NCT02312258 · OUTCOME
Correlation Between Frailty Status and PFS and OS
A Study of Oral Ixazomib Maintenance Therapy in Participants With Newly Diagnosed Multiple Myeloma (NDMM) Not Treated With Stem Cell Transplantation (SCT) · Source last updated 2023-09-21
Results reported by the registry submitting party. Population, time horizon, units and missing values must be read together.
- Measure
- MEDIAN
- Unit
- months
- Interval / dispersion
- 95% Confidence Interval
- Time frame
- From randomization up to 52 months
What was measured
Participant's frailty status is classified as fit, unfit or frail on the bases of 4 components: age, the Charlson comorbidity scoring system without age weighting, the Katz index of independence in activities of daily living, and the Lawton instrumental activities of daily living scale. The sum of the 4 frailty scores equals the total frailty score. A total frailty score of 0 corresponds to a frailty status of fit; a total score of 1, to unfit; and a total score of 2 or more, to frail. PFS is defined as the time from the date of randomization to the date of first documentation of PD or death from any cause, as evaluated by an IRC according to IMWG criteria, or death due to any cause, whichever occurs first, assessed for up to 52 months in this outcome measure. OS will be measured as the time from the date of randomization to the date of death, assessed for up to 52 months in this outcome measure.
Analysis population: ITT Population included all participants who were randomized and had post-randomization data. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analysis for the specified category.
Groups in this outcome
Placebo
Ixazomib 3 mg, capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 through 26.
Ixazomib
Ixazomib 3 mg, capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 to 4 that may have been escalated to 4 mg thereafter up to Cycle 26.
Group identifiers and denominators belong to this outcome only. They may differ in another outcome or in safety reporting.
Analysis denominator · Participants
| Group | Source count |
|---|
| Placebo | 112 |
|---|
| Ixazomib | 172 |
|---|
Reported measurements
PFS Based on Frailty Status of Fit
Analysis denominator · Participants
| Group | Source count |
|---|
| Placebo | 112 |
|---|
| Ixazomib | 172 |
|---|
Values in months · Interval/dispersion: 95% Confidence Interval| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Placebo | 8.5 | Not reported | 7.39 | 10.41 | Not reported |
|---|
| Ixazomib | 18.6 | Not reported | 12.75 | 25.63 | Not reported |
|---|
PFS Based on Frailty Status of Unfit
Analysis denominator · Participants
| Group | Source count |
|---|
| Placebo | 98 |
|---|
| Ixazomib | 147 |
|---|
Values in months · Interval/dispersion: 95% Confidence Interval| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Placebo | 10.6 | Not reported | 7.39 | 14.23 | Not reported |
|---|
| Ixazomib | 17.6 | Not reported | 13.17 | 21.78 | Not reported |
|---|
PFS Based on Frailty Status of Frail
Analysis denominator · Participants
| Group | Source count |
|---|
| Placebo | 68 |
|---|
| Ixazomib | 102 |
|---|
Values in months · Interval/dispersion: 95% Confidence Interval| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Placebo | 11.1 | Not reported | 8.44 | 15.67 | Not reported |
|---|
| Ixazomib | 15.4 | Not reported | 11.10 | 23.75 | Not reported |
|---|
OS Based on Frailty Status of Fit
Analysis denominator · Participants
| Group | Source count |
|---|
| Placebo | 112 |
|---|
| Ixazomib | 172 |
|---|
Values in months · Interval/dispersion: 95% Confidence Interval| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Placebo | NA | Not reported | NA | NA | Median, upper, and lower limit of CI were not estimable due to censoring. |
|---|
| Ixazomib | NA | Not reported | NA | NA | Median, upper, and lower limit of CI were not estimable due to censoring. |
|---|
OS Based on Frailty Status of Unfit
Analysis denominator · Participants
| Group | Source count |
|---|
| Placebo | 98 |
|---|
| Ixazomib | 147 |
|---|
Values in months · Interval/dispersion: 95% Confidence Interval| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Placebo | NA | Not reported | NA | NA | Median, upper, and lower limit of CI were not estimable due to censoring. |
|---|
| Ixazomib | NA | Not reported | 39.59 | NA | Median and lower limit of CI were not estimable due to censoring. |
|---|
OS Based on Frailty Status of Frail
Analysis denominator · Participants
| Group | Source count |
|---|
| Placebo | 68 |
|---|
| Ixazomib | 102 |
|---|
Values in months · Interval/dispersion: 95% Confidence Interval| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Placebo | 42.5 | Not reported | 29.93 | NA | Upper limit of CI was not estimable due to censoring. |
|---|
| Ixazomib | 46.5 | Not reported | 34.30 | 46.52 | Not reported |
|---|
Source statistical analyses
Group order, estimate direction, methods and comments are retained. No treatment ranking is inferred.
