Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| Primary |
Median Time From the Start of First Line Therapy of Participants With MM to First Biochemical Relapse of MM |
According to the International Myeloma Working Group (IMWG), biochemical relapse is diagnosed in participants with relapsing MM based on the following criteria: increase in serum paraprotein by at least 25 percent (%) of nadir (absolute increase should be at least greater than or equal to [>=] 0.5 gram per liter [g/L]), increase in urine paraprotein by at least 25% (absolute increase of at least >=200 milligram per 24 hours [mg/24 h]), more than 25% increase in the difference between involved and non-involved free light chains (FLC) with abnormal FLC ratio and absolute increase of at least greater than (>) 10 milligram per deciliter (mg/dL), increase in plasmacyte infiltration by least >=10% in participants with non-secretory MM. |
From the start of the first line therapy until first biochemical relapse (up to approximately 4 years) |
|
| Secondary |
Median Time From the Start of First Line Therapy of Participants With MM to First Biochemical Relapse of MM in the Determined Subgroups |
As per IMWG, biochemical relapse diagnosed with relapsing MM on following criteria: increase in serum paraprotein by at least 25% of nadir (absolute increase should be at least >=0.5 g/L, increase in urine paraprotein by at least 25% (absolute increase of at least >=200 mg/24 h, >25% increase in difference between involved and non-involved FLC with abnormal FLC ratio and absolute increase of at least >10 mg/dL, increase in plasmacyte infiltration by least >=10% with non-secretory MM. Subgroups for analysis: MM International Staging System (ISS) stages: I, II, III; Myeloma frailty score (MFS): 0 and 1 vs 2 and more;Cytogenetic risk: high-risk vs standard risk;Best response during 1st line treatment: a PR a CR or VGPR;Performance status: Eastern Cooperative Oncology Group (ECOG) = 0-1 vs ECOG = 2;Autologous Stem Cell Transplant (ASCT) vs non-ASCT receivers; Maintenance therapy; Treatment regimens of 1st line |
From the start of the first line therapy until first biochemical relapse (up to approximately 4 years) |
|
| Secondary |
Median Time From the Start of First Line Therapy of Participants With MM |
Clinical relapse is confirmed when one or more of the following criteria (CRAB-criteria: MM-associated symptoms: hypercalcemia, renal failure, anemia, bone disease criteria). Hypercalcemia (>2.75 millimole per liter [mmol/L] or >11.5 mg/dL); renal failure: serum creatinine level >2 mg/dL (>173 mmol/L); anemia: normochromic normocytic anemia with hemoglobin level by less than (<) 2 g/dL (20 milligram per liter [mg/L]) less than the lower limit of the normal level or hemoglobin level <10 g/dL (<100 gram per liter [g/L]); bone lesions (lytic lesions, severe osteopenia, compression fractures). Subgroups for analysis: MM ISS stages: I, II, III; MFS: 0 and 1 vs 2 and more;Cytogenetic risk: high-risk vs standard risk; Best response during 1st line treatment: a PR* a CR8 or VGPR9; Performance status: ECOG = 0-1 vs ECOG = 2, ASCT vs non-ASCT receivers, Maintenance therapy; Treatment regimens of 1st line. |
From the start of the first line therapy until first symptomatic relapse (up to approximately 4 years) |
|
| Secondary |
Median Time From the Start of Second Line Therapy of Participants With MM to Second Biochemical Relapse of MM |
According to IMWG, biochemical relapse is diagnosed in participants with relapsing MM based on following criteria: increase in serum paraprotein by at least 25% of nadir (absolute increase should be at least >=0.5 g/L), increase in urine paraprotein by at least 25% (absolute increase of at least >=200 mg/24 h), more than 25% increase in difference between involved and non-involved FLC with abnormal FLC ratio and absolute increase of at least >10 mg/dL, increase in plasmacyte infiltration by least >=10% in participants with non-secretory MM. Subgroups for analysis: MM ISS stages: I, II, III; MFS: 0 and 1 vs 2 and more;Cytogenetic risk: high-risk vs standard risk; Best response during 1st line treatment: a PR a CR or VGPR; Performance status: ECOG = 0-1 vs ECOG = 2, ASCT vs non-ASCT receivers; Maintenance therapy; Treatment regimens of 1st line;Therapeutic regimens of 2nd line (Rd, VRD, KRd, IxaRd, DaraRd, EloRd, other). |
