Dysregulation of Glutamine Activity in the Pathogenesis of Multiple Myeloma

PRIMARY OBJECTIVE:

I. Compare the glutamine anaplerosis activity in bone marrow clonal plasma cells (cPCs) between patients with MGUS and MM using an in vivo and an ex vivo approach.

SECONDARY OBJECTIVES:

I. Compare the tricarboxylic acid (TCA) isotopomer enrichment in the bone marrow plasma obtained from patients with MGUS and MM with the in vivo approach.

II. Determine the peripheral blood enrichment of 13C in the TCA cycle intermediates from patients with MGUS and MM with the in vivo approach.

OUTLINE: Patients are assigned to 1 of 2 groups.

GROUP I (EX-VIVO): After an overnight fast of 6 hours, patients undergo collection of blood samples.

GROUP II (IN VIVO): After an overnight fast of 6 hours, patients receive 13-carbon labeled glutamine or 13-carbon-labeled glucose intravenously (IV) over 90 minutes. Patients also undergo collection of blood and bone marrow aspirate samples.

After completion of study, patient are followed up for 4 weeks.

Inclusion criteria

• At least 18 years of age
• International Myeloma Working Group (IMWG) criteria for the diagnosis of either MGUS or MM

Exclusion criteria

• Unable to provide consent
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) > 3
• Hemoglobin < 8 g/dL
• Women who are pregnant
• Prior history of adverse events with conscious sedation