371 (5.9%)
    Hyperglycaemia 120/371 (32.3%) 69/371 (18.6%)
    Hypoalbuminaemia 24/371 (6.5%) 21/371 (5.7%)
    Hypocalcaemia 73/371 (19.7%) 75/371 (20.2%)
    Hypokalaemia 84/371 (22.6%) 90/371 (24.3%)
    Hypomagnesaemia 40/371 (10.8%) 23/371 (6.2%)
    Hyponatraemia 27/371 (7.3%) 17/371 (4.6%)
    Hypophosphataemia 20/371 (5.4%) 16/371 (4.3%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 94/371 (25.3%) 100/371 (27%)
    Back pain 135/371 (36.4%) 135/371 (36.4%)
    Bone pain 58/371 (15.6%) 56/371 (15.1%)
    Joint swelling 19/371 (5.1%) 16/371 (4.3%)
    Muscle spasms 84/371 (22.6%) 83/371 (22.4%)
    Muscular weakness 45/371 (12.1%) 52/371 (14%)
    Musculoskeletal chest pain 49/371 (13.2%) 48/371 (12.9%)
    Musculoskeletal pain 70/371 (18.9%) 65/371 (17.5%)
    Myalgia 21/371 (5.7%) 18/371 (4.9%)
    Neck pain 30/371 (8.1%) 38/371 (10.2%)
    Pain in extremity 74/371 (19.9%) 76/371 (20.5%)
    Pain in jaw 19/371 (5.1%) 12/371 (3.2%)
    Spinal pain 14/371 (3.8%) 21/371 (5.7%)
    Nervous system disorders
    Dizziness 83/371 (22.4%) 66/371 (17.8%)
    Dysgeusia 26/371 (7%) 13/371 (3.5%)
    Headache 61/371 (16.4%) 49/371 (13.2%)
    Hypoaesthesia 24/371 (6.5%) 25/371 (6.7%)
    Memory impairment 26/371 (7%) 15/371 (4%)
    Neuropathy peripheral 42/371 (11.3%) 48/371 (12.9%)
    Paraesthesia 39/371 (10.5%) 45/371 (12.1%)
    Peripheral sensory neuropathy 57/371 (15.4%) 59/371 (15.9%)
    Syncope 17/371 (4.6%) 20/371 (5.4%)
    Taste disorder 24/371 (6.5%) 27/371 (7.3%)
    Tremor 61/371 (16.4%) 55/371 (14.8%)
    Psychiatric disorders
    Agitation 21/371 (5.7%) 17/371 (4.6%)
    Anxiety 44/371 (11.9%) 28/371 (7.5%)
    Confusional state 36/371 (9.7%) 31/371 (8.4%)
    Depression 41/371 (11.1%) 31/371 (8.4%)
    Insomnia 98/371 (26.4%) 95/371 (25.6%)
    Mood altered 25/371 (6.7%) 17/371 (4.6%)
    Respiratory, thoracic and mediastinal disorders
    Cough 119/371 (32.1%) 106/371 (28.6%)
    Dysphonia 45/371 (12.1%) 27/371 (7.3%)
    Dyspnoea 87/371 (23.5%) 93/371 (25.1%)
    Dyspnoea exertional 24/371 (6.5%) 18/371 (4.9%)
    Epistaxis 27/371 (7.3%) 18/371 (4.9%)
    Oropharyngeal pain 25/371 (6.7%) 26/371 (7%)
    Productive cough 33/371 (8.9%) 20/371 (5.4%)
    Skin and subcutaneous tissue disorders
    Dry skin 27/371 (7.3%) 20/371 (5.4%)
    Erythema 19/371 (5.1%) 24/371 (6.5%)
    Hyperhidrosis 35/371 (9.4%) 26/371 (7%)
    Night sweats 24/371 (6.5%) 15/371 (4%)
    Pruritus 40/371 (10.8%) 44/371 (11.9%)
    Rash 90/371 (24.3%) 87/371 (23.5%)
    Skin lesion 20/371 (5.4%) 15/371 (4%)
    Vascular disorders
    Deep vein thrombosis 20/371 (5.4%) 27/371 (7.3%)
    Flushing 19/371 (5.1%) 17/371 (4.6%)
    Hypertension 53/371 (14.3%) 44/371 (11.9%)
    Hypotension 63/371 (17%) 44/371 (11.9%)

    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.

    Results Point of Contact

    Name/Title Bristol-Myers Squibb Study Director
    Organization Bristol-Myers Squibb
    Phone Please email
    Email Clinical.Trials@bms.com
    Responsible Party:
    Bristol-Myers Squibb
    ClinicalTrials.gov Identifier:
    NCT01335399
    Other Study ID Numbers:
    • CA204-006
    • 2010-022445-20
    First Posted:
    Apr 14, 2011
    Last Update Posted:
    Jul 20, 2022
    Last Verified:
    Jul 1, 2022