From the start of the second line therapy until second biochemical relapse (up to approximately 4 years) |
|
| Secondary |
Median Time From the Start of Second Line Therapy of Participants With MM to Second Symptomatic Relapse of MM |
Clinical relapse is confirmed when one or more of the following criteria (CRAB-criteria: MM-associated symptoms, including hypercalcemia, renal failure, anemia, bone disease criteria) are found. Hypercalcemia (>2.75 mmol/L or >11.5 mg/dL), renal failure: serum creatinine level >2 mg/dL (>173 mmol/L), anemia: normochromic normocytic anemia with hemoglobin level by <2 g/dL (20 mg/L) less than the lower limit of the normal level or hemoglobin level <10 g/dL (<100 g/L), bone lesions (lytic lesions, severe osteopenia, compression fractures). Subgroups for analysis: MM ISS stages: I, II, III; MFS: 0 and 1 vs 2 and more;Cytogenetic risk: high-risk vs standard risk; Best response during 1st line treatment: a PR a CR or VGPR; Performance status: ECOG = 0-1 vs ECOG = 2, ASCT vs non-ASCT receivers; Maintenance therapy; Treatment regimens of 1st line;Therapeutic regimens of 2nd line (Rd, VRD, KRd, IxaRd, DaraRd, EloRd, other). |
From the start of the second line therapy until second symptomatic relapse (up to approximately 4 years) |
|
| Secondary |
PFS1L: Progression-free Survival (PFS) From the Start of first Line Therapy to the First Biochemical Relapse |
PFS1L:interval from start of 1st line therapy to 1st significant biochemical relapse. As per IMWG, biochemical relapse diagnosed in participants with relapsing MM on following criteria: increase in serum paraprotein by at least 25% of nadir (absolute increase should be at least >=0.5 g/L, increase in urine paraprotein by at least 25% (absolute increase of at least >=200 mg/24 h, >25% increase in difference between involved and non-involved FLC with abnormal FLC ratio and absolute increase of at least >10 mg/dL, increase in plasmacyte infiltration by least >=10% with non-secretory MM. Subgroups for analysis: MM ISS stages: I, II, III; MFS: 0 and 1 vs 2 and more;Cytogenetic risk: high-risk vs standard risk; Best response during 1st line treatment: a PR a CR or VGPR; Performance status: ECOG = 0-1 vs ECOG = 2, ASCT vs non-ASCT receivers; Maintenance therapy; Treatment regimens of 1st line. |
From the start of the first line therapy until first significant biochemical relapse or until the disease progression or death due to any reason whichever occurs first (up to approximately 4 years) |
|
| Secondary |
PFS2L: Progression-free Survival From the Start of Second Line Therapy to the Second Biochemical Relapse |
PFS2L: interval from start of 2nd line therapy to 2nd significant biochemical relapse. As per IMWG, biochemical relapse diagnosed in participants with relapsing MM on following criteria: increase in serum paraprotein by at least 25% of nadir (absolute increase should be at least >=0.5 g/L, increase in urine paraprotein by at least 25% (absolute increase of at least >=200 mg/24 h, >25% increase in difference between involved and non-involved FLC with abnormal FLC ratio and absolute increase of at least >10 mg/dL, increase in plasmacyte infiltration by least >=10% with non-secretory MM. Subgroups for analysis: MM ISS stages: I, II, III; MFS: 0 and 1 vs 2 and more;Cytogenetic risk: high-risk vs standard risk; Best response during 1st line treatment: a PR a CR or VGPR; Performance status: ECOG = 0-1 vs ECOG = 2, ASCT vs non-ASCT receivers; Maintenance therapy; Treatment regimens of 1st line;Therapeutic regimens of 2nd line (Rd, VRD, KRd, IxaRd, DaraRd, EloRd, other). |
