Multiple Myeloma
Conditions
Keywords
Myeloma, Multiple Myeloma, relapsed Multiple Myeloma, refractory Multiple Myeloma, PF-06863135, BCMA, bispecific, bispecific antibody, BCMA-CD3 bispecific, Elranatamab, MagnetisMM-3
Brief summary
This study is to understand how well elranatamab (PF-06863135) may be used for relapsed refractory multiple myeloma (RRMM). Sometimes MM might improve at first, but then gets resistant to the treatment and starts growing again (known as relapsed refractory). This study medicine will be compared with standard-of-care (SOC) therapies used in real-world clinical practice. For people receiving elranatamab, the investigators will use data from the phase 2 clinical trial (MagnetisMM-3). The investigators will also use data from multiple real-world sources, representing the SOC in clinical practice. This study does not seek any participants for enrollment. The investigators will compare the experiences of people receiving elranatamab to people receiving SOC therapies. This way, it will help the investigators to know how well elranatamab can be used for RRMM treatment.
Interventions
DRUGElranatamab
BCMA-CD3 bispecific antibody
DRUGStandard of care
Standard of care
Sponsors
Pfizer
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Weeks to No maximum
Healthy volunteers
No
Inclusion criteria
* Aged 18 years and older at index date * Diagnosis of MM * Measurable disease according to IMWG criteria * ECOG performance status ≤2 * Refractory to at least 1 proteasome inhibitor, 1 immunomodulatory drug, and 1 anti-CD38 treatment (ie, triple-class refractory \[TCR\]) * At least 1 treatment following their TCR eligibility
Exclusion criteria
* Acute plasma cell leukemia * Amyloidosis * Smoldering MM * Stem cell transplant within 12 weeks of index or active graft versus host disease (GVHD) * Active malignancy within 3 years before index, except for basal cell or squamous cell skin cancer or carcinoma in situ * Administration with an investigational drug within 30 days prior to index
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PFS: Study C1071003 Cohort A Versus Flatiron Cohort - Using IPTW Analysis | C1071003:First dose to confirmed PD/death due to any cause or censoring whichever occurred first(maximum of 15 months);Flatiron:Initiation of first line post TCR MM to PD/death due to any cause or censoring,whichever occurred first(maximum of 66.9 months) | PFS: a) C1071003 Cohort A, PFS: time from the date of the first dose until confirmed PD per IMWG criteria or death due to any cause, whichever occurred first. B) Flatiron Health: time from initiation of the first line after participant identified as having TCR MM to either the date of progression or death due to any cause, whichever occurred first. IMWG criteria for progression: an increase of \>= 25% from baseline/nadir value in any one or more of the following: an absolute increase in serum M-protein by SPEP by \>= 0.5 g/dL; serum M-protein \>= 1 g/dL if the lowest M component was \>= 5 g/dL; an absolute increase in urine M-protein by UPEP by \>=200 mg/24 h; in participants without measurable serum and urine M-protein levels, an absolute increase in the difference between involved and uninvolved FLC levels of \>10 mg/dL. Retrospective data was retrieved and observed in the current study for approximately 1.5 months. Kaplan Meier Method was used for analysis. |
| Progression Free Survival (PFS): Study C1071003 Cohort A Versus RWD COTA Cohort- Using Unweighted Analysis | C1071003:First dose to confirmed PD/ death due to any cause or censoring whichever occurred first (maximum of 15 months);COTA:Initiation of first line post TCR MM to PD/ death due to any cause or censoring whichever occurred first (maximum of 64.3 months) | PFS: a) C1071003 Cohort A: time from the date of the first dose until confirmed progressive disease (PD) per IMWG criteria or death due to any cause, whichever occurred first; b) RWD COTA: time from initiation of the first line after participant identified as having TCR MM to either the date of progression or death due to any cause, whichever occurred first. IMWG criteria for progression: an increase of \>=25% (Percent) from the lowest response value in any 1 or more of the criteria: serum protein electrophoresis (SPEP) with an absolute increase \>0.5 gram/deciliter (g/dL); 24-hour(h) urine protein electrophoresis (UPEP) with an absolute increase \>200 microgram (mg)/24 h; in participants without measurable serum and urine M-protein, the absolute increase of \>10 mg/dL in the difference between involved and uninvolved free light chain (FLC) levels; or an absolute bone marrow plasma cell \>10%. Retrospective data was retrieved and observed in the current study for approximately 1.5 months. |
