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.

• 5-Carbon C 13-labeled Glutamine (Other), also known as 5-13C-Glutamine, [5-13C]-glutamine, GLUTAMINE 5-C-13: Given IV
• Biospecimen Collection (Procedure), also known as Biological Sample Collection, Biospecimen Collected, Specimen Collection: Undergo collection of blood
• Biospecimen Collection (Procedure), also known as Biological Sample Collection, Biospecimen Collected, Specimen Collection: Undergo collection of bone marrow aspirate samples
• Uniformly-labeled [13C]glucose (Other), also known as [U-13C] Glucose, U-13C-Glucose: Given IV

Primary outcomes

• 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 [Up to 1 day]: Will compare the glutamine anaplerosis activity in bone marrow clonal plasma cells between patients with MGUS and multiple myeloma.

Secondary outcomes

• Percent enrichment of 13-Carbon in the TCA cycle intermediates within bone marrow plasma from patients with MGUS and multiple myeloma [Up to 1 day]: 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 [Up to 1 day]: Will compare the peripheral blood enrichment of 13-carbon in the TCA cycle intermediates from patients with MGUS and multiple myeloma.

Sex: Female, ages: 18 Years to any

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

• Results publication: 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. PMID 33308307

• Wilson I Gonsalves, M.D., Principal investigator, Mayo Clinic in Rochester

NIH grants: K23CA218742