From the start of the second line therapy until second significant biochemical relapse or until the disease progression or death due to any reason whichever occurs first (up to approximately 4 years) |
|
| Secondary |
DOT1: Duration of the First Line Therapy |
DOT1 is defined as time from initiation of the first drug to discontinuation of the last drug in the frame of first line of therapy. Subgroups for analysis: MM ISS stages: I, II, III; MFS: 0 and 1 vs 2 and more;Cytogenetic risk: high-risk vs standard risk; Best response during 1st line treatment: a PR a CR or VGPR; Performance status: ECOG = 0-1 vs ECOG = 2, ASCT vs non-ASCT receivers; Maintenance therapy; Treatment regimens of 1st line. |
From initiation of the first drug to discontinuation of the last drug in the frame of first line therapy (approximately 4 years) |
|
| Secondary |
DOMT1: Duration of 1st Line Maintenance Therapy |
DOMT1 is defined as the treatment duration of first line maintenance therapy. Subgroups for analysis: MM ISS stages: I, II, III; MFS: 0 and 1 vs 2 and more;Cytogenetic risk: high-risk vs standard risk; Best response during 1st line treatment: a PR a CR or VGPR; Performance status: ECOG = 0-1 vs ECOG = 2, ASCT vs non-ASCT receivers; Maintenance therapy; Treatment regimens of 1st line. |
From initiation of the first line maintenance therapy to discontinuation of the last drug in the frame of first line maintenance therapy (approximately 4 years) |
|
| Secondary |
DOT2: Duration of the Second Line Therapy |
DOT2 is defined as time from initiation of the first drug to discontinuation of the last drug in the frame of second line of therapy. Subgroups for analysis: MM ISS stages: I, II, III; MFS: 0 and 1 vs 2 and more;Cytogenetic risk: high-risk vs standard risk; Best response during 1st line treatment: a PR a CR or VGPR; Performance status: ECOG = 0-1 vs ECOG = 2, ASCT vs non-ASCT receivers; Maintenance therapy; Treatment regimens of 1st line;Therapeutic regimens of 2nd line (Rd, VRD, KRd, IxaRd, DaraRd, EloRd, other). |
From initiation of the first drug to discontinuation of the last drug in the frame of second line therapy (approximately 4 years) |
|
| Secondary |
PR1L: Percentage of Participants With Partial Response After First Line Therapy |
PR is defined as >=50% reduction of serum M protein and >=90% or <200 mg reduction urinary M protein in 24-hour, or >50% decrease in difference between involved and uninvolved FLC levels, or >50% reduction in bone marrow plasma cells, if bone marrow plasma cells >30% and >50% reduction in size of soft tissue plasmacytomas at baseline. Subgroups for analysis: MM ISS stages: I, II, III; MFS: 0 and 1 vs 2 and more;Cytogenetic risk: high-risk vs standard risk; Best response during 1st line treatment: a PR a CR or VGPR; Performance status: ECOG = 0-1 vs ECOG = 2, ASCT vs non-ASCT receivers; Maintenance therapy; Treatment regimens of 1st line. |
From the end of the first line therapy up to approximately 4 years |
|
| Secondary |
VGPR1L: Percentage of Participants With VGPR After First Line Therapy |
VGPR defined as >90% reduction (<100 mg/24-hour) in serum M-protein + urine M-protein detectable by immunofixation but not on electrophoresis. Subgroups for analysis: MM ISS stages: I, II, III; MFS: 0 and 1 vs 2 and more;Cytogenetic risk: high-risk vs standard risk; Best response during 1st line treatment: a PR a CR or VGPR; Performance status: ECOG = 0-1 vs ECOG = 2, ASCT vs non-ASCT receivers; Maintenance therapy; Treatment regimens of 1st line. |
From the end of the first line therapy up to approximately 4 years |
|
| Secondary |
CR1L: Percentage of Participants With Complete Response After First Line Therapy |
Complete response is defined as >5% plasma cells in myelogram with absence of paraprotein in serum and urine according to immunofixation. Subgroups for analysis: MM ISS stages: I, II, III; MFS: 0 and 1 vs 2 and more;Cytogenetic risk: high-risk vs standard risk; Best response during 1st line treatment: a PR a CR or VGPR; Performance status: ECOG = 0-1 vs ECOG = 2, ASCT vs non-ASCT receivers; Maintenance therapy; Treatment regimens of 1st line. |
