Myélome

• Histologically confirmed diagnosis, measurable disease and evidence of disease progression of MM, as described below.
• Symptomatic MM, based on IMWG guidelines. Patients must have measurable disease as defined by at least one of the following:
• Serum M-protein ≥ 0.5 g/dL by serum electrophoresis (SPEP) or, for IgA myeloma, by quantitative IgA
• Urinary M-protein excretion at least 200 mg/24 hours
• Serum FLC ≥ 100 mg/L, provided that FLC ratio is abnormal
• If serum protein electrophoresis is felt to be unreliable for routine M-protein measurement, then quantitative Ig levels by nephelometry or turbidometry are acceptable.
• Any non-hematological toxicities (except for peripheral neuropathy as described in exclusion criterion #22) that patients experienced from treatments in previous clinical studies must have resolved to ≤ Grade 2 by Cycle 1 Day 1.
• Adequate hepatic function within 21 days prior to C1 D1:
• Adequate renal function within 21 days prior to C1 D1:
• Adequate hematopoietic function within 21 days prior to C1 D1:

SdP (Arm 1) Only:

Relapsed and refractory MM with:

• Documented evidence of PD after achieving at least SD for ≥ 1 cycle during a previous MM regimen (i.e., relapsed MM)
• ≤ 25% response (i.e., patients never achieved ≥ MR) or PD during or within 60 days from the end of the most recent MM regimen (i.e., refractory MM)
• Previously undergone ≥ 2 cycles of lenalidomide and a proteasome inhibitor (in separate therapeutic regimens [not for maintenance] or in combination)

SdB (Arm 2) Only:

Relapsed or refractory MM with:

• Documented evidence of relapse after ≥ 1 previous line of therapy
• Not refractory to bortezomib in their most recent line of therapy 9. SdL (Arm 3) Only:
• Patients who received ≥ 1 prior therapeutic regimen (prior lenalidomide is allowed as long as patient was not refractory to prior lenalidomide)

• Smoldering MM.
• MM that does not express M-protein or FLC (i.e., non-secretory MM is excluded), and quantitative immunoglobulin levels cannot be used instead
• Documented active systemic amyloid light chain amyloidosis
• Active MM involving the central nervous system (CNS)
• Active plasma cell leukemia
• Blood (or blood product) transfusions and blood growth factors within 7 days of C1 D1 only for patients enrolling into the Expansion Phase
• Radiation, chemotherapy, or immunotherapy or any other anticancer therapy ≤ 2 weeks prior to C1 D1, and radio-immunotherapy within 6 weeks prior to C1 D1. Patients on long-term glucocorticoids during Screening, including use for spinal cord compression, do not require a washout period. Prior radiation is permitted for treatment of fractures or to prevent fractures as well as for pain management
• Treatment with an investigational anti-cancer therapy within 3 weeks prior to C1 D1
• Prior autologous stem cell transplantation < 1 month, or allogeneic stem cell transplantation < 3 months prior to C1 D1
• Active graft versus host disease after allogeneic stem cell transplantation
• A life expectancy of < 3 months
• Major surgery within 4 weeks prior to C1 D1

• Active, unstable cardiovascular function: