A Study of Real Life Treatment for Multiple Myeloma (MM)

Study Overview
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Brief Summary
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The main aim of this study is to learn how long it takes for people with MM to have a relapse after their first treatment. Not all participants will have a relapse during the study. Participants will visit their clinic every 3 months and be treated according to their clinic's standard practice. The study sponsor will not be involved in how participants are treated but will provide instructions on how the clinics will record what happens during the study.

Detailed Description
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This is a non-interventional, prospective study of participants with MM relapses. This study will assess the low detection rate of biochemical relapses which will improve routine clinical practices and management of participants with MM in real world practice. The study will enroll approximately 350 participants. The data will be collected both prospectively and/or retrospectively at the specialized care (hematology) and will be recorded into electronic case report forms (e-CRFs) of the electronic data capture (EDC) system. All the participants will be assigned to a single observational cohort: • Participants With MM This multi-center study will be conducted in the Russian Federation. The overall duration of the study will be approximately 4 years. The overall time for treatment and follow-up period will be approximately 2.5 years for each participant.

Official Title
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Local, Multicentre, Non-Interventional Study of Early Diagnostics of Multiple Myeloma Relapses Evaluation in Real Life Practice in the Russian Federation

Conditions
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Multiple Myeloma

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: With newly diagnosed multiple myeloma (NDMM) eligible and non-eligible for a high-dose therapy and autologous stem cell transplantation (HDT-ASCT) who have had a response (defined as CR, VGPR, or PR) to the ongoing SoC induction (1st line) therapy that has been started within 3 months before the inclusion. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 at the time of inclusion. Exclusion Criteria: With NDMM eligible and non-eligible for a HDT-ASCT who have had SD or PD to the ongoing standard of care (SoC) induction (1st line) therapy that has been started within 3 months before the inclusion. Current, previous (within the last year) or planned (for the next 15-20 months) participation in interventional clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Participants With MM<br>Participants diagnosed with MM (complete response [CR], very good partial response [VGPR] and partial response [PR]) and who have received one prior first line treatment within 3 months preceding the enrollment, will be observed retrospectively and medical data will be monitored and collected prospectively every 3 months until the second biochemical and symptomatic relapse is identified. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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) | 
| Percentage of Participants With High β2-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) | 
| 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) | 
| 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) | 
| 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) | 
| Percentage of Participants With Circulating Plasma Cells 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) | 
| 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, β2-Microglobulin <3.5mg/L and albumin >=3.5g/dL, Stage II: not stage I or III, Stage III: high risk,β2-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) | 
| 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) | 
| 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) | 
| Number of Participants Reporting One or More Adverse Events (AEs) With First Line Therapy |  | Up to approximately 4 years | 
| Number of Participants Reporting One or More AEs With Second Line Therapy |  | Up to approximately 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug Therapy