Prospective Observational Study of Clinical and Genomic Predictors of Progression to Myeloma in Asymptomatic Monoclonal Gammopathies

Study Visits:

If participant is found to be eligible to take part in this study, every 6 months for 3
years:

- Participant will have a physical exam.

- Blood (about 1-2 tablespoons) will be collected for biomarker and routine tests and to
check the status of the disease.

- A 24 hour urine sample will be collected for routine tests.

- If the doctor thinks it is needed, participant will have a bone marrow biopsy and
aspiration, PET/CT scan, and/or MRI. This may be done, for example, if participant is
not feeling well or if there is a concern that the disease might be developing into
multiple myeloma.

One (1) time a year for 3 years, participant will have x-rays to check the status of the
disease if the doctor thinks it is needed.

Length of Study:

Participant will be taken off study if they decide to receive chemotherapy or other
treatments for the disease during the first 3 years or if they are unable to follow
directions. Participant will enter the follow-up period early if the disease gets worse.

End-of-Study Visit:

After 3 years on study, the following tests and procedures will be performed:

- Blood (about 1-2 tablespoons) will be collected for routine tests, biomarker tests, and
to check the status of the disease.

- A 24 hour urine sample will be collected for routine tests.

- Participant will have a bone marrow biopsy and aspiration to check the status of the
disease and for biomarker testing.

- Participant will have x-rays to check the status of the disease.

- If the doctor thinks it is needed, participant will have a PET/CT scan and/or MRI.

Long-Term Follow-Up:

At least 1 time every 6 to 12 months after 3 years on study:

- Blood (about 1-2 tablespoons) will be collected for routine tests and to check the
status of the disease.

- A 24 hour urine sample will be collected for routine tests.

- If the doctor thinks it is needed, participant will have a PET/CT scan, MRI, x-rays,
and/or bone marrow biopsy and aspiration.

If the disease gets worse during the 3-year study period:

- At least 1 time every 6 to 12 months, the study staff will call and ask how participant
is doing or they will be asked these questions at their regular clinic visits. These
calls should last about 15-20 minutes.

- Blood (about 2 teaspoons) will be drawn for biomarker tests.

- Participant will have a bone marrow aspiration for biomarker tests.

This is an investigational study.

Up to 200 participants will be enrolled in this study. All will take part at MD Anderson.

Inclusion Criteria:

1. Patients with monoclonal gammopathy of unknown significance age ≥ 18 years old.

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

2. Patients with smoldering multiple myeloma age ≥ 18 years old.

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:

1. 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, UK)

- >1 focal lesions on MRI studies (each focal lesion must be 5 mm or more in size)

2. 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

3. Plasma cell leukemia

4. Uncontrolled intercurrent illness including but not limited to active infection or
psychiatric illness/social situations that would compromise compliance with study
requirements