| PFS: C1071003 Cohort A Versus COTA Cohort- Using Inverse Probability of Treatment Weights (IPTW) | C1071003:First dose to confirmed PD/ death due to any cause or censoring whichever occurred first (maximum of 15 months);COTA:Initiation of first line post TCR MM to PD/ death due to any cause or censoring whichever occurred first (maximum of 64.3 months) | PFS: a) C1071003 Cohort A: time from the date of the first dose until confirmed PD per IMWG criteria or death due to any cause, whichever occurred first; b) COTA: time from initiation of the first line after participant identified as having TCR MM to either the date of progression or death due to any cause, whichever occurred first. IMWG criteria for progression: an increase of \>=25% from the lowest response value in any 1 or more of the criteria: SPEP with an absolute increase \>0.5 g/dL; 24-hour UPEP with an absolute increase \>200 mg/24 h; in participants without measurable serum and urine M-protein, the absolute increase of \>10 mg/dL in the difference between involved and uninvolved FLC levels; or an absolute bone marrow plasma cell percentage \>10%. Retrospective data was retrieved and observed in the current study for approximately 1.5 months. Participants without an event were censored at date of last adequate disease assessment or the data cut-off. Kaplan Meier method was used. |
| PFS: Study C1071003 Cohort A Versus Flatiron Cohort - Using Unweighted Analysis | C1071003:First dose to confirmed PD/death due to any cause or censoring whichever occurred first(maximum of 15 months);Flatiron:Initiation of first line post TCR MM to PD/death due to any cause or censoring,whichever occurred first(maximum of 66.9 months) | PFS: a) C1071003 Cohort A, PFS: time from the date of the first dose until confirmed PD per IMWG criteria or death due to any cause, whichever occurred first. B) Flatiron Health: time from initiation of the first line after participant identified as having TCR MM to either the date of progression or death due to any cause, whichever occurred first. IMWG criteria for progression: an increase of \>= 25% from baseline/nadir value in any one or more of the following: an absolute increase in serum M-protein by SPEP by \>= 0.5 g/dL; serum M-protein \>= 1 g/dL if the lowest M component was \>= 5 g/dL; an absolute increase in urine M-protein by UPEP by \>=200 mg/24 h; in participants without measurable serum and urine M-protein levels, an absolute increase in the difference between involved and uninvolved FLC levels of \>10 mg/dL. Retrospective data was retrieved and observed in the current study for approximately 1.5 months. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS): Study C1071003 Cohort A Versus RWD COTA Cohort- Using Unweighted Analysis | C1071003: The date of the first dose until death due to any cause or censoring (maximum up to 15 months); COTA: First line after participant identified as having TCR MM until the date of death due to any cause or censoring (maximum of 64.3 months) | OS: a) C1071003 Cohort A: OS was defined as time from the date of the first dose until death due to any cause; b) COTA Cohort: OS was defined as time from initiation of the first line after participant identified as having TCR MM until the date of death due to any cause. Kaplan Meier Method was used for analysis. Participants without an event were censored at the latest available record or the data cut-off. |
| OS: Study C1071003 Cohort A Versus RWD COTA Cohort- Using IPTW Analysis | C1071003: The date of the first dose until death due to any cause or censoring (maximum up to 15 months); COTA: First line after participant identified as having TCR MM until the date of death due to any cause or censoring (maximum of 64.3 months) | OS: a) C1071003 Cohort A: OS was defined as time from the date of the first dose until death due to any cause; b) COTA Cohort: OS was defined as time from initiation of the first line after participant identified as having TCR MM until the date of death due to any cause. Kaplan Meier Method was used for analysis. Participants without an event were censored at the latest available record or the data cut-off. |
