Inclusion Criteria:

- Age ≥ 18 years

- Confirmed diagnosis of WM (according to consensus panel / WHO criteria) with
measurable IgM paraprotein

- Previously untreated disease at any stage requiring therapy at the discretion of the
treating physician. Suggested criteria for initiating treatment include:

- haematological suppression to Hb <10 g/dl, or neutrophils <1.5x109/l or
platelets <150x109/l

- clinical evidence of hyperviscosity

- bulky lymphadenopathy and/or bulky splenomegaly

- presence of B symptoms

- No previous chemotherapy (prior plasma exchange and steroids are permissible)

- Performance status grade 0 - 2

- Life expectancy of greater than 6 months

- Informed consent

- Agreed compliance with recommended contraceptive precautions where appropriate

Exclusion Criteria:

- Lymphoplasmacytic lymphoma with no detectable serum IgM paraprotein

- Severe pre-existing neuropathy (> grade 2)

- Autoimmune cytopenias

- Evidence of active Hepatitis B or C infection (patients with evidence of past HepB
infection may be eligible - see appendix 6)

- Serological positivity for HIV

- Pregnant or lactating women

- Life expectancy severely limited by other illness

- Renal failure (creatinine clearance <30 ml/min)

- Severe impairment of liver function: alkaline phosphatase/bilirubin >2.5 times upper
limit of normal (ULN), ALT/AST >2.5 times ULN not related to lymphoma (patients with
Gilbert syndrome are eligible)

- History of allergic reaction to compounds containing boron or mannitol

- Known hypersensitivity to murine compounds.

- Diagnosed or treated for a malignancy other than WM within 5 years before day 1 of
Cycle 1 with the exception of complete resection of basal cell carcinoma, squamous
cell carcinoma of the skin or any other in situ malignancy

- Active systemic infection requiring treatment

- Concurrent treatment with another investigational agent

- Severe or life-threatening cardiac, pulmonary, neurological, psychiatric or metabolic
disease