Phase 1b Study of Weekly Carfilzomib in Combination With... | NCT02335983

Label	Type	Description	Intervention Names
RRMM Dose-evaluation: Carfilzomib 56 mg/m²	Experimental	Participants with relapsed or refractory multiple myeloma (RRMM) received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 56 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.	Drug: Carfilzomib Drug: Lenalidomide Drug: Dexamethasone
RRMM Dose-evaluation: Carfilzomib 70 mg/m²	Experimental	Participants with RRMM received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 70 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.	Drug: Carfilzomib Drug: Lenalidomide Drug: Dexamethasone
RRMM Dose-expansion: Carfilzomib 70 mg/m²	Experimental	Participants with RRMM received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 70 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.

Name	Type	Description	Arm Group Labels	Other Names
Carfilzomib	Drug	Administered once weekly by 30-minute intravenous (IV) infusion on days 1, 8, and 15 of each 28-day cycle.	NDMM Dose-evaluation: Carfilzomib 56/70 mg/m²

Measure	Description	Time Frame
Number of Participants With Adverse Events (AEs)	Safety and tolerability were evaluated according to the type, incidence, and severity of adverse events. An AE is defined as any untoward medical occurrence in a clinical trial subject. The event does not necessarily have a causal relationship with study treatment. A serious adverse event is defined as an AE that meets at least 1 of the following serious criteria: fatal life threatening requires in-patient hospitalization or prolongation of existing hospitalization results in persistent or significant disability/incapacity congenital anomaly/birth defect other medically important serious event The severity of each AE was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03 where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death.	From the first dose of any study drug up to 30 days after the last dose of any study drug; median (range) duration of treatment with carfilzomib was 32 (1.1, 76.7) weeks in RRMM participants and 26 (1.0, 94.4) weeks in NDMM participants.
Change From Baseline in Hemoglobin Levels		Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15
Change From Baseline in Platelet Count		Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15
Change From Baseline in Neutrophil Count		Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15
Change From Baseline in Bilirubin		Baseline and Cycle 2 day 1
Change From Baseline in Creatinine		Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15

Measure	Description	Time Frame
Maximum Plasma Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group		Day 8 of Cycle 1 at predose, 15 minutes after the start of infusion, at the end of infusion, and 15 and 60 minutes after the end of infusion
Time to Maximum Plasma Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group

Name	Affiliation	Role
Amy Kimball, MD	Amgen	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Bakersfield	California	93309	United States
CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center

PubMed Identifier	Type	Citation	Retractions
31021005	Background	Biran N, Siegel D, Berdeja JG, Raje N, Cornell RF, Alsina M, Kovacsovics T, Fang B, Kimball AS, Landgren O. Weekly carfilzomib, lenalidomide, and dexamethasone in relapsed or refractory multiple myeloma: A phase 1b study. Am J Hematol. 2019 Jul;94(7):794-802. doi: 10.1002/ajh.25498. Epub 2019 May 13.

Label	URL
AmgenTrials clinical trials website	View source

ID	Title	Description
FG000	RRMM Dose-evaluation: Carfilzomib 56 mg/m²	Participants with relapsed or refractory multiple myeloma (RRMM) received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 56 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Dec 13, 2016	Oct 15, 2020

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With Adverse Events (AEs)

Safety and tolerability were evaluated according to the type, incidence, and severity of adverse events.

An AE is defined as any untoward medical occurrence in a clinical trial subject. The event does not necessarily have a causal relationship with study treatment.

A serious adverse event is defined as an AE that meets at least 1 of the following serious criteria:

fatal
life threatening
requires in-patient hospitalization or prolongation of existing hospitalization
results in persistent or significant disability/incapacity
congenital anomaly/birth defect
other medically important serious event

The severity of each AE was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03 where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death.

All participants who received at least 1 dose of study drug (safety analysis set).

