Real-world Use of Carfilzomib Among Multiple Myeloma Patients in Europe

Study Overview
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Brief Summary
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With the recent addition of carfilzomib as a treatment option for multiple myeloma, no data is available yet on how the drug is being used outside of the clinical trial setting. This study will therefore provide essential data to demonstrate the real world utilization of carfilzomib in routine clinical practice, including dosage, administration schedule, regimen, duration of treatment and reason for discontinuation in Europe.

Detailed Description
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With the recent addition of carfilzomib as a treatment option for multiple myeloma, no data is available yet on how the drug is being used outside of the clinical trial setting. The Primary Objective is to describe carfilzomib utilisation in routine clinical practice, including dosage, administration schedule, regimen, duration of treatment and reason for discontinuation. Secondary Objectives: Describe the population treated with carfilzomib in terms of demographics, multiple myeloma (MM) disease characteristics, treatment history, and comorbidities. Describe the safety profile of carfilzomib in routine clinical practice. Describe response to treatment as assessed by the physician and recorded in the medical file. Describe healthcare resource utilisation of subjects treated with carfilzomib, in terms of unplanned hospitalisations. Describe the reasons for choosing carfilzomib as the MM treatment of choice. Describe specific concomitant therapy (bisphosphonates, thromboprophylaxis, antihypertensive treatment, anti-infective treatment) and whether these therapies were used as prophylaxis or as treatment. Describe a cardiovascular assessment at carfilzomib regimen initiation and at occurrence of cardiac adverse events, where available per routine care (electrocardiogram [ECG], echocardiography, left ventricular ejection fraction).

Official Title
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Real-world Use of Carfilzomib Among Multiple Myeloma Patients in Europe Who Have Received at Least One Prior Therapy.

