Inclusion Criteria:

A - Clinicopathological diagnosis of WM as defined by consensus panel one of the Second
International Workshop on WM49. Pathological diagnosis has to occur by the national
pathological reference center before study inclusion and randomization. The positivity for
CD20 positive can be assumed from any previous bone marrow immunohistochemistry or flow
cytometry analysis performed up to 3 months prior to enrollment. Inclusion in the protocol
will be based on morphological and immunological criteria. Immunophenotyping will be
performed in each center and saved locally. Flow cytometry of bone marrow and blood cells
will include at least one double staining and assess the expression of the following
antigens: surface immunoglobulin, CD19, CD20, CD5, CD10 and CD23. Patients are eligible if
tumor cells express the following antigens: CD19, CD20, and if they are negative for CD5,
CD10 and CD23 expressions. Patients with tumor cells positive for CD5 or CD23 and
morphologically similar to WM cells may be included after ruling out other low-grade
B-cell malignancies.

B - No prior systemic treatment for WM. Prior plasmapheresis to control hyperviscosity is
allowed and encouraged to avoid IgM flare before Rituximab application. In that case
baseline monoclonal protein levels for assessment of response will be the levels prior to
plasmapheresis, if this is the highest value prior to treatment initiation.

C - Patients must have at least one of the following critera to initiate treatment as
defined by "Consensus Panel Two" recommendations from the Second International Workshop on
Waldenström Macroglobulinemia 2.

- Recurrent fever, night sweats, weight loss, fatigue

- Hyperviscosity

- Lympadenopathy which is either symptomatic or bulky (≥5cm in maximum diameter)

- Symptomatic hepatomegaly and/or splenomegaly

- Symptomatic organomegaly and/or organ or tissue infiltration

- Peripheral neuropathy due to WM

- Symptomatic cryoglobulinemia

- Cold agglutinin anemia

- Immune hemolytic anemia and/or thrombocytopenia

- Nephropathy related to WM

- Amyloidosis related to WM

- Hemoglobin ≤10g/dL

- Platelet count <100x109/L

- Serum monoclonal protein >5g/dL even with no symptoms D - Cumulative illness rating
scale (CIRS) score less than 6 (see annex). E - World Health Organization (WHO)
performance status 0 to 2. F - Other criteria

- Age greater than 18 years

- Life expectancy >3 months.

- Baseline platelet count >= 50 x109/L (if not due to BM infiltration by the lymphoma),
absolute neutrophil count >= 0.75x109/L.

- Meet the following pretreatment laboratory criteria at the Screening visit conducted
within 28 days of study enrollment:

- ASAT (SGOT): <=3 times the upper limit of institutional laboratory normal value.

- ALAT (SGPT): <=3 times the upper limit of institutional laboratory normal value.

- Total Bilirubin: <=20 mg/L or 2 times the upper limit of institutional
laboratory normal value, unless clearly related to the disease (except if due to
Gilbert's syndrome).

- Calculated or measured creatinine clearance: >= 30 mL/minute. G - Voluntary
written informed consent before performance of any study-related procedure not
part of normal medical care, with the understanding that consent may be
withdrawn by the subject at any time without prejudice to future medical care.

Exclusion Criteria:

- Prior systemic treatment of the WM (plasmapheresis is allowed)

- Marginal zone lymphoma with bone marrow infiltration. All efforts should be made,
using cytogenetics or molecular studies in order to rule out a diagnosis of marginal
zone lymphoma

- IgM myeloma: In case of bone localization, cytogenetics should be performed to rule
out the presence of t(11;14) translocation and to check the presence of abnormalities
usually found in WM

- Patient with hypersensitivity to dexamethasone.

- Serious medical or psychiatric illness likely to interfere with participation in this
clinical study.

- Cardiac amyloidosis

- Women who are pregnant. Women who are breast-feeding and do not consent to
discontinue breast-feeding. Women of childbearing age who are not willing to use
effective anti-conceptive methods for the duration of the study and 6 months
thereafter.

- Men who do not consent not to father a child during the treatment period and six
months thereafter.

- Bacterial, viral or fungal infection (except nail bed infection). Mycobacterial
infection or any other infection in progress. Any important infection requiring
hospitalization or intravenous antibiotic therapy within the 4 weeks before
inclusion. Any important infection requiring oral antibiotic therapy within the 2
weeks before screening visit.

- Prior deep infection (abscess, osteomyelitis, septic arthritis, fasciitis) within the
year before inclusion.

- Prior severe, chronic or recurrent infection, any other underlying disorders
resulting in an increased risk of severe infection.

- HIV, HBV or HCV infection

- Other severe infection within the 3 months before the inclusion (CMV, HHV8… ).

- Active primary or secondary immunodeficiency. Past primary or secondary
immunodeficiency.

- Known diffuse infiltrative pulmonary disease

- Live attenuated immunization within the 4 weeks before inclusion.

- Previous therapy associated with lymphocyte depletion.

- Prior allergic reaction or severe anaphylactic reaction related to humanized or
murine monoclonal antibody.

- Any of the following laboratory abnormalities, if not related to lymphoma:

- Absolute neutrophils count < 0.75 x 109/L) if not result of a bone marrow
infiltration.

- Platelet count < 50 x 109/L) if not result of a bone marrow infiltration.

- Central Nervous System involvement by lymphoma

- Prior history of malignancies unless the subject has been free of the disease for ≥ 5
years. Exceptions include the following:

- Basal cell carcinoma of the skin,

- Squamous cell carcinoma of the skin,

- Carcinoma in situ of the cervix,

- Carcinoma in situ of the breast,

- Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b).

- Uncontrolled illness including, but not limited to:

- Uncontrolled diabetes mellitus

- Chronic symptomatic congestive heart failure (Class NYHA III or IV).

- Unstable angina pectoris, angioplasty, stenting, or myocardial infarction within
6 months

- Clinically significant cardiac arrhythmia that is symptomatic or requires
treatment, or asymptomatic sustained ventricular tachycardia.

- Known pericardial disease

- Subjects with ≥ Grade 2 neuropathy.

- Participation in another clinical trial within 4 weeks before randomization in this
study

- No consent for registration, storage and processing of the individual
disease-characteristics and course as well as information of the family physician
about study participation.