Dysregulation of Glutamine Activity in the Pathogenesis of Multiple Myeloma

This clinical trial studies the utilization of glutamine by the bone marrow plasma cells from patients with monoclonal gammopathy of undetermined significance (MGUS) compared to multiple myeloma (MM). Results from this study may identify metabolic differences between pre-malignant and malignant clonal plasma cells in MGUS and MM, respectively. It may also allow researchers better determine the transition from MGUS to MM for the development of potential early diagnostic purposes of preventative strategies.

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.

EX-VIVO: After an overnight fast of 6 hours, patients undergo collection of bone marrow aspirate samples.

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

Percent enrichment of 13-Carbon in the tricarboxylic acid (TCA) cycle intermediates within bone marrow plasma cells from patients with monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma

Will compare the glutamine anaplerosis activity in bone marrow clonal plasma cells between patients with MGUS and multiple myeloma.

Percent enrichment of 13-Carbon in the TCA cycle intermediates within bone marrow plasma from patients with MGUS and multiple myeloma

Will compare the glutamine anaplerosis activity in the plasma cells by assessing the bone marrow plasma between patients with MGUS and multiple myeloma.

Percent enrichment of 13-Carbon in the TCA cycle intermediates within the peripheral blood plasma from patients with MGUS and multiple myeloma

Will compare the peripheral blood enrichment of 13-carbon in the TCA cycle intermediates from patients with MGUS and multiple myeloma.

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

Gonsalves WI, Jang JS, Jessen E, Hitosugi T, Evans LA, Jevremovic D, Pettersson XM, Bush AG, Gransee J, Anderson EI, Kumar SK, Nair KS. In vivo assessment of glutamine anaplerosis into the TCA cycle in human pre-malignant and malignant clonal plasma cells. Cancer Metab. 2020 Dec 11;8(1):29. doi: 10.1186/s40170-020-00235-4.