| OS: Study C1071003 Cohort A Versus Flatiron Cohort - Using Unweighted Analysis | C1071003: The date of the first dose until death due to any cause or censoring (maximum up to 15 months); Flatiron: First line after participant identified as having TCR MM until the date of death due to any cause or censoring (maximum of 66.9 months) | OS: a) C1071003 Cohort A: OS was defined as time from the date of the first dose until death due to any cause; B) Flatiron Cohort: OS was defined as time from initiation of the first line after participant identified as having TCR MM until the date of death due to any cause. Kaplan Meier Method was used for analysis. Participants without an event were censored at the latest available record or the data cut-off. |
| OS: Study C1071003 Cohort A Versus Flatiron Cohort - Using IPTW Analysis | C1071003: The date of the first dose until death due to any cause or censoring (maximum up to 15 months); Flatiron: First line after participant identified as having TCR MM until the date of death due to any cause or censoring (maximum of 66.9 months) | OS: a) C1071003 Cohort A: OS was defined as time from the date of the first dose until death due to any cause; B) Flatiron Cohort: OS was defined as time from initiation of the first line after participant identified as having TCR MM until the date of death due to any cause. Kaplan Meier Method was used for analysis. Participants without an event were censored at the latest available record or the data cut-off. |
Countries
United States
Participant flow
Recruitment details
This retrospective cohort study used participant level data from study C1071003 (NCT04649359), and external control arms identified from real world data (RWD) sources.
Participants by arm
| Arm | Count |
|---|---|
| C1071003 Cohort A Eligible participants with TCR MM, who were BCMA naïve, who were enrolled between 2 February 2021 to 07 January 2022 and who were treated with elranatamab in study C1071003 were included. | 123 |
| RWD: COTA Eligible participants with TCR MM who were treated with SOC therapies in real world clinical practice setting, identified from COTA database were included. This arm served as external control arm. | 239 |
| RWD: Flatiron Health Eligible participants with TCR MM who were treated with SOC therapies in real world clinical practice setting, identified from Flatiron Health database were included. This arm served as external control arm. | 152 |
| Total | 514 |
Baseline characteristics
| Characteristic | C1071003 Cohort A | RWD: COTA | RWD: Flatiron Health | Total |
|---|---|---|---|---|
| Age, Continuous | 67.1 Years STANDARD_DEVIATION 9.4 | 68.0 Years STANDARD_DEVIATION 9.4 | 69.5 Years STANDARD_DEVIATION 10 | 68.2 Years STANDARD_DEVIATION 9.6 |
| Race/Ethnicity, Customized Non-white | 51 Participants | 64 Participants | 50 Participants | 165 Participants |
| Race/Ethnicity, Customized White | 72 Participants | 175 Participants | 102 Participants | 349 Participants |
| Sex: Female, Male Female | 55 Participants | 109 Participants | 72 Participants | 236 Participants |
| Sex: Female, Male Male | 68 Participants | 130 Participants | 80 Participants | 278 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 55 / 123 | 171 / 239 | 90 / 152 |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 | 0 / 0 |
Outcome results
Primary
PFS: C1071003 Cohort A Versus COTA Cohort- Using Inverse Probability of Treatment Weights (IPTW)
PFS: a) C1071003 Cohort A: time from the date of the first dose until confirmed PD per IMWG criteria or death due to any cause, whichever occurred first; b) COTA: time from initiation of the first line after participant identified as having TCR MM to either the date of progression or death due to any cause, whichever occurred first. IMWG criteria for progression: an increase of \>=25% from the lowest response value in any 1 or more of the criteria: SPEP with an absolute increase \>0.5 g/dL; 24-hour UPEP with an absolute increase \>200 mg/24 h; in participants without measurable serum and urine M-protein, the absolute increase of \>10 mg/dL in the difference between involved and uninvolved FLC levels; or an absolute bone marrow plasma cell percentage \>10%. Retrospective data was retrieved and observed in the current study for approximately 1.5 months. Participants without an event were censored at date of last adequate disease assessment or the data cut-off. Kaplan Meier method was used.