Posted

Count of Participants

Participants

From the first dose of any study drug up to 30 days after the last dose of any study drug; median (range) duration of treatment with carfilzomib was 32 (1.1, 76.7) weeks in RRMM participants and 26 (1.0, 94.4) weeks in NDMM participants.

ID	Title	Description
OG000	RRMM Dose-evaluation: Carfilzomib 56 mg/m²	Participants with relapsed or refractory multiple myeloma (RRMM) received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 56 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.
OG001	RRMM Dose-evaluation: Carfilzomib 70 mg/m²	Participants with RRMM received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 70 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.
OG002	RRMM Dose-expansion: Carfilzomib 70 mg/m²	Participants with RRMM received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 70 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.
OG003	NDMM Dose-evaluation: Carfilzomib 56/70 mg/m²	Participants with newly diagnosed multiple myeloma (NDMM) received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1 day 1, 56 mg/m² on cycle 1 days 8 and 15, and then 70 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.

Units	Counts
Participants	OG00010 OG00112 OG00234 OG003

Title

Denominators

Categories

Any adverse event (AE)

Title	Measurements
	OG00010 OG00112 OG00234 OG003

Primary

Change From Baseline in Hemoglobin Levels

Participants in the safety analysis set with available data at Baseline and each time point.

Posted

Mean

Standard Deviation

g/L

Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15

ID	Title	Description
OG000	RRMM Dose-evaluation: Carfilzomib 56 mg/m²	Participants with relapsed or refractory multiple myeloma (RRMM) received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 56 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.
OG001	RRMM Dose-evaluation: Carfilzomib 70 mg/m²	Participants with RRMM received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 70 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.

Primary

Change From Baseline in Platelet Count

Participants in the safety analysis set with available data at Baseline and each time point.

Posted

Mean

Standard Deviation

10^9 cells/L

Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15

ID	Title	Description
OG000	RRMM Dose-evaluation: Carfilzomib 56 mg/m²	Participants with relapsed or refractory multiple myeloma (RRMM) received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 56 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.
OG001	RRMM Dose-evaluation: Carfilzomib 70 mg/m²	Participants with RRMM received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 70 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.

Primary

Change From Baseline in Neutrophil Count

Participants in the safety analysis set with available data at each time point.

Posted

Mean

Standard Deviation

10^9 cells/L

Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15

ID	Title	Description
OG000	RRMM Dose-evaluation: Carfilzomib 56 mg/m²	Participants with relapsed or refractory multiple myeloma (RRMM) received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 56 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.
OG001	RRMM Dose-evaluation: Carfilzomib 70 mg/m²	Participants with RRMM received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 70 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.

Primary

Change From Baseline in Bilirubin

Participants in the safety analysis set with available data at each time point.

Posted

Mean

Standard Deviation

µmol/L

Baseline and Cycle 2 day 1

ID	Title	Description
OG000	RRMM Dose-evaluation: Carfilzomib 56 mg/m²	Participants with relapsed or refractory multiple myeloma (RRMM) received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 56 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.
OG001	RRMM Dose-evaluation: Carfilzomib 70 mg/m²	Participants with RRMM received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 70 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.
OG002

Primary

Change From Baseline in Creatinine

Participants in the safety analysis set with available data at each time point.

Posted

Mean

Standard Deviation

µmol/L

Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15

ID	Title	Description
OG000	RRMM Dose-evaluation: Carfilzomib 56 mg/m²	Participants with relapsed or refractory multiple myeloma (RRMM) received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 56 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.
OG001	RRMM Dose-evaluation: Carfilzomib 70 mg/m²	Participants with RRMM received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 70 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.

Secondary

Maximum Plasma Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group

Participants who received at least 1 dose of study drug who had sufficient carfilzomib exposure and plasma concentration versus time data for the estimation of pharmacokinetic parameters by a non-compartmental analysis on day 8 of cycle 1.

