Study to Compare VMP With HDM Followed by VRD Consolidation and Lenalidomide Maintenance in Patients With Newly Diagnosed Multiple Myeloma

Prior treatment

• Previous chemotherapy or radiotherapy except local radiotherapy in case of local myeloma progression or corticosteroids maximum 5 days for symptom control;
• Patients who are not willing or capable to use adequate contraception during the therapy (all men, all pre-menopausal women);
• Allogeneic Stem Cell Transplantation (Allo SCT) planned;

Other illness

• Severe cardiac dysfunction (NYHA classification II-IV);
• Patients known to be HIV-positive;
• Patients with active, uncontrolled infections;
• 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;
• Severe pulmonary, neurologic, or psychiatric disease;
• Progressive disease.'
  • Exclusion for randomisation 2:
• Progressive disease;

Lab values

• Patients with GFR \<15 ml/min,

Other

• Known intolerance of Boron;
• Systemic AL amyloidosis;
• Primary Plasmacell Leukemia;
• Non-secretory MM;
• Significant hepatic dysfunction, unless related to myeloma;
• Patients with neuropathy, CTC grade 2 or higher;
• Lactating women.
  • Exclusion for randomisation 1:
• CTCAE grade 3-4 polyneuropathy during Bortezomib treatment;
• Neuropathy, except CTCAE grade 1;
• CTCAE grade 3-4 polyneuropathy during Bortezomib treatment.

• 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 M-protein\> 10 g/l or urine M-protein \> 200 mg/24 hours), 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);
• Negative pregnancy test at inclusion if applicable;
• Written informed consent.
  • Inclusion for randomisation 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 106 CD34+ cells/kg (or according to national guidelines).
  • Inclusion for randomisation 2:
• Bilirubin and transaminases \< 2.5 times the upper limit of normal values;
• ANC \>= 0.5 x 109/l and platelets \> 20 x 10\^9/l;
• Patient is able to adhere to the requirements of the Lenalidomide Pregnancy Prevention Risk Management Plan.