Assessing Glutamine Metabolism in MGUS and Myeloma

Multiple myeloma (MM) is always preceded by a pre-malignant asymptomatic phase, monoclonal
gammopathy of undetermined significance (MGUS). Given the incurable nature of MM it is vital
to study the development of MM from MGUS to help in identifying early diagnostic and
treatment opportunities. This project aims to determine if glutamine metabolism in plasma
cells is vital for their survival and whether it is associated with the progression of MGUS
to MM. It will involve the utilization of stable isotope resolved metabolomics methods to
evaluate the utilization of glutamine by the bone marrow plasma cells in MGUS compared to MM.
Patients with MGUS and MM will undergo bone marrow aspirations after being infused with
13-carbon labelled glutamine. The subsequent bone marrow plasma cells obtained from these
aspirates will undergo GC-MS assessments of the TCA cycle isotopomers. This will help
determine the differences in the utilization of glutamine by the bone marrow plasma cells
between MGUS and MM.

Inclusion Criteria:

- IMWG criteria for the diagnosis of either MGUS or MM5

- Presence of measurable disease defined by an M-spike of >1 g/dL and/or involved serum
free immunoglobulin light chain >10 mg/dL

For MGUS cohort only:

- At least 5 to <10% cPCs in the prior BM aspirate

- Not received any plasma cell directed therapy

For MM cohort

- At least >10% cPCs in recent BM aspirate

- Newly diagnosed MM without receiving any plasma cell directed therapy OR Relapsed MM
without having received salvage chemotherapy

Exclusion Criteria:

For both MGUS and MM cohorts

- Unable to provide consent

- ECOG PS >1

- Hemoglobin <10 g/dL

- GFR <50 ml/min

- Women who are pregnant

- Abnormal liver function tests

- Abnormal bleeding history or coagulation profile (INR >1.5)

- Prior history of adverse events with conscious sedation