Time frame: C1071003:First dose to confirmed PD/ death due to any cause or censoring whichever occurred first (maximum of 15 months);COTA:Initiation of first line post TCR MM to PD/ death due to any cause or censoring whichever occurred first (maximum of 64.3 months)
Population: Eligible participants whose data was retrieved and was used in this retrospective cohort study. In this outcome measure, IPTW analysis was applied. IPTW eliminated the effect of confounding by observed baseline participant characteristics, improve covariate balance, and thereby obtained unbiased estimates of treatment effects. IPTW created pseudo-sets, hence Number of Participants Analyzed (N) are different from participant flow and baseline section.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| C1071003 Cohort A | PFS: C1071003 Cohort A Versus COTA Cohort- Using Inverse Probability of Treatment Weights (IPTW) | NA Months |
| RWD: COTA | PFS: C1071003 Cohort A Versus COTA Cohort- Using Inverse Probability of Treatment Weights (IPTW) | 5.26 Months |
p-value: 0.000395% CI: [0.22, 0.64]Regression, Cox
Primary
PFS: Study C1071003 Cohort A Versus Flatiron Cohort - Using IPTW Analysis
PFS: a) C1071003 Cohort A, PFS: time from the date of the first dose until confirmed PD per IMWG criteria or death due to any cause, whichever occurred first. B) Flatiron Health: time from initiation of the first line after participant identified as having TCR MM to either the date of progression or death due to any cause, whichever occurred first. IMWG criteria for progression: an increase of \>= 25% from baseline/nadir value in any one or more of the following: an absolute increase in serum M-protein by SPEP by \>= 0.5 g/dL; serum M-protein \>= 1 g/dL if the lowest M component was \>= 5 g/dL; an absolute increase in urine M-protein by UPEP by \>=200 mg/24 h; in participants without measurable serum and urine M-protein levels, an absolute increase in the difference between involved and uninvolved FLC levels of \>10 mg/dL. Retrospective data was retrieved and observed in the current study for approximately 1.5 months. Kaplan Meier Method was used for analysis.
Time frame: C1071003:First dose to confirmed PD/death due to any cause or censoring whichever occurred first(maximum of 15 months);Flatiron:Initiation of first line post TCR MM to PD/death due to any cause or censoring,whichever occurred first(maximum of 66.9 months)
Population: Eligible participants whose data was retrieved and was used in this retrospective cohort study. IPTW analysis: eliminated the effect of confounding by observed baseline participant characteristics, improve covariate balance, and thereby obtained unbiased estimates of treatment effects. IPTW created pseudo-sets and N are different from participant and baseline section. Participants without an event were censored at date of last adequate disease assessment or the data cut-off.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| C1071003 Cohort A | PFS: Study C1071003 Cohort A Versus Flatiron Cohort - Using IPTW Analysis | NA Months |
| RWD: COTA | PFS: Study C1071003 Cohort A Versus Flatiron Cohort - Using IPTW Analysis | 2.79 Months |
Primary
PFS: Study C1071003 Cohort A Versus Flatiron Cohort - Using Unweighted Analysis
PFS: a) C1071003 Cohort A, PFS: time from the date of the first dose until confirmed PD per IMWG criteria or death due to any cause, whichever occurred first. B) Flatiron Health: time from initiation of the first line after participant identified as having TCR MM to either the date of progression or death due to any cause, whichever occurred first. IMWG criteria for progression: an increase of \>= 25% from baseline/nadir value in any one or more of the following: an absolute increase in serum M-protein by SPEP by \>= 0.5 g/dL; serum M-protein \>= 1 g/dL if the lowest M component was \>= 5 g/dL; an absolute increase in urine M-protein by UPEP by \>=200 mg/24 h; in participants without measurable serum and urine M-protein levels, an absolute increase in the difference between involved and uninvolved FLC levels of \>10 mg/dL. Retrospective data was retrieved and observed in the current study for approximately 1.5 months.