- ci Lower Limit
- 0.387
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 95
- ci Upper Limit
- 0.727
- group Description
- PFS Based on Frailty Status of Fit
- non Inferiority Type
- SUPERIORITY
- other Analysis Description
- P-value comparing PFS between treatment groups was based on Log-rank test stratified by initial therapy (proteasome inhibitor-containing or not), ISS stage before initial therapy (stage I or II vs stage III), and age (\<75 vs \>=75 years) at randomization.
Hazard ratio was based on an unadjusted Cox's proportional hazard regression model stratified by initial therapy (proteasome inhibitor-containing or not), ISS stage before initial therapy (stage I or II vs stage III), and age (\<75 vs \>=75 years) at randomization, comparing the hazard rate of ixazomib arm over the hazard rate of placebo arm. A less than 1 hazard ratio was to be considered statistically significant.
- p Value
- <0.001
- param Type
- Hazard Ratio (HR)
- param Value
- 0.530
- statistical Method
- Log Rank
- ci Lower Limit
- 0.526
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 95
- ci Upper Limit
- 1.058
- group Description
- PFS Based on Frailty Status of Unfit
- non Inferiority Type
- SUPERIORITY
- other Analysis Description
- P-value comparing PFS between treatment groups was based on Log-rank test stratified by initial therapy (proteasome inhibitor-containing or not), ISS stage before initial therapy (stage I or II vs stage III), and age (\<75 vs \>=75 years) at randomization.
Hazard ratio was based on an unadjusted Cox's proportional hazard regression model stratified by initial therapy (proteasome inhibitor-containing or not), ISS stage before initial therapy (stage I or II vs stage III), and age (\<75 vs \>=75 years) at randomization, comparing the hazard rate of ixazomib arm over the hazard rate of placebo arm. A less than 1 hazard ratio was to be considered statistically significant.
- p Value
- =0.098
- param Type
- Hazard Ratio (HR)
- param Value
- 0.746
- statistical Method
- Log Rank
- ci Lower Limit
- 0.481
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 95
- ci Upper Limit
- 1.117
- group Description
- PFS Based on Frailty Status of Frail
- non Inferiority Type
- SUPERIORITY
- other Analysis Description
- P-value comparing PFS between treatment groups was based on Log-rank test stratified by initial therapy (proteasome inhibitor-containing or not), ISS stage before initial therapy (stage I or II vs stage III), and age (\<75 vs \>=75 years) at randomization.
Hazard ratio was based on an unadjusted Cox's proportional hazard regression model stratified by initial therapy (proteasome inhibitor-containing or not), ISS stage before initial therapy (stage I or II vs stage III), and age (\<75 vs \>=75 years) at randomization, comparing the hazard rate of ixazomib arm over the hazard rate of placebo arm. A less than 1 hazard ratio was to be considered statistically significant.
- p Value
- =0.147
- param Type
- Hazard Ratio (HR)
- param Value
- 0.733
- statistical Method
- Log Rank
- ci Lower Limit
- 0.502
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 95
- ci Upper Limit
- 1.602
- group Description
- OS Based on Frailty Status of Fit
- non Inferiority Type
- SUPERIORITY
- other Analysis Description
- P-value comparing OS between treatment groups was based on log-rank test stratified by initial therapy (proteasome inhibitor-containing or not), ISS stage before initial therapy (stage I or II vs stage III), age (\<75 vs \>=75 years) at randomization, and best response to initial therapy (CR or VGPR vs PR).
Hazard ratio was based on an unadjusted Cox's proportional hazard regression model stratified by initial therapy (proteasome inhibitor-containing or not), ISS stage before initial therapy (stage I or II vs stage III), age (\<75 vs \>=75 years) at randomization, and best response to initial therapy (CR or VGPR vs PR), comparing the hazard rate of ixazomib arm over the hazard rate of placebo arm. A less than 1 hazard ratio was to be considered statistically significant.