Posted

Mean

Standard Deviation

ng/mL

Day 8 of Cycle 1 at predose, 15 minutes after the start of infusion, at the end of infusion, and 15 and 60 minutes after the end of infusion

ID	Title	Description
OG000	Carfilzomib 56 mg/m²	Participants who received carfilzomib 56 mg/m² on Cycle 1 day 8.
OG001	Carfilzomib 70 mg/m²	Participants who received carfilzomib 70 mg/m² on Cycle 1 day 8.

Units	Counts
Participants	OG000

Secondary

Time to Maximum Plasma Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group

Posted

Median

Full Range

hours

Day 8 of Cycle 1 at predose, 15 minutes after the start of infusion, at the end of infusion, and 15 and 60 minutes after the end of infusion

ID	Title	Description
OG000	Carfilzomib 56 mg/m²	Participants who received carfilzomib 56 mg/m² on Cycle 1 day 8.
OG001	Carfilzomib 70 mg/m²	Participants who received carfilzomib 70 mg/m² on Cycle 1 day 8.

Units	Counts
Participants	OG000

Secondary

Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group

Posted

Mean

Standard Deviation

hr*ng/mL

Day 8 of Cycle 1 at predose, 15 minutes after the start of infusion, at the end of infusion, and 15 and 60 minutes after the end of infusion

ID	Title	Description
OG000	Carfilzomib 56 mg/m²	Participants who received carfilzomib 56 mg/m² on Cycle 1 day 8.
OG001	Carfilzomib 70 mg/m²	Participants who received carfilzomib 70 mg/m² on Cycle 1 day 8.

Units	Counts
Participants	OG000

Secondary

Overall Response Rate (ORR)

Response was determined by the investigator based on the International Myeloma Working Group Uniform Response Criteria (IMWG URC). ORR was defined as the percentage of participants who achieved a best response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR). Responses must have been confirmed in 2 consecutive assessments at any time prior to initiation of any new therapy.

Disease assessments included serum protein electrophoresis (SPEP) with immunofixation, urine protein electrophoresis (UPEP; 24-hour assessment) with immunofixation, serum free light chain (SFLC), quantitative immunoglobulins, bone marrow aspirates to determine percent plasma cell involvement, and skeletal imaging for plasmacytoma evaluation.

All participants who received at least 1 dose of study drug

Posted

Number

95% Confidence Interval

percentage of participants

Response assessments were performed on day 1 of each treatment cycle from cycle 2 and then every 8 weeks during follow-up until disease progression. Median time on follow-up was 10.6 months in RRMM participants and 6.9 months in NDMM participants.

ID	Title	Description
OG000	RRMM Dose-evaluation: Carfilzomib 56 mg/m²	Participants with relapsed or refractory multiple myeloma (RRMM) received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 56 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.

Secondary

Complete Response Rate (CRR)

Complete Response Rate (CRR) is defined as the percentage of participants who achieved a best overall response of either stringent complete response (sCR) or complete response (CR) in accordance with International Myeloma Working Group-Uniform Response Criteria (IMWG-URC).

sCR: As for CR, and absence of clonal plasma cells in bone marrow (BM) CR: Negative serum and urine immunofixation, disappearance of any soft tissue plasmacytomas, < 5% plasma cells in BM, and normal SFLC ratio in participants with measurable disease only by SFLC.

Participants who received at least 1 dose of study drug.

Posted

Number

95% Confidence Interval

percentage of participants

ID	Title	Description
OG000	RRMM Dose-evaluation: Carfilzomib 56 mg/m²	Participants with relapsed or refractory multiple myeloma (RRMM) received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 56 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.
OG001

Secondary

Progression-free Survival (PFS)

PFS is defined as the time from the first day of study treatment to the earlier of disease progression or death due to any cause.

Disease progression was determined by the investigator according to IMWG-URC. Progressive Disease (PD): Increase of 25% from lowest value in serum M-component (absolute increase ≥ 0.5 g/dL), urine M-component (absolute increase ≥ 200 mg per 24 hours) and/or the difference between involved and uninvolved FLC levels (absolute increase >10 mg/dL) in patients without measurable serum and urine M-protein levels, and/or any new or increase in size of bone lesions or soft tissue plasmacytomas, or development of hypercalcemia.