Conditions
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Multiple Myeloma

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or older at the time of carfilzomib initiation At least one prior line of MM treatment has been received Carfilzomib treatment has been initiated per routine practice and is currently ongoing At least one administration of carfilzomib in a combination regimen (ie, not monotherapy) has been received Provided written informed consent prior to abstraction of any data, in countries where written informed consent is required. Subjects who previously completed treatment with carfilzomib in a clinical trial, a compassionate use program or through routine practice, are eligible to take part in the study. Subjects who receive radiotherapy concurrently with carfilzomib treatment are also eligible to take part in the study. Subjects who initiate carfilzomib treatment on a combination regimen, subsequently discontinue all concomitant medications but remain on carfilzomib monotherapy in later cycles, remain eligible for participation in the study. Subjects who are also enrolled in other observational studies in which standard of care is not altered are eligible to take part in the study, Exclusion Criteria: Subjects who are enrolled in a carfilzomib clinical trial will not be eligible to additionally take part in this observational study. Subjects who are receiving carfilzomib treatment within a compassionate use program will not be eligible to take part in this observational study. If a subject who has enrolled into this observational study, also enrolls in a clinical trial in which MM treatment and/or disease management is protocol-specified, the subject becomes ineligible and the subject's data will be censored from the time the subject enrolled the 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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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Carfilzomib starting dose | Carfilzomib dose at first administration | 18 months | 
| Carfilzomib dose | Carfilzomib dose at subsequent administrations | 18 months | 
| Carfilzomib dose modification | Modification includes change in dose level, dose interruption, and dose delays | 18 months | 
| Time to carfilzomib dose modification | At least one carfilzomib dose modification, escalation or reduction | 18 months | 
| Reason for dose modification | Reason for dose modification or delay | 18 months | 
| Number of cycles started | Number of carfilzomib treatment cycles started throughout study period | 18 months | 
| Carfilzomib regimen | Treatment combination | 18 months | 
| Carfilzomib dosing frequency | Number of administrations per cycle | 18 months | 
| Carfilzomib dosing schedule | Timing of carfilzomib administration within treatment cycle | 18 months | 
| Carfilzomib duration of treatment | Duration of carfilzomib treatment | 18 months | 
| Starting dose of concomitant anti-myeloma agents | Dose of combination agents (e.g. lenalidomide or dexamethasone) at baseline | 18 months | 
| Dose modification for concomitant anti-myeloma agents | Modification includes change in dose level, dose interruption, and dose delays | 18 months | 
| Reason for frequency modification | At least 1 change in frequency of carfilzomib administration. | 18 months | 
| Reason for change in frequency of concomitant multiple myeloma therapies | Reason for change in frequency of administration. | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| International Staging System (ISS) score and revised ISS stage at diagnosis and carfilzomib regimen initation | International Staging System (ISS) score of I, II, III, or unkown | 18 months | 
| Eastern Cooperative Oncology Group (ECOG) performance status | ECOG performance status category at multiple myeloma diagnosis and carfilzomib regimen initiation. | 18 months | 
| Cytogenetic risk profile at diagnosis | Cytogenetic risk profile at diagnosis | 18 months | 
| Presence of CRAB features (i.e. hypercalcemia, renal insufficiency, anemia and/or bone pain) | Presence of CRAB features at MM diagnosis | 18 months | 
| Presence of comorbidities | Diagnosed at any point in time before carflzomib regimen initiation | 18 months | 
| Previously received anti-myeloma treatment | Treatment history | 18 months | 
| Response to prior treatment | Response to prior treatment received before initiation of carfilzomib | 18 months | 
| Number of prior relapses | Type of relapse (molecular, hematologic, or symptomatic) | 18 months | 
| Adverse event | All grade 3 or above adverse events. | 18 months | 
| Time to adverse event | All grade 3 or above adverse events | 18 months | 
| Electrocardiogram (ECG) changes | ECG changes as recorded in tests performed per routine practice | 18 months | 
| Decrease in left ventricular ejection fraction (LVEF) | LVEF decrease as recorded in tests performed per routine practice | 18 months | 
| Initiation or dose increase of antihypertensive treatment | Initiation or dose increase of existing antihypertensive treatment | 18 months | 
| Initiation or dose increase of existing heart failure treatment | Initiation or dose increase of existing heart failure treatment | 18 months | 
| Response to carfilzomib treatment | Physician-assessed response as recorded on the medical charts | 18 months | 
| Type of relapse | Molecular, hematologic or symptomatic relapse | 18 months | 
| Number of unplanned hospitalisations | Initiation or dose increase of existing heart failure treatment | 18 months | 
| Concomitant therapy not part of the carfilzomib regimen | Concomitant therapy not part of the carfilzomib regimen | 18 months | 
| Planned subsequent treatment regimen | Planned subsequent treatment regimen catergory | 18 months | 
| Patient age | Patient age | 18 months | 
| Patient sex | Patient sex | 18 months | 
| Patient height | Patient height | 18 months | 
| Patient weight | Patient weight | 18 months | 
| MRI (magnetic resonance imaging) performed at MM diagnosis and carfilzomib regimen initiation. | MRI (magnetic resonance imaging) | 18 months | 
| PET-CT (positron emission tomography-computed tomography) performed at MM diagnosis and carfilzomib regimen initiation. | PET-CT (positron emission tomography-computed tomography) | 18 months | 
| Measurement of Serum M component at MM diagnosis and carfilzomib regimen initiation. | Serum M component | 18 months | 
| Measurement of Urine M component at MM diagnosis and carfilzomib regimen initiation. | Urine M component | 18 months | 
| Measurement of serum albumin at MM diagnosis and carfilzomib regimen initiation. | Serum albumin | 18 months | 
| Measurement of serum beta-2-microglobulin at MM diagnosis and carfilzomib regimen initiation. | Beta-2-microglobulin | 18 months | 
| Measurement of percent of plasma cells in bone marrow at MM diagnosis and carfilzomib regimen initiation. | Percent of plasma cells in bone marrow | 18 months | 
| Baseline measurement of lactate dehydrogenase at MM diagnosis and carfilzomib regimen initiation. | Lactate dehydrogenase | 18 months | 
| ECG (electrocardiogram) | ECG (electrocardiogram) | 18 months | 
| Echocardiogram | Echocardiogram | 18 months | 
| LVEF (left ventricular ejection fraction) assessment | LVEF (left ventricular ejection fraction) assessment | 18 months | 
| Computed Tomography (CT) performed at MM diagnosis and carfilzomib regiment initiation. | Computed tomography | 18 Months | 
| Myeloma/Osteolytic lesions detected by MRI, PET-CT, and X-ray at MM diagnosis and carfilzomib regimen initiation | Myeloma/Osteolytic lesions detected by MRI, PET-CT, and X-ray at MM diagnosis and carfilzomib regimen initiation | 18 months |