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.

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.

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)

The study population will include either IgM-MGUS, asymptomatic WM or symptomatic WM patients requiring treatment. Patients in need of therapy will be treated according to recently published guidelines [49]. Patients treated with new agents, including the BTK inhibitor Ibrutinib, will be included. Patient enrolled retrospectively will constitute the learning cohort of the study, while those enrolled prospectively will constitute the validation cohort).