PFS was analyzed using Kaplan-Meier methods. Participants who were alive with no documented PD, started new anticancer therapy before documentation of PD or death, had death or PD immediately after > 1 consecutively missed assessment visit, were lost to follow-up or withdrew consent were censored at the date of last disease assessment.

Participants who received at least 1 dose of study drug

Posted

Median

95% Confidence Interval

months

From first dose of study drug until the end of follow-up; Median time on follow-up was 10.6 months in RRMM participants and 6.9 months in NDMM participants.

ID	Title	Description
OG000	RRMM Dose-evaluation: Carfilzomib 56 mg/m²	Participants with relapsed or refractory multiple myeloma (RRMM) received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 56 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.

Secondary

Duration of Response (DOR)

Duration of response (DOR) was calculated for participants who achieved a confirmed PR or better based on Investigator assessment and according to the IMWG URC. Duration of overall response is defined as the time from first documentation of response to disease progression or death due to any cause. DOR was analyzed using Kaplan-Meier methods. Participants who were alive with no documented PD, started new anticancer therapy before documentation of PD or death, had death or PD immediately after > 1 consecutively missed disease assessment visit, were lost to follow-up, or withdrew consent were censored at the date of last disease assessment.

Participants who received at least 1 dose of study drug with an overall response of PR or better.

Posted

Median

95% Confidence Interval

months

From first dose of study drug until the end of follow-up; Median time on follow-up was 10.6 months in RRMM participants and 6.9 months in NDMM participants.

