Hypothesis; That inhibition of plasma Blys by the monoclonal antibody Belimumab will reduce both the survival of the lymphoplasmacytoid cells of Waldenstrom Macroglobulinaemia (WM), and their production of monoclonal IgM, resulting in a reduction of IgM paraprotein.

Inclusion Criteria:

• At least 18 years of age.

• Diagnosis of WM histologically confirmed on bone marrow biopsy.

• Detectable IgM paraprotein >5 g/L

• Less than 3 lines of prior therapy for WM

• Full blood count within 4 weeks prior to screening shows ANC >1.0 x109/l AND platelet count >50 x109/l

• Therapy indicated due to development of one or more of the following:

  1. symptomatic anaemia
  2. hyperviscosity symptoms
  3. rapidly rising paraprotein of >25% or >5g/l over 3 months
  4. splenomegaly
  5. bulky lymphadenopathy
  6. B symptoms or paraneoplastic phenomena, which, in the opinion of the investigator are the result of progressive WM.

• Life expectancy >12 months

• ECOG < 3

• Able to provide informed consent

• Ability to understand the requirements of the study, provide written informed consent, including consent for the use and disclosure of research-related health information, and comply with the protocol procedures, including required study visits.

• Subjects of child bearing potential must agree to use effective contraception throughout the study and for 3 months after the last dose of belimumab

Exclusion Criteria:

• Prior therapy with belimumab.
• Pregnant or breast feeding
• Chemotherapy, immunotherapy or biological therapy within 4 weeks of enrolment. Therapeutic plasma exchange can continue- see section 3.1.4.
• Creatinine clearance (calculated by Cockcroft-Gault) < 60ml/min
• Bilirubin >2x ULN, ALT >2x ULN.
• History of an allergic or anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies, a history of severe allergic reaction to drugs, food, or insects requiring medical intervention, or a history of hypersensitive triad (having all 3 features of allergic rhinitis with nasal polyps, asthma, and aspirin sensitivity).
• Prior opportunistic infection including tuberculosis or atypical mycobacterial infection, multi-dermatome Herpes Zoster or Pneumocystis pneumonia or invasive fungal infection (not including oral or vaginal candidiasis or superficial dermatophytes) .
• Active infection with hepatitis B, hepatitis C or HIV or historically positive test or test positive at screening for HIV antibody, hepatitis B surface antigen, or hepatitis C antibody.
• History of organ transplant (eg, heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant.
• Planned surgical procedure during the treatment period of this study or a history of any other medical disease (eg, cardiopulmonary), laboratory abnormality, or condition that, in the opinion of the principal investigator, makes the subject unsuitable for the study.
• Hospitalization for treatment of infection within 60 days of Day 1.
• Use of parenteral (IV or IM) antibiotics (antibacterials, antivirals, anti-fungals, or anti parasitic agents) within 60 days of Day 1.
• Current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence within 364 days prior to Day 1.