Time frame: C1071003:First dose to confirmed PD/death due to any cause or censoring whichever occurred first(maximum of 15 months);Flatiron:Initiation of first line post TCR MM to PD/death due to any cause or censoring,whichever occurred first(maximum of 66.9 months)
Population: Eligible participants whose data was retrieved and was used in this retrospective cohort study. Kaplan Meier Method was used for analysis. Participants without an event were censored at date of last adequate disease assessment or the data cut-off.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| C1071003 Cohort A | PFS: Study C1071003 Cohort A Versus Flatiron Cohort - Using Unweighted Analysis | NA Months |
| RWD: COTA | PFS: Study C1071003 Cohort A Versus Flatiron Cohort - Using Unweighted Analysis | 3.71 Months |
Primary
Progression Free Survival (PFS): Study C1071003 Cohort A Versus RWD COTA Cohort- Using Unweighted Analysis
PFS: a) C1071003 Cohort A: time from the date of the first dose until confirmed progressive disease (PD) per IMWG criteria or death due to any cause, whichever occurred first; b) RWD COTA: time from initiation of the first line after participant identified as having TCR MM to either the date of progression or death due to any cause, whichever occurred first. IMWG criteria for progression: an increase of \>=25% (Percent) from the lowest response value in any 1 or more of the criteria: serum protein electrophoresis (SPEP) with an absolute increase \>0.5 gram/deciliter (g/dL); 24-hour(h) urine protein electrophoresis (UPEP) with an absolute increase \>200 microgram (mg)/24 h; in participants without measurable serum and urine M-protein, the absolute increase of \>10 mg/dL in the difference between involved and uninvolved free light chain (FLC) levels; or an absolute bone marrow plasma cell \>10%. Retrospective data was retrieved and observed in the current study for approximately 1.5 months.
Time frame: C1071003:First dose to confirmed PD/ death due to any cause or censoring whichever occurred first (maximum of 15 months);COTA:Initiation of first line post TCR MM to PD/ death due to any cause or censoring whichever occurred first (maximum of 64.3 months)
Population: Eligible participants whose data was retrieved and was used in this retrospective cohort study. Kaplan Meier method was used for analysis. Participants without an event were censored at the date of last adequate disease assessment or the data cut-off.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| C1071003 Cohort A | Progression Free Survival (PFS): Study C1071003 Cohort A Versus RWD COTA Cohort- Using Unweighted Analysis | NA Months |
| RWD: COTA | Progression Free Survival (PFS): Study C1071003 Cohort A Versus RWD COTA Cohort- Using Unweighted Analysis | 4.70 Months |
p-value: <0.000195% CI: [0.37, 0.71]Regression, Cox
Secondary
OS: Study C1071003 Cohort A Versus Flatiron Cohort - Using IPTW Analysis
OS: a) C1071003 Cohort A: OS was defined as time from the date of the first dose until death due to any cause; B) Flatiron Cohort: OS was defined as time from initiation of the first line after participant identified as having TCR MM until the date of death due to any cause. Kaplan Meier Method was used for analysis. Participants without an event were censored at the latest available record or the data cut-off.