From the end of the first line therapy up to approximately 4 years |
|
| Secondary |
ORR2L: Percentage of Participants With Objective Response Rate After the Second Line Therapy |
ORR2L: percentage of participants with CR, VGPR or PR assessed by IMWG to 2nd line therapy. Per IMWG criteria, CR: >5% plasma cells in myelogram with absence of paraprotein in serum and urine according to immunofixation; VGPR: >90% reduction (<100 mg/24-h) in serum M-protein + urine M-protein detectable by immunofixation but not on electrophoresis; PR: >=50% reduction of serum M protein and >=90% or <200 mg reduction urinary M protein in 24-hour, or >50% decrease in difference between involved and uninvolved FLC levels, or >50% reduction in bone marrow plasma cells, if bone marrow plasma cells >30% and >50% reduction in size of soft tissue plasmacytomas at baseline. Subgroups for analysis: MM ISS stages: I, II, Ill; MFS: 0 and 1 vs 2 and more;Cytogenetic high-risk vs standard risk; Best response during 1st line treatment;ECOG = 0-1 vs 2, ASCT vs non-ASCT receivers;Maintenance therapy;1st and 2nd line Treatment regimens. |
From the end of the second line therapy up to approximately 4 years |
|
| Secondary |
SD2L: Percentage of Participants With Stable Disease After the Second Line Therapy |
Stable disease (SD) is defined as any state that does not meet PR, VGPR, CR, or progressive disease (PD) criteria. Subgroups for analysis: MM ISS stages: I, II, III; MFS: 0 and 1 vs 2 and more;Cytogenetic risk: high-risk vs standard risk; Best response during 1st line treatment: a PR a CR or VGPR; Performance status: ECOG = 0-1 vs ECOG = 2, ASCT vs non-ASCT receivers; Maintenance therapy; Treatment regimens of 1st line;Therapeutic regimens of 2nd line (Rd, VRD, KRd, IxaRd, DaraRd, EloRd, other). |
From the end of second line therapy up to approximately 4 years |
|
| Secondary |
PD2L: Percentage of Participants With Progressive Disease After Second Line Therapy |
PD: increase in M-gradient by >=25% of least achieved serum (increase by >=5 g/L), urine (increase by >=200 mg/24 h) levels. With disease, "unmeasurable" by standard immunochemistry, but "measurable" by FLC level, progression: stated with increase in difference between involved and non-involved FLC by 100 mg/L. Progression: increase in bone marrow plasmatic cells level (absolute count-not less than by 10%), occurrence of new bone lesions or increase in size of previously detected ones, occurrence of new soft tissue plasmocytomas or increase in its size, hypercalcemia (corrected serum calcium level >11.5 mg/dL or 2.65 mmol/L) may be related to proliferation. Subgroups for analysis: MM ISS stages: I, II, Ill; MFS: 0 and 1 vs 2 and more;Cytogenetic high-risk vs standard risk; Best response during 1st line treatment;ECOG = 0-1 vs 2, ASCT vs non-ASCT receivers;Maintenance therapy;1st and 2nd line Treatment regimens. |
From the end of second line therapy up to approximately 4 years |
|
| Secondary |
Percentage of Participants With High-risk Cytogenetic Disorders at the Time of the First Symptomatic Relapse |
High-risk Cytogenetic Disorder is defined as risk according to cytogenetic profile at relapse (t[4;14], del (17p), amp (1q21), hypodiploidy) at the time of the first symptomatic relapse. |
From the start of the first line therapy until first symptomatic relapse (up to approximately 4 years) |
|
| Secondary |
Percentage of Participants With High ß2-microglobulin (ß2M) or Low Albumin Levels at the Time of the First and Second Symptomatic Relapse |
ß2M levels is defined as >5.5 mg/L and low albumin levels is defined as <3.5 g/dL at first symptomatic relapse. |
From the start of the first line therapy until first symptomatic relapse (for first symptomatic relapse) and until second symptomatic relapse (for second symptomatic relapse) (up to approximately 4 years) |
|
| Secondary |
Percentage of Participants With Extramedullary Lesions at the Time of the First and Second Symptomatic Relapse |
