Inclusion Criteria

Inclusion criteria:

Each patient must meet all of the following inclusion criteria to be enrolled in the
study:

1. Patients aged at least 18 years with MM requiring therapy for relapsed or refractory
disease.

2. Previous VAD or VAD-like therapy (maximum 6 courses standard VAD). Subgroup
allocation is shown in 4.1

3. Measurable serum and/or urine paraprotein, or serum free light chain

4. Performance Status (PS) 0-3 (ECOG - see Appendix B)

5. Serum bilirubin values <1.5 times the upper limit of normal

6. Serum ALT/AST values <2.5 times the upper limit of normal

7. Able to give informed consent

Exclusion criteria:

Patients meeting any of the following exclusion criteria are not to be enrolled in the
study:

1. Females of child-bearing potential without a negative pregnancy test, immediately
prior to the start of PAD therapy and/or unwilling to use barrier contraceptive
precautions throughout the study or who are pregnant or breast-feeding

2. Men with partners of child bearing potential unwilling to use a medically acceptable
form of contraception

3. Patients with non-secretory MM and no measurable elevation of serum free light chain

4. Performance status 4 (ECOG)

5. Patient has a platelet count <75 x 10^9/L within 14 days before enrolment

6. Patient has an absolute neutrophil count <1.0 x 10^9/L within 14 days before
enrolment

7. Patient has a serum creatinine > 400 micromol/l at the time of enrolment

8. Patient has Grade 2 or greater than Grade 2 peripheral neuropathy or neuropathic pain
as defined by NCI Common Terminology Criteria for Adverse Events version 3.0 (CTCAE)
within 14 days before enrolment

9. Cardiac ejection fraction <40% by echocardiography or MUGA scan

10. Known HIV seropositivity (obligatory testing is not necessary)

11. Known Hepatitis B or C (obligatory testing is not necessary)

12. Patients who have received more than one autologous transplant

13. Use of any investigational drug within 4 weeks prior to enrolment or any patients
scheduled to receive any investigational drug during the course of the study

14. Previous Bortezomib therapy

15. Patients who have a medical or psychiatric condition which, in the opinion of the
investigator, contraindicates the patient's participation in this study

16. Previous or concurrent malignancies at other sites, with the exception of
appropriately treated localized epithelial skin or cervical cancer. Patients with
remote histories (>5 years) of other cured tumours may be entered

17. Plasma exchange within 21 days of enrolment