Non-invasive MRD Assessment in Multiple Myeloma

Study Overview
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Brief Summary
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The purpose of this study is to investigate the sensitivity and accuracy of non-invasive MRD assessment using liquid biopsy (blood draw) and functional imaging (whole body MRI) in participants with new diagnosed and previously treated multiple myeloma. The long-term goal of this study is to investigate whether non-invasive methods for MRD assessment can replace bone marrow aspiration and biopsy in a substantial percentage of participants with multiple myeloma.

Detailed Description
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There is an unmet clinical need for an easier, non-invasive, and reliable method to perform MRD assessments that can be used in clinical trials and routine practice. The two non-invasive modalities that are most promising for MRD assessment are liquid biopsy to detect circulating tumor cells (CTCs) and functional imaging to detect focal myeloma lesions. However, there are no prospective data on the sensitivity and specificity of non-invasive MRD assessment with respect to the gold standard of bone marrow sampling.

Official Title
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Non-Invasive Minimal Residual Disease (MRD) Assessment in Multiple Myeloma Via Functional Imaging and Liquid Biopsy

Conditions
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Myeloma

Intervention / Treatment
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* Other: MRD Assessment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults age ≥18 years Patients with newly diagnosed multiple myeloma Patients with previously treated multiple myeloma with a maximum of two prior lines of therapy Expected life expectancy of greater than one year and intention to start a new line of treatment Exclusion Criteria: Patients without cognitive capacity to give informed consent for participation Patients with contraindications to MRI, which include the following: Claustrophobia, which, at investigator's discretion, would prohibit patient from undergoing whole body diffusion-weighted magnetic resonance imaging (WB-DWI) Pacemaker Metallic implants, which would prohibit patient from undergoing MRI All subjects will be screened for any contraindication to MRI as per their guidelines at the time of patient enrollment. Patients must not receive granulocyte colony stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) injection within 1 week prior to WB-DWI. Patients must not have been initiated on treatment prior to baseline disease assessment by bone marrow aspiration/biopsy and/or WB-DWI Up to 160 mg of dexamethasone (or equivalent) and/or 1 dose of bortezomib (+/- Cyclophosphamide-Dexamethasone) is allowed prior to disease assessment by bone marrow aspiration and WB-DWI.

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 |
| --- | --- |
| Myeloma Group<br>Patients with newly diagnosed and previously treated multiple myeloma will receive bone marrow sampling and functional imaging. | Other: MRD Assessment<br>* MRD assessment includes liquid biopsy and functional imaging. Liquid biopsy will be performed by the Adaptive ClonoSEQ® assay in peripheral blood. Functional imaging will be performed by whole body diffusion-weighted magnetic resonance imaging (WB-DWI).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity of non-invasive MRD assessment | MRD assessment includes liquid biopsy and functional imaging. | 6 months | 
| Specificity of non-invasive MRD assessment | MRD assessment includes liquid biopsy and functional imaging. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity of two MRD-testing algorithms | Combining liquid biopsy, functional imaging, and bone marrow sampling against the reference of bone marrow sampling in patients | 6 months | 
| Specificity of two MRD-testing algorithms | Combining liquid biopsy, functional imaging, and bone marrow sampling against the reference of bone marrow sampling in patients | 6 months | 
| Progression Free Survival | The progression-free survival (PFS) will be calculated of patients who are MRD-positive and MRD-negative on each modality (liquid biopsy, functional imaging, and bone marrow sampling) | 2 years | 
| Overall Survival | The overall survival (OS) will be calculated of patients who are MRD-positive and MRD-negative on each modality (liquid biopsy, functional imaging, and bone marrow sampling) | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liquid biopsy, Minimal Residual Disease (MRD), Functional imaging