Inclusion criteria
- Patients with a confirmed diagnosis of symptomatic multiple myeloma stage I to III according to the International Staging System ISS (see appendix A), i.e. at least one of the CRAB criteria should be present;
- Measurable disease as defined by the presence of M-protein in serum or urine (serum Mprotein > 10 g/l or urine M-protein > 200 mg/24 hours or abnormal FLC ratio with involved free light chain (FLC) > 100 mg/l) or proven plasmacytoma by biopsy;), or abnormal free light chain ratio;
- Age 18-65 years inclusive;
- WHO performance status 0-3 (WHO=3 is allowed only when caused by MM and not by comorbid conditions) (see appendix D);
- Negative pregnancy test at inclusion if applicable;
- Written informed consent.
Randomization 1
- WHO performance 0-2;
- Bilirubin and transaminases < 2.5 times the upper limit of normal values;
- A suitable stem cell graft containing at least 4 x 10^6 CD34+ cells/kg (or according to national guidelines).
Randomization 2
- Bilirubin and transaminases < 2.5 times the upper limit of normal values;
- ANC >= 0.5 x 10^9/l and platelets > 20 x 10^9/l;
- Patient is able to adhere to the requirements of the Lenalidomide Pregnancy Prevention Risk Management Plan.
Exclusion criteria
- Known intolerance of Boron;
- Systemic AL amyloidosis;
- Primary Plasmacell Leukemia;
- Non-secretory MM;
- Previous chemotherapy or radiotherapy except local radiotherapy in case of local myeloma progression or corticosteroids maximum 5 days for symptom control;
- Severe cardiac dysfunction (NYHA classification II-IV, see appendix E);
- Significant hepatic dysfunction (serum bilirubin >= 30 mmol/l or transaminases >= 2.5 times normal level), unless related to myeloma;
- Patients with GFR <15 ml/min,
- Patients known to be HIV-positive;
- Patients with active, uncontrolled infections;
- Patients with neuropathy, CTC grade 2 or higher;
- Patients with a history of active malignancy during the past 5 years with the exception of basal carcinoma of the skin or stage 0 cervical carcinoma;
- Patients who are not willing or capable to use adequate contraception during the therapy (all men, all pre-menopausal women);
- Lactating women.
Randomization 1
- Severe pulmonary, neurologic, or psychiatric disease;
- CTCAE grade 3-4 polyneuropathy during Bortezomib treatment;
- Allogeneic Stem Cell Transplantation (Allo SCT) planned;
- Progressive disease.
Randomization 2
- Progressive disease;
- Neuropathy, except CTCAE grade 1;
- CTCAE grade 3-4 polyneuropathy during Bortezomib treatment.
