Treatment with carfilzomib, lenalidomide and dexamethasone versus lenalidomide and dexamethasone in patients with high-risk smoldering Multiple Myeloma

Prior treatment

• Significant cardiovascular disease with NYHA grade III or IV symptoms, or hypertrophic cardiomegaly, or restrictive cardiomegaly, or myocardial infarction within 3 months prior to enrollment, or unstable angina, or unstable arrhythmia
• Major surgery within 1 month prior to enrollment
• Patients who are receiving any other investigational agents.
• Concurrent systemic treatment or prior therapy within 4 weeks for SMM
• Contraindication to any concomitant medication, including antivirals, anticoagulation prophylaxis, tumor lysis prophylaxis, or hydration given prior to therapy

Other illness

• Active hepatitis B or C infection
• Known or suspected HIV infection
• Incidence of gastrointestinal disease that would prevent absorption
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection.
• History of other malignancy (apart from basal cell carcinoma of the skin, or in situ cervix carcinoma) except if the patient has been free of symptoms and without active therapy during at least 5 years
• Pre-existing pulmonary, cardiac or renal impairement that prevents hydration measures
• Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule
• History of allergic reactions attributed to immunomodulatory agents and proteasome inhibitors.
• Uncontrolled hypertension or diabetes

Other

• Patients with symptomatic multiple myeloma (i.e. having myeloma defining events)
• Patients with gastric or duodenal ulcers
• Significant neuropathy ≥Grade 3 or grade 2 with pain within 14 days of enrollment
• Amyloid Light-chain (AL) amyloidosis
• Hypersensitive reaction to active substances or any excipients of the IMPs
• Pregnant or lactating females.

• Patients must have histologically or cytologically confirmed Smoldering Multiple Myeloma based on the 2014 International Myeloma Working Group Criteria: Serum M-protein ≥3 g/dl or urinary monoclonal protein >500 mg per 24 hours and/or Absence of CRAB symptoms and myeloma defining events
• Written informed consent
• Calculated Creatinine Clearance ≥ 50 ml/min
• Patient is capable of giving informed consent
• Patients must have high risk Smoldering Multiple Myeloma based on the Mayo Clinic and/or the PETHEMA criteria
• Measurable disease
• Age >18 years
• WHO/ECOG performance status <=2
• Patients must have normal organ and marrow function
• Patients must be willing and capable to use adequate contraception during and after the therapy (all men, all premenopausal women) Patients must be able to adhere to the requirements of the Lenalidomide Pregnancy Prevention Plan
• Females of childbearing potential must have a negative serum or urine pregnancy test within 10 - 14 days prior to entry and again within 24 hours of starting lenalidomide treatment