ID	Title	Description
OG000	RRMM Dose-evaluation: Carfilzomib 56 mg/m²	Participants with relapsed or refractory multiple myeloma (RRMM) received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 56 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG0030 affected9 at risk EG0040 affected9 at risk EG0051 affected33 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Thrombotic microangiopathy	Blood and lymphatic system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Angina pectoris	Cardiac disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Cardiac arrest	Cardiac disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0021 affected34 at risk EG003
Cardiac disorder	Cardiac disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0021 affected34 at risk EG003
Cardiac failure congestive	Cardiac disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Vitello-intestinal duct remnant	Congenital, familial and genetic disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Lower gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Asthenia	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Peripheral swelling	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Pyrexia	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Strangulated hernia	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Systemic inflammatory response syndrome	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Clostridium difficile colitis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Device related infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Orchitis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0021 affected34 at risk EG003
Pneumonia	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0023 affected34 at risk EG003
Pneumonia influenzal	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Pneumonia respiratory syncytial viral	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Sepsis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0021 affected34 at risk EG003
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0021 affected34 at risk EG003
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0021 affected34 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0021 affected34 at risk EG003
Pathological fracture	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0021 affected34 at risk EG003
Cerebrovascular accident	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0021 affected34 at risk EG003
Syncope	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0021 affected34 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Atelectasis	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0012 affected12 at risk EG0020 affected34 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0021 affected34 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk EG0021 affected34 at risk EG003
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Hypertension	Vascular disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 22.1	Systematic Assessment	EG0003 affected10 at risk EG0011 affected12 at risk EG0029 affected34 at risk EG0031 affected9 at risk EG0042 affected9 at risk EG0059 affected33 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Haemolysis	Blood and lymphatic system disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Haemolytic anaemia	Blood and lymphatic system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Iron deficiency anaemia	Blood and lymphatic system disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Leukopenia	Blood and lymphatic system disorders	MedDRA 22.1	Systematic Assessment	EG0003 affected10 at risk EG0010 affected12 at risk EG0021 affected34 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected10 at risk EG0013 affected12 at risk EG0024 affected34 at risk EG003
Pancytopenia	Blood and lymphatic system disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 22.1	Systematic Assessment	EG0005 affected10 at risk EG0014 affected12 at risk EG0026 affected34 at risk EG003
Thrombocytosis	Blood and lymphatic system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Acute coronary syndrome	Cardiac disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Cardiac failure congestive	Cardiac disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Palpitations	Cardiac disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0011 affected12 at risk EG0023 affected34 at risk EG003
Sinus tachycardia	Cardiac disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0021 affected34 at risk EG003
Tachycardia	Cardiac disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Ear congestion	Ear and labyrinth disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Ear haemorrhage	Ear and labyrinth disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Hypoacusis	Ear and labyrinth disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Tinnitus	Ear and labyrinth disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Cataract	Eye disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Dry eye	Eye disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0012 affected12 at risk EG0022 affected34 at risk EG003
Eye disorder	Eye disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Eye swelling	Eye disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Halo vision	Eye disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Vision blurred	Eye disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0012 affected12 at risk EG0024 affected34 at risk EG003
Visual impairment	Eye disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0021 affected34 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk EG0022 affected34 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0012 affected12 at risk EG0022 affected34 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0013 affected12 at risk EG0022 affected34 at risk EG003
Abdominal pain lower	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Chapped lips	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0003 affected10 at risk EG0017 affected12 at risk EG0027 affected34 at risk EG003
Dental caries	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0005 affected10 at risk EG0016 affected12 at risk EG00218 affected34 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0013 affected12 at risk EG0023 affected34 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Food poisoning	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0012 affected12 at risk EG0021 affected34 at risk EG003
Gingival pain	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Glossodynia	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Haematochezia	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Haemorrhoids	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Hypoaesthesia oral	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Lip dry	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Lip ulceration	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Mouth swelling	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0005 affected10 at risk EG0012 affected12 at risk EG00212 affected34 at risk EG003
Oral disorder	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Oral dysaesthesia	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk EG0021 affected34 at risk EG003
Palatal disorder	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0022 affected34 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0012 affected12 at risk EG0026 affected34 at risk EG003
Administration site oedema	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Asthenia	General disorders	MedDRA 22.1	Systematic Assessment	EG0003 affected10 at risk EG0012 affected12 at risk EG0020 affected34 at risk EG003
Chest discomfort	General disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0011 affected12 at risk EG0023 affected34 at risk EG003
Chest pain	General disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0011 affected12 at risk EG0024 affected34 at risk EG003
Chills	General disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0011 affected12 at risk EG0022 affected34 at risk EG003
Cyst	General disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Energy increased	General disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Fatigue	General disorders	MedDRA 22.1	Systematic Assessment	EG0005 affected10 at risk EG0014 affected12 at risk EG00221 affected34 at risk EG003
Gait disturbance	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0021 affected34 at risk EG003
Influenza like illness	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0023 affected34 at risk EG003
Injection site pain	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Localised oedema	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Malaise	General disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0011 affected12 at risk EG0021 affected34 at risk EG003
Mucosal inflammation	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0021 affected34 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Oedema	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0022 affected34 at risk EG003
Oedema peripheral	General disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0012 affected12 at risk EG0024 affected34 at risk EG003
Pain	General disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected10 at risk EG0011 affected12 at risk EG0021 affected34 at risk EG003
Peripheral swelling	General disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk EG0022 affected34 at risk EG003
Pyrexia	General disorders	MedDRA 22.1	Systematic Assessment	EG0005 affected10 at risk EG0012 affected12 at risk EG0025 affected34 at risk EG003
Swelling	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0022 affected34 at risk EG003
Swelling face	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Thirst	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Biliary dilatation	Hepatobiliary disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0021 affected34 at risk EG003
Hypogammaglobulinaemia	Immune system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Immune system disorder	Immune system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Seasonal allergy	Immune system disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk EG0021 affected34 at risk EG003
Bronchitis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0021 affected34 at risk EG003
Candida infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Cellulitis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0023 affected34 at risk EG003
Clostridium difficile infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Conjunctivitis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0021 affected34 at risk EG003
Cystitis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Ear infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk EG0021 affected34 at risk EG003
Fungal infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Fungal skin infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0021 affected34 at risk EG003
Gingivitis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Implant site abscess	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Influenza	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0022 affected34 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0012 affected12 at risk EG0021 affected34 at risk EG003
Oral candidiasis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0021 affected34 at risk EG003
Parainfluenzae virus infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0021 affected34 at risk EG003
Paronychia	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Pneumonia	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk EG0022 affected34 at risk EG003
Pneumonia respiratory syncytial viral	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Sinusitis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0002 affected10 at risk EG0011 affected12 at risk EG0024 affected34 at risk EG003
Skin infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0022 affected34 at risk EG003
Tinea infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk EG0021 affected34 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0003 affected10 at risk EG0017 affected12 at risk EG00214 affected34 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0023 affected34 at risk EG003
