Biomarkers in Multiple Myeloma

Study Overview
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Brief Summary
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The association between multiple myeloma (MM) and venous thromboembolism (VTE) is well known. Indeed, the incidence of VTE is increased in patients with newly diagnosed MM and in patients treated by immunomodulatory drugs in combination with glucocorticoids. Moreover, the clinical outcome of MM is supposed to be correlated to the risk of thrombosis. At the biological level, a number of hemostasis abnormalities participate in increasing VTE incidence. Yet, data on predictive biomarkers linked to VTE are limited.

Detailed Description
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There is a need to discern predictive biomarkers in order to better identify patients at risk of developing VTE, to decipher the mechanisms by which myeloma treatments interfere and in fine to choose an adequate thromboprophylaxis. In this context, it is important to document the precise expression of coagulation factors and to profile point-of-care tests for coagulation monitoring in newly diagnosed MM patients, before and during treatment. In addition, thromboprophylaxis is systematically included in therapeutic MM strategies, especially direct oral anticoagulants, without knowing whether potential drug interactions are occurring. This study aims at evaluating and validating predictive biomarkers of VTE in MM, and at identifying patients whose thromboprophylaxis is required and may potentially be adjusted because of drug interactions.

Official Title
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Evaluation of Predictive Biomarkers in de Novo Multiple Myeloma on the Onset of Venous Thromboembolism, Its Impact on Clinical Outcome and Thromboprophylaxis (VESICOM)

Conditions
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Hematological Patients, Newly Diagnosed Multiple Myeloma, Chemotherapy

Intervention / Treatment
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* Other: Blood samples


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient affiliated to a social security regimen or beneficiary of the same Signed written informed consent form Confirmed diagnosis of de novo multiple myeloma, non-previously treated and requiring treatment. Exclusion Criteria: Pregnant women Patient under guardianship or deprived of his liberty or any condition that may affect the patient's ability to understand and sign the informed consent Refusing participation Patient whose follow-up or life expectancy is less than 6 months.

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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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients with multiple myeloma<br>Adult patient, over 18 years old, with newly diagnosed multiple myeloma, indication of chemotherapy. | Other: Blood samples<br>* Peripheral blood sampling will be performed at different time points of the study, for a total volume of 20-40 mL: Sampling before MM treatment, Sampling during MM treatment (at 3 months post-initiation if no autograft or before autograft), Only for Patients treated with Apixaban or Eliquis®, 2 additional samplings during MM treatment for pharmacokinetics analysis.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Level of thrombin generation in newly diagnosed and untreated MM | Measurement of thrombin on plasma from newly diagnosed MM patients before the initiation of chemotherapy | 24 months | 
| Level of factor VIII in newly diagnosed and untreated MM | Measurement of factor VIII on plasma from newly diagnosed MM patients before the initiation of chemotherapy | 24 months | 
| Level of D-Dimers in newly diagnosed and untreated MM | Measurement of D-Dimers on plasma from newly diagnosed MM patients before the initiation of chemotherapy | 24 months | 
| Level of pro-coagulant phospholipids in newly diagnosed and untreated MM | Measurement of pro-coagulant phospholipids on plasma from newly diagnosed MM patients before the initiation of chemotherapy | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Association between biomarkers (thrombin, factor VIII, D-Dimers, pro-coagulant phospholipids) and VTE onset | Correlation between the plasma level of biomarkers and clinical data | 24 months | 
| Association between biomarkers (thrombin, factor VIII, D-Dimers, pro-coagulant phospholipids) and MM outcome | Correlation between the plasma level of biomarkers and clinical data | 24 months | 
| Evolution of biomarkers (thrombin, factor VIII, D-Dimers, pro-coagulant phospholipids) at 3 months post-treatment | Correlation between the plasma level of biomarkers and clinical data | 24 months | 
| Evaluation of the exposition of Apixaban (Eliquis®) | Plasma level of Apixaban in MM treated patients | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hematology, multiple myeloma, chemotherapy, thromboprophylaxis