|
From the start of the first line therapy until first symptomatic relapse (for first symptomatic relapse) and until second symptomatic relapse (for second symptomatic relapse) (up to approximately 4 years) |
|
| Secondary |
Percentage of Participants With Lactate Dehydrogenase (LDH) Levels Above Normal at the Time of the First and Second Symptomatic Relapse |
|
From the start of the first line therapy until first symptomatic relapse (for first symptomatic relapse) and until second symptomatic relapse (for second symptomatic relapse) (up to approximately 4 years) |
|
| Secondary |
Percentage of Participants With Short Duration of Response or PD During Therapy at the Time of the First and Second Symptomatic Relapse |
PD is defined as increase in M-gradient by >=25% of least achieved serum (increase by >=5 g/L), urine (increase by >=200 mg/24 h) levels. For participants with disease, "unmeasurable" by standard immunochemistry, but "measurable" by FLC level, progression is stated with increase in difference between involved and non-involved FLC by 100 mg/L. Progression is also indicated by increase in bone marrow plasmatic cells level (absolute count - not less than by 10%), occurrence of new bone lesions or increase in size of previously detected ones, occurrence of new soft tissue plasmocytomas or increase in it's size, hypercalcemia (corrected serum calcium level >11.5 mg/dL or 2.65 mmol/L) that may be related to proliferation. Short duration of response <6 months. |
From the start of the first line therapy until first symptomatic relapse (for first symptomatic relapse) and until second symptomatic relapse (for second symptomatic relapse) (up to approximately 4 years) |
|
| Secondary |
Percentage of Participants With Circulating Plasma Cells at the Time of the First and Second Symptomatic Relapse |
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From the start of the first line therapy until first symptomatic relapse (for first symptomatic relapse) and until second symptomatic relapse (for second symptomatic relapse) (up to approximately 4 years) |
|
| Secondary |
Percentage of Participants With ISS stages II/III at the Time of the First and Second Symptomatic Relapse |
ISS is a measuring scale having three stages Stage I:low risk, ß2-Microglobulin <3.5mg/L and albumin >=3.5g/dL, Stage II: not stage I or III, Stage III: high risk,ß2-Microglobulin >=5.5mg/L. |
From the start of the first line therapy until first symptomatic relapse (for first symptomatic relapse) and until second symptomatic relapse (for second symptomatic relapse) (up to approximately 4 years) |
|
| Secondary |
Percentage of Participants With Isotypic Transformation at the Time of the First and Second Symptomatic Relapse |
Isotypic Transformation is defined as change in the type of secretion of light chains, hypersecretory disease. |
From the start of the first line therapy until first symptomatic relapse (for first symptomatic relapse) and until second symptomatic relapse (for second symptomatic relapse) (up to approximately 4 years) |
|
| Secondary |
Percentage of Participants With First and Second Symptomatic Relapse who Have Aggressive Clinical Disease Manifestations |
Aggressive clinical disease manifestations include the rapid development/quick start of symptoms manifestations, an advanced diseases stages based on the laboratory results, radiography or pathomorphological examinations, organ failure (disease-related organ disorder). |
From the start of the first line therapy until first symptomatic relapse (for first symptomatic relapse) and until second symptomatic relapse (for second symptomatic relapse) (up to approximately 4 years) |
|
| Secondary |
Number of Participants Reporting One or More Adverse Events (AEs) With First Line Therapy |
|
Up to approximately 4 years |
|
| Secondary |
Number of Participants Reporting One or More AEs With Second Line Therapy |
|
Up to approximately 4 years |
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