Vaginal infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA 22.1	Systematic Assessment	EG0002 affected10 at risk EG0011 affected12 at risk EG0024 affected34 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0011 affected12 at risk EG0023 affected34 at risk EG003
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Joint dislocation	Injury, poisoning and procedural complications	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Rib fracture	Injury, poisoning and procedural complications	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Skin laceration	Injury, poisoning and procedural complications	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0023 affected34 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0022 affected34 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0021 affected34 at risk EG003
Blood bilirubin increased	Investigations	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0012 affected12 at risk EG0025 affected34 at risk EG003
Blood creatinine increased	Investigations	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0011 affected12 at risk EG0024 affected34 at risk EG003
Blood uric acid decreased	Investigations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Blood urine present	Investigations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Brain natriuretic peptide increased	Investigations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0022 affected34 at risk EG003
Ejection fraction decreased	Investigations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0012 affected12 at risk EG0020 affected34 at risk EG003
Gamma-glutamyltransferase increased	Investigations	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Globulins increased	Investigations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Haemoglobin decreased	Investigations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0021 affected34 at risk EG003
Lymphocyte count decreased	Investigations	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk EG0022 affected34 at risk EG003
Neutrophil count decreased	Investigations	MedDRA 22.1	Systematic Assessment	EG0002 affected10 at risk EG0010 affected12 at risk EG0024 affected34 at risk EG003
Platelet count decreased	Investigations	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0013 affected12 at risk EG00211 affected34 at risk EG003
Weight decreased	Investigations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0022 affected34 at risk EG003
White blood cell count decreased	Investigations	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0011 affected12 at risk EG0025 affected34 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0013 affected12 at risk EG0024 affected34 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected10 at risk EG0012 affected12 at risk EG0023 affected34 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0025 affected34 at risk EG003
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk EG0022 affected34 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected10 at risk EG0012 affected12 at risk EG0028 affected34 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk EG0023 affected34 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0021 affected34 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0024 affected34 at risk EG003
Increased appetite	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Iron deficiency	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0024 affected34 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0028 affected34 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Joint swelling	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0022 affected34 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected10 at risk EG0016 affected12 at risk EG00210 affected34 at risk EG003
Muscle tightness	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0012 affected12 at risk EG0029 affected34 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0012 affected12 at risk EG0020 affected34 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0024 affected34 at risk EG003
Musculoskeletal stiffness	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0003 affected10 at risk EG0010 affected12 at risk EG0022 affected34 at risk EG003
Myalgia intercostal	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0022 affected34 at risk EG003
Osteolysis	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0021 affected34 at risk EG003
Osteonecrosis of jaw	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk EG0021 affected34 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected10 at risk EG0011 affected12 at risk EG0024 affected34 at risk EG003
Temporomandibular joint syndrome	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0022 affected34 at risk EG003
Neoplasm skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Ageusia	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Amnesia	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Burning sensation	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk EG0021 affected34 at risk EG003
Cognitive disorder	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0012 affected12 at risk EG0020 affected34 at risk EG003
Disturbance in attention	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Dizziness	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0005 affected10 at risk EG0013 affected12 at risk EG0027 affected34 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0013 affected12 at risk EG0020 affected34 at risk EG003
Headache	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0013 affected12 at risk EG0028 affected34 at risk EG003
Hyperaesthesia	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0021 affected34 at risk EG003
Hypoaesthesia	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0022 affected34 at risk EG003
Muscle spasticity	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0021 affected34 at risk EG003
Neuropathy peripheral	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0011 affected12 at risk EG0023 affected34 at risk EG003
Neurotoxicity	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0023 affected34 at risk EG003
Peripheral motor neuropathy	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0022 affected34 at risk EG003
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0012 affected12 at risk EG0023 affected34 at risk EG003
Restless legs syndrome	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Somnolence	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk EG0021 affected34 at risk EG003
Syncope	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Taste disorder	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Tremor	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected10 at risk EG0012 affected12 at risk EG0022 affected34 at risk EG003
Agitation	Psychiatric disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0021 affected34 at risk EG003
Confusional state	Psychiatric disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Depression	Psychiatric disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0022 affected34 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 22.1	Systematic Assessment	EG0004 affected10 at risk EG0013 affected12 at risk EG0027 affected34 at risk EG003
Irritability	Psychiatric disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0022 affected34 at risk EG003
Libido decreased	Psychiatric disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Mania	Psychiatric disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Mood altered	Psychiatric disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0023 affected34 at risk EG003
Restlessness	Psychiatric disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Anuria	Renal and urinary disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Chronic kidney disease	Renal and urinary disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0023 affected34 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0022 affected34 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Nephrolithiasis	Renal and urinary disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Nocturia	Renal and urinary disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0021 affected34 at risk EG003
Pollakiuria	Renal and urinary disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected10 at risk EG0012 affected12 at risk EG0022 affected34 at risk EG003
Urinary incontinence	Renal and urinary disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0003 affected10 at risk EG0015 affected12 at risk EG00211 affected34 at risk EG003
Dry throat	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0012 affected12 at risk EG0025 affected34 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0004 affected10 at risk EG0014 affected12 at risk EG0029 affected34 at risk EG003
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected10 at risk EG0013 affected12 at risk EG0022 affected34 at risk EG003
Dyspnoea paroxysmal nocturnal	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected10 at risk EG0012 affected12 at risk EG0023 affected34 at risk EG003
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0022 affected34 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected10 at risk EG0013 affected12 at risk EG0026 affected34 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0011 affected12 at risk EG0026 affected34 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0021 affected34 at risk EG003
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0021 affected34 at risk EG003
Pulmonary hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Respiratory tract congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk EG0021 affected34 at risk EG003
Sinus congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Upper-airway cough syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0022 affected34 at risk EG003
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0022 affected34 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0021 affected34 at risk EG003
Blister	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Cold sweat	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Dermatitis exfoliative generalised	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0012 affected12 at risk EG0020 affected34 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0012 affected12 at risk EG0022 affected34 at risk EG003
Night sweats	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0012 affected12 at risk EG0021 affected34 at risk EG003
Onychomadesis	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Petechiae	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0021 affected34 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected10 at risk EG0012 affected12 at risk EG0025 affected34 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0012 affected12 at risk EG0025 affected34 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0022 affected34 at risk EG003
Rash pruritic	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Skin lesion	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Skin mass	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0021 affected34 at risk EG003
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Deep vein thrombosis	Vascular disorders	MedDRA 22.1	Systematic Assessment	EG0003 affected10 at risk EG0010 affected12 at risk EG0022 affected34 at risk EG003
Femoral artery aneurysm	Vascular disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Flushing	Vascular disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0021 affected34 at risk EG003
Hypertension	Vascular disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0014 affected12 at risk EG0027 affected34 at risk EG003
Hypotension	Vascular disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected10 at risk EG0010 affected12 at risk EG0022 affected34 at risk EG003
Peripheral coldness	Vascular disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk EG0020 affected34 at risk EG003
Thrombophlebitis	Vascular disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Thrombophlebitis superficial	Vascular disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Vascular pain	Vascular disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003
Vein discolouration	Vascular disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected12 at risk EG0020 affected34 at risk EG003

