Efficacy of Bortezomib (Velcade(R)) in Patients With Advanced Waldenström Macroglobulinemia

Inclusion Criteria:

● Established diagnosis of Waldenström macroglobulinemia (the 2nd Workshop on Waldenstrom's macroglobulinemia)

Patient must have had 1 (or 2) lines of chemotherapy containing alkylating agent and/or Fludarabine :and /or monoclonal antibody and must have :

* Life expectancy \> 3 months
* Age \> 18 years
* ECOG performance status 0-1-2
* ANC \> 1 x 109/L
* Creatinine clearance, calculated according to the formula of cockcroft and Gault \> 40 ml/min
* Total bilirubin \< 2x ULN
* ASAT, ALAT \< 2x ULN
* A negative serum pregnancy test one week prior to treatment must be available both for pre-menopausal women and for women who are \< 2 years after the onset of menopause
* Adequate contraceptive methods for males and pre-menopausal females for 6 months after treatment discontinuation.
* Written informed consent
* Platelets\> 100X 109

Exclusion Criteria:

* Active secondary malignancy or chemotherapy/radiotherapy for any neoplastic disease other than Waldenström macroglobulinemia prior to the study
* Medical condition requiring the long-term (estimated to be more than one month) use of oral corticosteroids
* Patients with active bacterial, viral or fungal infection
* Known infection with HIV, Hepatitis B (except post vaccinal profile) or C
* Treatment with any, other investigational agent or participating in another trial within 30 days prior to entering this study
* Lactation/pregnancy
* Concurrent severe diseases which exclude the administration of therapy heart insufficiency NYHA grade III/IV, LEVF \< 50% and or RF \< 30%, myocardial infarction within the past 6 months prior to study
* Severe pulmonary or heart problems (acute diffuse pulmonary and pericardial disease)
* Severe chronic obstructive lung disease with hypoxemia
* Severe diabetes mellitus
* Hypertension difficult to control
* Impaired renal function with creatinine clearance \< 40 ml/min according to the formula of Cockcroft and Gault
* Cerebral dysfunction
* Richter's syndrome
* Neuropathy\> grade 1
* Positive Beta HCG
* Severe Hepato cellular alteration