- p Value
- =0.714
- param Type
- Hazard Ratio (HR)
- param Value
- 0.897
- statistical Method
- Log Rank
- ci Lower Limit
- 0.850
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 95
- ci Upper Limit
- 3.601
- group Description
- OS Based on Frailty Status of Unfit
- non Inferiority Type
- SUPERIORITY
- other Analysis Description
- P-value comparing OS between treatment groups was based on log-rank test stratified by initial therapy (proteasome inhibitor-containing or not), ISS stage before initial therapy (stage I or II vs stage III), age (\<75 vs \>=75 years) at randomization, and best response to initial therapy (CR or VGPR vs PR).
Hazard ratio was based on an unadjusted Cox's proportional hazard regression model stratified by initial therapy (proteasome inhibitor-containing or not), ISS stage before initial therapy (stage I or II vs stage III), age (\<75 vs \>=75 years) at randomization, and best response to initial therapy (CR or VGPR vs PR), comparing the hazard rate of ixazomib arm over the hazard rate of placebo arm. A less than 1 hazard ratio was to be considered statistically significant.
- p Value
- =0.124
- param Type
- Hazard Ratio (HR)
- param Value
- 1.750
- statistical Method
- Log Rank
- ci Lower Limit
- 0.448
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 95
- ci Upper Limit
- 1.627
- group Description
- OS Based on Frailty Status of Frail
- non Inferiority Type
- SUPERIORITY
- other Analysis Description
- P-value comparing OS between treatment groups was based on log-rank test stratified by initial therapy (proteasome inhibitor-containing or not), ISS stage before initial therapy (stage I or II vs stage III), age (\<75 vs \>=75 years) at randomization, and best response to initial therapy (CR or VGPR vs PR).
Hazard ratio was based on an unadjusted Cox's proportional hazard regression model stratified by initial therapy (proteasome inhibitor-containing or not), ISS stage before initial therapy (stage I or II vs stage III), age (\<75 vs \>=75 years) at randomization, and best response to initial therapy (CR or VGPR vs PR), comparing the hazard rate of ixazomib arm over the hazard rate of placebo arm. A less than 1 hazard ratio was to be considered statistically significant.
- p Value
- =0.630
- param Type
- Hazard Ratio (HR)
- param Value
- 0.854
- statistical Method
- Log Rank
Complete source fields
- analyses
- ci Lower Limit
- 0.387
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 95
- ci Upper Limit
- 0.727
- group Description
- PFS Based on Frailty Status of Fit
- non Inferiority Type
- SUPERIORITY
- other Analysis Description
- P-value comparing PFS between treatment groups was based on Log-rank test stratified by initial therapy (proteasome inhibitor-containing or not), ISS stage before initial therapy (stage I or II vs stage III), and age (\<75 vs \>=75 years) at randomization.
Hazard ratio was based on an unadjusted Cox's proportional hazard regression model stratified by initial therapy (proteasome inhibitor-containing or not), ISS stage before initial therapy (stage I or II vs stage III), and age (\<75 vs \>=75 years) at randomization, comparing the hazard rate of ixazomib arm over the hazard rate of placebo arm. A less than 1 hazard ratio was to be considered statistically significant.
- p Value
- <0.001
- param Type
- Hazard Ratio (HR)
- param Value
- 0.530
- statistical Method
- Log Rank
- ci Lower Limit
- 0.526
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 95
- ci Upper Limit
- 1.058
- group Description
- PFS Based on Frailty Status of Unfit
- non Inferiority Type
- SUPERIORITY
- other Analysis Description
- P-value comparing PFS between treatment groups was based on Log-rank test stratified by initial therapy (proteasome inhibitor-containing or not), ISS stage before initial therapy (stage I or II vs stage III), and age (\<75 vs \>=75 years) at randomization.
Hazard ratio was based on an unadjusted Cox's proportional hazard regression model stratified by initial therapy (proteasome inhibitor-containing or not), ISS stage before initial therapy (stage I or II vs stage III), and age (\<75 vs \>=75 years) at randomization, comparing the hazard rate of ixazomib arm over the hazard rate of placebo arm. A less than 1 hazard ratio was to be considered statistically significant.