ID	Title	Description
BG000	RRMM Dose-evaluation: Carfilzomib 56 mg/m²	Participants with relapsed or refractory multiple myeloma (RRMM) received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 56 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.
BG001	RRMM Dose-evaluation: Carfilzomib 70 mg/m²	Participants with RRMM received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 70 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.
BG002	RRMM Dose-expansion: Carfilzomib 70 mg/m²	Participants with RRMM received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 70 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.
BG003	NDMM Dose-evaluation: Carfilzomib 56/70 mg/m²	Participants with newly diagnosed multiple myeloma (NDMM) received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1 day 1, 56 mg/m² on cycle 1 days 8 and 15, and then 70 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.
BG004	NDMM Dose-expansion: Carfilzomib 70 mg/m²	Participants with NDMM received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 70 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.
BG005	NDMM Dose-expansion: Carfilzomib 56 mg/m²	Participants with NDMM received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 56 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.
BG006	Total	Total of all reporting groups

ID	Term
D054219	Neoplasms, Plasma Cell
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D020141	Hemostatic Disorders
D014652	Vascular Diseases
D002318	Cardiovascular Diseases
D010265	Paraproteinemias
D001796	Blood Protein Disorders
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D006474	Hemorrhagic Disorders
D008232	Lymphoproliferative Disorders
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases

