Immune Profiling in Multiple Myeloma

Study Overview
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Brief Summary
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This study propose to investigate the immune repertoire of MM patients at the time of diagnosis vs. 1st vs. 2nd vs. 3rd relapse. This study will provide insights into the immune status of MM patients before and after disease transformation and help identify patients who will benefit from immunotherapy. It will also allow us to predict the efficacy of these immune-mediated strategies and their associated toxicity. By understanding the immune-microenvironment in MM patients during disease progression, the investigator will be able to better design immunotherapeutic strategies for maximal success.

Detailed Description
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Background: Immunotherapy has emerged as a new therapeutic strategy for the treatment of multiple myeloma (MM). The current immune-based strategies include the FDA-approved monoclonal antibodies elotuzumab1 and daratumumab2 targeting SLAMF7 and CD38 respectively, as well as immune approaches undergoing active clinical investigations such as bispecific T-cell engager,3 antibody-drug conjugate4 and cellular therapies like chimeric antigen receptor T cells.5-7 All of these treatment strategies are currently being tested in relapsed and refractory MM. However, MM patients, particularly those in the later stage of the disease, often have an impaired immune system.8-13 Given their curative potential, the investigator believe that immunotherapies should be used up front when the patient's immune system is still capable of mounting a normal immune response. Here the investigator propose to investigate the immune repertoire of MM patients at the time of diagnosis vs. 1st vs. 2nd vs. 3rd relapse. This study will provide insights into the immune status of MM patients before and after disease transformation and help identify patients who will benefit from immunotherapy. It will also allow us to predict the efficacy of these immune-mediated strategies and their associated toxicity. By understanding the immune-microenvironment in MM patients during disease progression, the investigator will be able to better design immunotherapeutic strategies for maximal success. Samples: Peripheral blood samples from 20 newly diagnosed, 20 relapsed and/or refractory MM patients and 10 healthy donors will be collected before therapy. An additional peripheral blood sample will be collected at relapse in patients experiencing an early relapse (within 12 months from the start of therapy). The project will include both a retrospective collection and a prospective collection of samples. Samples will be used for the current study after informed consent from the patient. The samples will be processed by Ficoll Paque gradient to isolate peripheral blood mononuclear cells (PBMCs). Peripheral blood serum will be collected as well. Enrollment time: 9 months

Official Title
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Immune Profiling in Multiple Myeloma

Conditions
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Multiple Myeloma

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: newly diagnosed MM patients or refractory MM patients or healthy donors. Esclusion criteria: not newly diagnosed MM patients or not refractory MM patients or no healthy donors.
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 |
| --- | --- | --- |
| Determine the immune transcriptome profile in the peripheral blood of MM patients at diagnosis and relapse by bulk and single cell RNAseq. | PBMC samples will be subjected to bulk and single cell RNA sequencing for a comprehensive analysis of their immune transcriptomes, including but not limited to the gene expression profiles of high-resolution subsets of B cell, T cell, NK cell and myeloid compartments. | through study completion, an average of 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the immune signatures in the peripheral blood of MM patients at diagnosis and relapse by time-of-flight mass cytometry (CyTOF). | PBMCs will be subjected to CyTOF14, 15 for detailed immune cell analysis. All the major immune cell compartments including subsets of B cells, T cells, NK cells and myeloid cells will be assessed for their potential prognostic relevance in disease progression. | through study completion, an average of 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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immune transcriptome profile, Drop-seq, immune signatures, CyTOF, cytokine profile