Multiple Myeloma Molecular Monitoring Study

Study Overview
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Brief Summary
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The investigators will track 250 multiple myeloma patients across Canada over time, using new lab tests to evaluate their blood and bone marrow, as they receive standard of care treatment. The main hypothesis is that these tests will allow clinicians to better diagnose and manage multiple myeloma, improving patients' quality of life overall.

Detailed Description
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Multiple myeloma (MM) is a deadly cancer of the bone marrow that is challenging to manage and treat: the drugs that are currently available attack the cancer in the same way for everyone, but each patient has different types of MM cancer cells and different family traits that predict better or worse outcomes. As well, the ways in which clinicians test to see if the cancer is in remission are not very good at detecting small numbers of cancer cells still in the bone marrow after treatment - and which will, sooner or later cause the patient to get sick again. The goal of the M4 study is to improve MM patients' survival and quality of life over time, by finding better ways of a) characterizing each patient's experience with the disease, and b) identifying and tracking the small numbers of cells that remain after treatment. The investigators plan to track 250 patients across Canada over time, who are getting treatment for multiple myeloma. While they are getting treatment, the research team will evaluate samples of their blood and bone marrow with newer, more precise laboratory tests. Participants will also be asked to take part in two scans of their bodies during their treatment. The investigators hypothesize that these tests can help clinicians make better treatment recommendations to patients. The investigators will look at whether one test is better than another, or if a combination of these tests is needed to have the best information possible to make treatment decisions. At the same time, the research will also explore how and why some patients' cancer becomes resistant to the treatments over time, and how myeloma cells are able to start growing again after treatment. The research team will also collect information on how each patient's health and quality of life changes during and after treatment, and what are the associated costs with these new approaches - to both the healthcare system overall, and to patients. Once the five-year research program is complete, it is hoped that clinicians will have a new, proven and affordable process of combining these new laboratory tests with the current clinical approach, to create new options to evaluate and treat multiple myeloma. It is the overall goal that this research will make a difference, right away and across the world, in how doctors treat multiple myeloma, in how it is studied by scientists, and in how patients advocate for their own healthcare.

Official Title
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The Terry Fox Pan-Canadian Multiple Myeloma Molecular Monitoring Study

Conditions
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Multiple Myeloma

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to give informed consent Diagnosed with active multiple myeloma Consented to participation in Myeloma Canada Research Network (MCRN) database project Previously untreated and eligible for autologous stem-cell transplantation (ASCT) Exclusion Criteria: Ineligible for ASCT Does not consent to participate in MCRN database project

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 99 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 |
| --- | --- | --- |
| Sensitivity of Minimal Residual Disease (MRD) Assays | Comparison of the sensitivity of two leading-edge MRD assays - (1) multiparameter flow cytometry (MFC), and (2) immunoglobulin gene sequencing (IgS) - in patients who meet the conventional definition of complete remission post-treatment. | 100 days post-treatment | 
| Sensitivity of Minimal Residual Disease (MRD) Assays | Comparison of the sensitivity of two leading-edge MRD assays - (1) multiparameter flow cytometry (MFC), and (2) immunoglobulin gene sequencing (IgS) - in patients who meet the conventional definition of complete remission post-treatment. | 12 months post-maintenance therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of Sensitivity of MRD Assays with PET scans | Comparison of the sensitivity of two MRD assays - (1) multiparameter flow cytometry (MFC), and (2) immunoglobulin gene sequencing (IgS) - with (3) positron emission tomography (PET) imaging scans, in order to determine if PET scans offer additional information above and beyond that offered through the two assays. | 12 months post-maintenance therapy | 
| Predicting Progression-Free Survival Using MRD Assessment | Establish the prognostic significance of MRD assessment (i.e., the two MRD assays, and PET scans) on progression-free survival | 5 years | 
| Predicting Overall Survival Using MRD Assessment | Establish the prognostic significance of MRD assessment (i.e., the two MRD assays, and PET scans) on overall survival | 5 years | 
| Quality-Adjusted Life Years (QALYs) Gained | To fully understand health care costs and benefits associated with personalized risk-adapted testing and monitoring strategies for cancer, compared to current standard of care (e.g., non-personalized), the investigators will create a model that includes cohort's responses on patient-reported health status (using the EuroQol-5D or EQ-5D-L) and use of healthcare resources (using the NCIC Resource Utilization Form), and that will calculate quality-adjusted life years of the participants. | 5 years | 
| Incremental Cost-Effectiveness of MRD Testing | To fully understand health care costs and benefits associated with personalized risk-adapted testing and monitoring strategies for cancer, compared to current standard of care (e.g., non-personalized), the investigators will create a model that includes cohort's responses on patient-reported health status (using the EuroQol-5D or EQ-5D-L) and use of healthcare resources (using the NCIC Resource Utilization Form), and that will calculate the cost-effectiveness of the MRD assays under investigation. | 5 years | 
| Productivity Costs Associated with MRD Testing | To fully understand health care costs and benefits associated with personalized risk-adapted testing and monitoring strategies for cancer, compared to current standard of care (e.g., non-personalized), the investigators will create a model that includes cohort's responses on patient-reported health status (using the EuroQol-5D or EQ-5D-L) and use of healthcare resources (using the NCIC Resource Utilization Form), and that will calculate the individual and system-level productivity costs associated with the MRD assays under investigation. | 5 years | 
| Multiple Myeloma Patients' Quality of Life (QOL) | The investigators will evaluate patients' QOL, especially how it is impacted by treatment, disease and patient characteristics, using a common self-report measure (European Organization for Research and Treatment of Cancer - Quality of Life Questionnaire, or EORTC-QLQ-30). Specific outcomes include QOL at each time point in the study and overall for the cohort, comparing those who achieve MRD and those who do not. | 5 years | 
| Correlative Study: Sensitivity and Specificity of Drug Resistance Assays | The investigators will also investigate sensitivity and specificity of assays of drug resistance (e.g., why this cancer eventually becomes resistant to the drugs used to treat it) | 5 years | 
| Correlative Study: Circulating Tumor DNA | The investigators will also investigate prognostic significance of circulating tumour (ct) DNA profiles | 5 years | 
| Correlative Study: Describing Myeloma Progenitor Populations | The investigators will also seek to understand how the cancer recurs and regrows, even for those who achieve an MRD state. | 5 years |