S1211 Bortezomib, Dexamethasone, and Lenalidomide With or Without Elotuzumab in Treating Patients With Newly Diagnosed High-Risk Multiple Myeloma

Inclusion Criteria

• Patients must have newly diagnosed active multiple myeloma (MM)
• For the Phase II portion only, patients must have high-risk MM based on one or more of the following criteria at the time of initial diagnosis (prior to any chemotherapy):
• Poor-risk genomic signature according to the University of Arkansas 70-gene model (available clinically as myeloma prognostic risk score [MyPRS] score, Signal Genetics, Inc) AND/OR
• Translocation (14;16), and/or translocation (14;20), and/or deletion (17p) by fluorescence in-situ hybridization (FISH) or cytogenetics AND/OR
• Primary plasma cell leukemia (defined by either >= 2,000 plasma cells/mL of peripheral blood, or 20% on a manual differential count) AND/OR
• Serum lactate dehydrogenase (LDH) >= 2 x institutional upper limit of normal (IULN) AND/OR
• 1q21 amplification by FISH analysis AND/OR
• High risk by the SKY92 signature
• Patients with non-secretory MM or known amyloidosis are not eligible
• Patients must have measurable disease within 28 days prior to registration (or prior to initiation of first induction course for patients with prior therapy)
• Patients on the Phase I portion may not have received ANY prior chemotherapy; patients on the Phase II portion may have received one prior cycle of any non-investigational chemotherapy; prior chemotherapy must have been completed within 56 days prior to registration and all toxicities must have resolved to = = 1,000 cells/mm^3 without growth factor support
• Platelet count >= 70, 000 cells/mm^3 for patients who have bone marrow plasmacytosis = 50,000 cells/mm^3 for patients who have bone marrow plasmacytosis of >= 50%
• Total bilirubin = = 30 mL/min, measured by a 24-hour urine collection or estimated by the Cockcroft and Gault formula within 14 days prior to registration
• Patients must not have active involvement of the central nervous system (CNS) with MM (by clinical evaluation); patients with documentation of, or clinical signs or symptoms consistent with, CNS involvement of MM must have a lumbar puncture that is negative for CNS involvement of MM; the lumbar puncture must be completed within 14 days prior to registration; patients with no previous history of documented CNS involvement and with no clinical signs or symptoms consistent with CNS involvement are not required to have completed a lumbar puncture prior to registration; note that monitoring of CNS involvement and treatment with intrathecal therapy is recommended during protocol treatment
• Patients who are known to be human immunodeficiency virus positive (HIV+) are eligible providing they meet all of the following additional criteria within 28 days prior to registration:
• Cluster of differentiation (CD)4 cells >= 500/mm^3
• Viral load of = grade 3 cardiac arrhythmias, uncontrolled hypertension, or uncontrolled diabetes mellitus; patients must have undergone an electrocardiogram (EKG) within 28 days prior to registration
• Uncontrolled diabetes: a glycated hemoglobin (Hg A1C) > 7% within 14 days prior to registration; the same criterion will be used in patients with confirmed diagnosis of diabetes mellitus who have been on a stable dietary or therapeutic regimen for this condition in the last three months
• Uncontrolled blood pressure and hypertension: systolic blood pressure (SBP) > 140 mm Hg or diastolic blood pressure (DBP) > 90 mm Hg within 14 days prior to registration; patients are permitted to be receiving multiple anti-hypertensive medications (unless otherwise indicated in the study); all blood pressure measurements within the 14 days prior to registration and on day 1 of cycle 1 must be SBP =< 140 and DBP =< 90; an exception can be made by a healthcare provider for a patient with a single blood pressure elevation who upon rechecking has a normal blood pressure
• Patients must have history and physical examination within 28 days prior to registration
• Patients must not have any psychiatric illness that could potentially interfere with