CURATE.AI Optimized Modulation for Multiple Myeloma

Inclusion Criteria:

1. Multiple myeloma diagnosed according to standard criteria, without prior anti-myelomatreatment at study entry. Both transplant eligible and ineligible patients may beincluded.
2. Patients must have evaluable multiple myeloma with at least one of the following (within 21 days of starting treatment)
3. Serum M-protein ≥ 0.5g/dL, or
4. In subjects without detectable serum M-protein, Urine M-protein ≥ 200mg/24 hour,or serum free light chai (sFLC) > 100mg/L (involved light chain) and an abnormalkappa/Lambda ratio
5. Males and females ≥ 18 years of age or > country's legal age for adult consent
6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2
7. Patients must meet the following clinical laboratory criteria with 21 days of startingtreatment:
8. Absolute neutrophil count (ANC) ≥ 1,000/mm3 and platelet ≥ 50,000/mm3 (≥ 30,000/mm3 if myeloma involvement in the bone marrow is >50%)
9. Total bilirubin ≤ 1.5 x the upper limit of the normal range (ULN). Alanineaminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN.
10. Calculated creatinine clearance ≥ 30mL/min or creatinine < 3mg/dL.
11. Written informed consent in accordance with federal, local and institutionalguidelines

Exclusion Criteria:

1. Female patients who are lactating or pregnant
2. Multiple Myeloma of IgM subtype
3. Glucocorticoid therapy (prednisolone > 30mg/day or equivalent) within 14 days prior toinformed consent obtained
4. POEMS syndrome
5. Plasma cell leukaemia or circulating plasma cells ≥ 2 x 109/L
6. Waldenstrom's Macroglobulinaemia
7. Patients with known amyloidosis
8. Chemotherapy with approved or investigation anticancer therapeutics within 21 daysprior to starting bortezomib treatment
9. Focal radiation therapy within 7 days prior to start of treatment. Radiation therapyto an extended field involving a significant volume of bone marrow within 21 daysprior to start of treatment
10. Immunotherapy (excluding steroids) 21 days prior to start of treatment
11. Major surgery (excluding kyphoplasty) within 28 days prior to start of treatment
12. Active congestive heart failure (New York Heart Association [NYHA] Class III or IV),symptomatic ischaemia, or conduction abnormalities uncontrolled by conventionalintervention. Myocardial infarction within 4 months prior to informed consent obtained
13. Known HIV seropositive, hepatitis C infection, and/or hepatitis B (except for patientswith hepatitis B surface antigen or core antibody receiving and responding toantiviral therapy directed at hepatitis B: these patients are allowed)
14. Patients with known cirrhosis
15. Second malignancy within the past 3 years except:
16. Adequately treated basal cell or squamous cell skin cancer
17. Carcinoma in situ of the cervix
18. Breast carcinoma in situ with full surgical resection
19. Patients with myelodysplastic syndrome
20. Patients with steroid, cyclophosphamide, bortezomib, lenalidomide or thalidomidehypersensitivity
21. Patients with a calculated creatinine clearance less than 30ml/min by the CockroftGalt method.
22. Prior treatment with Bortezomib
23. Contraindication to any of the required concomitant drugs or supportive treatments
24. Any clinically significant medical disease or psychiatric condition that, in theinvestigator's opinion, may interfere with protocol