- p Value
- =0.098
- param Type
- Hazard Ratio (HR)
- param Value
- 0.746
- statistical Method
- Log Rank
- ci Lower Limit
- 0.481
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 95
- ci Upper Limit
- 1.117
- group Description
- PFS Based on Frailty Status of Frail
- non Inferiority Type
- SUPERIORITY
- other Analysis Description
- P-value comparing PFS between treatment groups was based on Log-rank test stratified by initial therapy (proteasome inhibitor-containing or not), ISS stage before initial therapy (stage I or II vs stage III), and age (\<75 vs \>=75 years) at randomization.
Hazard ratio was based on an unadjusted Cox's proportional hazard regression model stratified by initial therapy (proteasome inhibitor-containing or not), ISS stage before initial therapy (stage I or II vs stage III), and age (\<75 vs \>=75 years) at randomization, comparing the hazard rate of ixazomib arm over the hazard rate of placebo arm. A less than 1 hazard ratio was to be considered statistically significant.
- p Value
- =0.147
- param Type
- Hazard Ratio (HR)
- param Value
- 0.733
- statistical Method
- Log Rank
- ci Lower Limit
- 0.502
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 95
- ci Upper Limit
- 1.602
- group Description
- OS Based on Frailty Status of Fit
- non Inferiority Type
- SUPERIORITY
- other Analysis Description
- P-value comparing OS between treatment groups was based on log-rank test stratified by initial therapy (proteasome inhibitor-containing or not), ISS stage before initial therapy (stage I or II vs stage III), age (\<75 vs \>=75 years) at randomization, and best response to initial therapy (CR or VGPR vs PR).
Hazard ratio was based on an unadjusted Cox's proportional hazard regression model stratified by initial therapy (proteasome inhibitor-containing or not), ISS stage before initial therapy (stage I or II vs stage III), age (\<75 vs \>=75 years) at randomization, and best response to initial therapy (CR or VGPR vs PR), comparing the hazard rate of ixazomib arm over the hazard rate of placebo arm. A less than 1 hazard ratio was to be considered statistically significant.
- p Value
- =0.714
- param Type
- Hazard Ratio (HR)
- param Value
- 0.897
- statistical Method
- Log Rank
- ci Lower Limit
- 0.850
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 95
- ci Upper Limit
- 3.601
- group Description
- OS Based on Frailty Status of Unfit
- non Inferiority Type
- SUPERIORITY
- other Analysis Description
- P-value comparing OS between treatment groups was based on log-rank test stratified by initial therapy (proteasome inhibitor-containing or not), ISS stage before initial therapy (stage I or II vs stage III), age (\<75 vs \>=75 years) at randomization, and best response to initial therapy (CR or VGPR vs PR).
Hazard ratio was based on an unadjusted Cox's proportional hazard regression model stratified by initial therapy (proteasome inhibitor-containing or not), ISS stage before initial therapy (stage I or II vs stage III), age (\<75 vs \>=75 years) at randomization, and best response to initial therapy (CR or VGPR vs PR), comparing the hazard rate of ixazomib arm over the hazard rate of placebo arm. A less than 1 hazard ratio was to be considered statistically significant.
- p Value
- =0.124
- param Type
- Hazard Ratio (HR)
- param Value
- 1.750
- statistical Method
- Log Rank
- ci Lower Limit
- 0.448
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 95
- ci Upper Limit
- 1.627
- group Description
- OS Based on Frailty Status of Frail
- non Inferiority Type
- SUPERIORITY
- other Analysis Description
- P-value comparing OS between treatment groups was based on log-rank test stratified by initial therapy (proteasome inhibitor-containing or not), ISS stage before initial therapy (stage I or II vs stage III), age (\<75 vs \>=75 years) at randomization, and best response to initial therapy (CR or VGPR vs PR).
Hazard ratio was based on an unadjusted Cox's proportional hazard regression model stratified by initial therapy (proteasome inhibitor-containing or not), ISS stage before initial therapy (stage I or II vs stage III), age (\<75 vs \>=75 years) at randomization, and best response to initial therapy (CR or VGPR vs PR), comparing the hazard rate of ixazomib arm over the hazard rate of placebo arm. A less than 1 hazard ratio was to be considered statistically significant.
