Immune Profiling in Patients with High-Risk Smoldering Myeloma

Single-cell RNA-sequencing identifies immune biomarkers of response to immunotherapy in patients with high-risk Smoldering Multiple Myeloma (SMM). We conducted a Phase II trial of the immunotherapeutic anti-SLAMF7 antibody, Elotuzumab, in combination with Lenalidomide and Dexamethasone (E-PRISM study), to determine the utility and safety of early immunotherapy in patients with high-risk SMM and develop biomarkers for optimal patient selection and monitoring of response to treatment.There is an overlap in subjects between this study and dbGaP accession phs001323. ]]>
Inclusion Criteria: Age ≥ 18 yearsMust have Smoldering Multiple Myeloma (SMM) with high-risk markers based on the Mayo or the Spanish criteria, including the new criteria for SMM as described below:Monoclonal protein in the serum of ≥ 3gm/dL and >10% plasma cells in the bone marrow with a free light chain ratio outside the range of 0.125 to 8 orRatio of abnormal to normal bone marrow plasma cells ≥ 95% or at least one immunoglobulin level lower than the normal rangeNo evidence of CRAB criteria or new criteria of overt multiple myeloma (MM) which includes the following:Increased calcium levels (corrected serum calcium >0.25 mmol/L (>1mg/dL) above the upper limit of normal or >2.75 mmol/L (>11mg/dL))Renal insufficiency (attributable to myeloma)Anemia (Hgb 2g/dL below the lower limit of normal or <10g/dL)Bone lesions (lytic lesions or generalized osteoporosis with compression fractures)No evidence of the following new criteria for active MM, including Bone marrow plasma cells ≥60%, Serum involved/uninvolved FLC ratio ≥100, and MRI with more than one focal lesion (>5mm)ECOG Performance Status (PS) 0, 1, or 2The following laboratory values obtained 21 days prior to registration:ANC ≥ 1000/uLPLT ≥ 50,000/uLTotal bilirubin ≤ 2.0 mg/dL (If total is elevated check direct and if normal patient is eligible)AST 3 x institutional upper limit of normal (ULN)ALT 3 x institutional upper limit of normal (ULN)Estimated creatinine clearance ≥ 60mL/min or a creatinine 2.2 mg/dLExclusion Criteria:Symptomatic Multiple Myeloma (SMM) or any evidence of CRAB criteria. Prior therapy for active Myeloma is also an exclusion criterion. Prior therapy for smoldering myeloma is not an exclusion criterion. Concurrent therapy with bisphosphonates is not an exclusion criterion.Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational. Prior therapy with bisphosphonate is allowed. Prior radiation therapy to a solitary plasmacytoma is allowed. Prior clinical trials for SMM or monoclonal gammopathy of undetermined significance (MGUS) are allowed as long as the last therapy was at least 2 months prior and there was no improvement in M spike.]]>