Observational Prospective Research Study In Monoclonal Gammopathies leadINg to Myeloma

PRIMARY OBJECTIVE:

I. To determine the rate of progression to multiple myeloma after 3 years of follow up.

SECONDARY OBJECTIVES:

I. To describe baseline patient characteristics and clinical variables. II. To identify molecular and genetic correlates that may predict for progression to multiple myeloma (MM).

OUTLINE:

Patients undergo collection of blood samples every 6 months for 3 years. Patients may also undergo a biopsy, x-rays, positron emission tomography (PET)/computed tomography (CT) scans, and/or magnetic resonance imaging (MRI) scans to check the status of disease at the discretion of the treating physician.

After completion of 3 years on study, patients are followed up every 6-12 months thereafter.

Inclusion criteria

• Patients with monoclonal gammopathy of unknown significance. Both criteria must be met:

• Serum monoclonal protein < 3 g/dL or urinary monoclonal protein < 500 mg per 24 hours and clonal bone marrow plasma cells < 10%
• Absence of myeloma defining events or amyloidosis
• Patients with smoldering multiple myeloma. Both criteria must be met:

• Serum monoclonal protein >= 3 g/dL or urinary monoclonal protein >= 500 mg per 24 hours and/or clonal bone marrow plasma cells 10-60%
• Absence of myeloma defining events or amyloidosis

Exclusion criteria

• Evidence of myeloma defining events or biomarkers of malignancy due to underlying plasma cell proliferative disorder meeting at least one of the following

• Hypercalcemia: serum calcium > 0.25 mmol/L (> 1 mg/dL) higher than the upper limit of normal or > 2.75 mmol/L (> 11 mg/dL)
• Renal Insufficiency: creatinine clearance < 40 ml/min or serum creatinine > 2 mg/dL
• Anemia: hemoglobin value < 10 g/dL or 2 g/dL < normal reference
• Bone lesions: one or more osteolytic lesions on skeletal radiography, computerized tomography (CT) or 2-deoxy-2[F-18] fluoro-D-glucose positron emission tomography CT (PET-CT)
• Clonal bone marrow plasma cell percentage >= 60%
• Involved:uninvolved serum free light chain ratio >= 100 measured by Freelite assay (The Binding Site Group, Birmingham, United Kingdom [UK])
• > 1 focal lesions on magnetic resonance imaging (MRI) studies (each focal lesion must be 5 mm or more in size)
• Prior or concurrent systemic treatment for asymptomatic monoclonal gammopathies

• Bisphosphonates are permitted
• Radiotherapy is not permitted
• Prior treatment with chemotherapy or investigational agents for asymptomatic gammopathies is not permitted
• Plasma cell leukemia
• Uncontrolled intercurrent illness including but not limited to active infection or psychiatric illness/social situations that would compromise compliance with study requirements