ID	Term
D000074583	Short Chain Dehydrogenase-Reductases
D064430	NAD (+) and NADP (+) Dependent Alcohol Oxidoreductases
D000429	Alcohol Oxidoreductases
D010088	Oxidoreductases
D004798	Enzymes
D045762	Enzymes and Coenzymes
D025521	Tumor Suppressor Proteins
D009363	Neoplasm Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D010797	Phthalimides
D010795	Phthalic Acids
D000146	Acids, Carbocyclic
D002264	Carboxylic Acids
D009930	Organic Chemicals
D010881	Piperidones
D010880	Piperidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D054833	Isoindoles
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D011246	Pregnadienetriols
D011245	Pregnadienes
D011278	Pregnanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds
D013259	Steroids, Fluorinated

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	RRMM Dose-evaluation: Carfilzomib 56 mg/m²	Participants with relapsed or refractory multiple myeloma (RRMM) received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 56 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.	0	10	4	10	10	10
EG001	RRMM Dose-evaluation: Carfilzomib 70 mg/m²	Participants with RRMM received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 70 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.	0	12	5	12	12	12
EG002	RRMM Dose-expansion: Carfilzomib 70 mg/m²	Participants with RRMM received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 70 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.	2	34	10	34	33	34
EG003	NDMM Dose-evaluation: Carfilzomib 56/70 mg/m²	Participants with newly diagnosed multiple myeloma (NDMM) received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1 day 1, 56 mg/m² on cycle 1 days 8 and 15, and then 70 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.	0	9	3	9	9	9
EG004	NDMM Dose-expansion: Carfilzomib 70 mg/m²	Participants with NDMM received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 70 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.	0	9	3	9	9	9
EG005	NDMM Dose-expansion: Carfilzomib 56 mg/m²	Participants with NDMM received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 56 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.	0	33	11	33	33	33

ID	Term
C524865	carfilzomib
D000074584	WW Domain-Containing Oxidoreductase
D000077269	Lenalidomide
D003907	Dexamethasone