- p Value
- =0.630
- param Type
- Hazard Ratio (HR)
- param Value
- 0.854
- statistical Method
- Log Rank
- classes
- categories
- measurements
- group Id
- OG000
- lower Limit
- 7.39
- upper Limit
- 10.41
- value
- 8.5
- group Id
- OG001
- lower Limit
- 12.75
- upper Limit
- 25.63
- value
- 18.6
- denoms
- counts
- group Id
- OG000
- value
- 112
- group Id
- OG001
- value
- 172
- units
- Participants
- title
- PFS Based on Frailty Status of Fit
- categories
- measurements
- group Id
- OG000
- lower Limit
- 7.39
- upper Limit
- 14.23
- value
- 10.6
- group Id
- OG001
- lower Limit
- 13.17
- upper Limit
- 21.78
- value
- 17.6
- denoms
- counts
- group Id
- OG000
- value
- 98
- group Id
- OG001
- value
- 147
- units
- Participants
- title
- PFS Based on Frailty Status of Unfit
- categories
- measurements
- group Id
- OG000
- lower Limit
- 8.44
- upper Limit
- 15.67
- value
- 11.1
- group Id
- OG001
- lower Limit
- 11.10
- upper Limit
- 23.75
- value
- 15.4
- denoms
- counts
- group Id
- OG000
- value
- 68
- group Id
- OG001
- value
- 102
- units
- Participants
- title
- PFS Based on Frailty Status of Frail
- categories
- measurements
- comment
- Median, upper, and lower limit of CI were not estimable due to censoring.
- group Id
- OG000
- lower Limit
- NA
- upper Limit
- NA
- value
- NA
- comment
- Median, upper, and lower limit of CI were not estimable due to censoring.
- group Id
- OG001
- lower Limit
- NA
- upper Limit
- NA
- value
- NA
- denoms
- counts
- group Id
- OG000
- value
- 112
- group Id
- OG001
- value
- 172
- units
- Participants
- title
- OS Based on Frailty Status of Fit
- categories
- measurements
- comment
- Median, upper, and lower limit of CI were not estimable due to censoring.
- group Id
- OG000
- lower Limit
- NA
- upper Limit
- NA
- value
- NA
- comment
- Median and lower limit of CI were not estimable due to censoring.
- group Id
- OG001
- lower Limit
- 39.59
- upper Limit
- NA
- value
- NA
- denoms
- counts
- group Id
- OG000
- value
- 98
- group Id
- OG001
- value
- 147
- units
- Participants
- title
- OS Based on Frailty Status of Unfit
- categories
- measurements
- comment
- Upper limit of CI was not estimable due to censoring.
- group Id
- OG000
- lower Limit
- 29.93
- upper Limit
- NA
- value
- 42.5
- group Id
- OG001
- lower Limit
- 34.30
- upper Limit
- 46.52
- value
- 46.5
- denoms
- counts
- group Id
- OG000
- value
- 68
- group Id
- OG001
- value
- 102
- units
- Participants
- title
- OS Based on Frailty Status of Frail
- denoms
- counts
- group Id
- OG000
- value
- 112
- group Id
- OG001
- value
- 172
- units
- Participants
- description
- Participant's frailty status is classified as fit, unfit or frail on the bases of 4 components: age, the Charlson comorbidity scoring system without age weighting, the Katz index of independence in activities of daily living, and the Lawton instrumental activities of daily living scale. The sum of the 4 frailty scores equals the total frailty score. A total frailty score of 0 corresponds to a frailty status of fit; a total score of 1, to unfit; and a total score of 2 or more, to frail. PFS is defined as the time from the date of randomization to the date of first documentation of PD or death from any cause, as evaluated by an IRC according to IMWG criteria, or death due to any cause, whichever occurs first, assessed for up to 52 months in this outcome measure. OS will be measured as the time from the date of randomization to the date of death, assessed for up to 52 months in this outcome measure.
- dispersion Type
- 95% Confidence Interval
- groups
- description
- Ixazomib 3 mg, capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 through 26.
- id
- OG000
- title
- Placebo
- description
- Ixazomib 3 mg, capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 to 4 that may have been escalated to 4 mg thereafter up to Cycle 26.
- id
- OG001
- title
- Ixazomib
- param Type
- MEDIAN
- population Description
- ITT Population included all participants who were randomized and had post-randomization data. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analysis for the specified category.
- reporting Status
- POSTED
- time Frame
- From randomization up to 52 months
- title
- Correlation Between Frailty Status and PFS and OS
- type
- SECONDARY
- unit Of Measure
- months
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Preserved source evidence · Not medical advice
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