A Phase III Trial on the Effect of Elotuzumab in VRD Induction /Consolidation and Lenalidomide Maintenance in Patients With Newly Diagnosed Myeloma

Inclusion Criteria:

* Patients meeting all of the following criteria will be considered for admission to the trial:
* Confirmed diagnosis of untreated multiple myeloma requiring systemic therapy (diagnostic criteria (IMWG updated criteria (2014) )
* Measurable disease, defined as any quantifiable monoclonal protein value, defined by at least one of the following three measurements:

  * Serum M-protein ≥ 10g/l (for IgA ≥ 5g/l)
  * Urine light-chain (M-protein) of ≥ 200 mg/24 hours
  * Serum FLC assay: involved FLC level ≥ 10 mg/dl provided sFLC ratio is abnormal
* Age 18 - 70 years inclusive
* WHO performance status 0-3 (WHO=3 is allowed only if caused by MM and not by co-morbid conditions)
* Negative pregnancy test at inclusion (women of childbearing potential)
* For all men and women of childbearing potential: patients must be willing and capable to use adequate contraception during the complete therapy. Patients must agree on the requirements regarding the lenalidomide pregnancy prevention programme described in chapter 6.
* All patients must

  * agree to abstain from donating blood while taking lenalidomide and for 28 days following discontinuation of lenalidomide therapy
  * agree not to share study drug lenalidomide with another person and to return all unused study drug to the investigator or pharmacist
* Ability of patient to understand character and individual consequences of the clinical trial
* Written informed consent (must be available before enrollment in the trial)

Exclusion Criteria:

* Patients presenting with any of the following criteria will not be included in the trial:
* Patient has known hypersensitivity to any drugs given in the protocol, notably bortezomib, lenalidomide, dexamethasone and elotuzumab or to any of the constituent compounds (incl. boron and mannitol).
* Systemic AL amyloidosis (except for AL amyloidosis of the skin or the bone marrow)
* Previous chemotherapy or radiotherapy during the past 5 years except local radiotherapy in case of local myeloma progression.
* Severe cardiac dysfunction (NYHA classification III-IV)
* Significant hepatic dysfunction (serum bilirubin ≥ 1,8mg/dl and/or ASAT and/or ALAT ≥ 2.5 times normal level), unless related to myeloma.
* Patients with renal insufficiency requiring hemodialysis
* HIV positivity
* Patients with active or history of hepatitis B or C
* Patients with active, uncontrolled infections
* Patients with peripheral neuropathy or neuropathic pain, CTC grade 2 or higher (as defined by the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0)
* Patients with a history of active malignancy during the past 5 years with the exception of basal cell carcinoma of the skin or stage 0 cervical carcinoma treated with curative intent
* Patients with acute diffuse infiltrative pulmonary and/or pericardial disease
* Autoimmune hemolytic anemia with positive Coombs test or immune thrombocytopenia
* Platelet count \< 75 x 109/l, or, dependent on bone marrow infiltration by plasma cells, platelet count \< 30 x 109/l (patients with platelet count \< 75 x 109/l, but \> 30 x 109/l may be eligible if percentage of plasma cells in bone marrow is ≥ 50%), (transfusion support within 14 days before the test is not allowed)
* Haemoglobin ≤ 8.0 g/dl, unless related to myeloma
* Absolute neutrophil count (ANC) \< 1.0 x 10\^9/l (the use of colony stimulating factors within 14 days before the test is not allowed), unless related to myeloma
* Pregnancy and lactation
* Participation in other clinical trials. This does not include long-term follow-up periods without active drug treatment of previous studies during the last 6 months.

No patients will be allowed to enrol in this trial more than once.