Non-invasive Diagnostics and Monitoring of MRD and Clonal Evolution in Waldenström's Macroglobulinemia and in IgM-MGUS

Study Overview
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Brief Summary
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Multicenter retrospective and prospective observational study including patients with WM or IgM-MGUS evaluated at the time of diagnosis and during the disease course using highly sensitive techniques.

Detailed Description
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Multicenter retrospective and prospective observational study including patients with WM or IgM-MGUS evaluated at the time of diagnosis and during the disease course using highly sensitive techniques such as flow cytometry, real time quantitative PCR (RT-qPCR), digital droplet PCR (dd-PCR) and NGS, in order to: evaluate the mutational status on genomic DNA or cell-free DNA and compare the results to assess the most reliable source for mutation studies; perform and compare molecular and flow cytometry analyses on bone marrow, peripheral blood (both analyses), plasma and urine samples (only molecular analysis) to assess the best source for diagnosis and MRD monitoring.

Official Title
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Non-invasive Diagnostics and Monitoring of Minimal Residual Disease and Clonal Evolution in Waldenström's Macroglobulinemia and in IgM Monoclonal Gammopathy of Undetermined Significance

Conditions
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Waldenstrom Macroglobulinemia

Intervention / Treatment
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* Other: MRD and clonal evolution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of IgM monoclonal gammopathy of undetermined significance (Ig-MGUS) or Waldenström's Macroglobulinemia (WM) according to criteria established at the second International Workshop on Waldenström's Macroglobulinemia [1] Age ≥ 18 years Previously untreated patients (only for the prospective cohort) Symptomatic or asymptomatic disease Subject understands and voluntarily signs an informed consent form approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB) Exclusion Criteria: Active HBV, HCV or HIV infection (antiHBc+ patients with undetectable HBV-DNA are eligible to the study)

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 |
| --- | --- |
| Patient enrolled<br>Part of the patients will be retrospectively enrolled (learning sample) and part prospectively (validation sample) | Other: MRD and clonal evolution<br>* Patient evaluation at the time of diagnosis and during the disease course using highly sensitive techniques<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of mutation | To demonstrate that the rate of mutations of MYD88 (L265P) and/or CXCR4 (S338X) detected in peripheral blood and/or urine show a negligible difference with the rate of mutations detected in bone marrow samples (BM, gold standard) | 22 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IgM monoclonal gammopathy, Waldenström's Macroglobulinemia, Minimal residual disease, Clonal evolution