Time frame: C1071003: The date of the first dose until death due to any cause or censoring (maximum up to 15 months); Flatiron: First line after participant identified as having TCR MM until the date of death due to any cause or censoring (maximum of 66.9 months)
Population: Eligible participants whose data was retrieved and was used in this retrospective cohort study. In this outcome measure, IPTW analysis was applied. IPTW eliminated the effect of confounding by observed baseline participant characteristics, improve covariate balance, and thereby obtained unbiased estimates of treatment effects. IPTW created pseudo-sets and Number of Participants Analyzed are different from participant flow and baseline section.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| C1071003 Cohort A | OS: Study C1071003 Cohort A Versus Flatiron Cohort - Using IPTW Analysis | NA Months |
| RWD: COTA | OS: Study C1071003 Cohort A Versus Flatiron Cohort - Using IPTW Analysis | 11.24 Months |
Secondary
OS: Study C1071003 Cohort A Versus Flatiron Cohort - Using Unweighted Analysis
OS: a) C1071003 Cohort A: OS was defined as time from the date of the first dose until death due to any cause; B) Flatiron Cohort: OS was defined as time from initiation of the first line after participant identified as having TCR MM until the date of death due to any cause. Kaplan Meier Method was used for analysis. Participants without an event were censored at the latest available record or the data cut-off.
Time frame: C1071003: The date of the first dose until death due to any cause or censoring (maximum up to 15 months); Flatiron: First line after participant identified as having TCR MM until the date of death due to any cause or censoring (maximum of 66.9 months)
Population: Eligible participants whose data was retrieved and was used in this retrospective cohort study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| C1071003 Cohort A | OS: Study C1071003 Cohort A Versus Flatiron Cohort - Using Unweighted Analysis | NA Months |
| RWD: COTA | OS: Study C1071003 Cohort A Versus Flatiron Cohort - Using Unweighted Analysis | 11.24 Months |
Secondary
OS: Study C1071003 Cohort A Versus RWD COTA Cohort- Using IPTW Analysis
OS: a) C1071003 Cohort A: OS was defined as time from the date of the first dose until death due to any cause; b) COTA Cohort: OS was defined as time from initiation of the first line after participant identified as having TCR MM until the date of death due to any cause. Kaplan Meier Method was used for analysis. Participants without an event were censored at the latest available record or the data cut-off.
Time frame: C1071003: The date of the first dose until death due to any cause or censoring (maximum up to 15 months); COTA: First line after participant identified as having TCR MM until the date of death due to any cause or censoring (maximum of 64.3 months)
Population: Eligible participants whose data was retrieved and was used in this retrospective cohort study. In this outcome measure, IPTW analysis was applied. IPTW eliminated the effect of confounding by observed baseline participant characteristics, improve covariate balance, and thereby obtained unbiased estimates of treatment effects. IPTW created pseudo-sets and Number of Participants Analyzed are different from participant flow and baseline section.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| C1071003 Cohort A | OS: Study C1071003 Cohort A Versus RWD COTA Cohort- Using IPTW Analysis | NA Months |
| RWD: COTA | OS: Study C1071003 Cohort A Versus RWD COTA Cohort- Using IPTW Analysis | 11.24 Months |
p-value: 0.003295% CI: [0.27, 0.77]Regression, Cox
Secondary
Overall Survival (OS): Study C1071003 Cohort A Versus RWD COTA Cohort- Using Unweighted Analysis
OS: a) C1071003 Cohort A: OS was defined as time from the date of the first dose until death due to any cause; b) COTA Cohort: OS was defined as time from initiation of the first line after participant identified as having TCR MM until the date of death due to any cause. Kaplan Meier Method was used for analysis. Participants without an event were censored at the latest available record or the data cut-off.
Time frame: C1071003: The date of the first dose until death due to any cause or censoring (maximum up to 15 months); COTA: First line after participant identified as having TCR MM until the date of death due to any cause or censoring (maximum of 64.3 months)
Population: Eligible participants whose data was retrieved and was used in this retrospective cohort study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| C1071003 Cohort A | Overall Survival (OS): Study C1071003 Cohort A Versus RWD COTA Cohort- Using Unweighted Analysis | NA Months |
| RWD: COTA | Overall Survival (OS): Study C1071003 Cohort A Versus RWD COTA Cohort- Using Unweighted Analysis | 11.24 Months |
p-value: 0.006295% CI: [0.47, 0.88]Regression, Cox