Current Ways to Diagnose and Monitor Myeloma

Diagnostics is a term that refers to a wide range of tests and procedures that can be done to diagnose and monitor a disease. Many different diagnostic tools are available for myeloma. These tests can be done to diagnose, evaluate treatment response, or monitor for myeloma progression. While some of these tools are invasive (meaning they require entrance into the body), many are minimally invasive or non-invasive (meaning they do not).

Current diagnosis and monitoring of myeloma are traditionally done using a combination of tests and procedures:

  • Blood tests:
    • A complete blood count (CBC) to look at the levels of specific types of blood cells, such as red and white blood cells
    • A chemistry panel, which helps evaluate your overall health and electrolytes (minerals in your body) as well as specific levels of substances important in the diagnosis of myeloma (e.g., calcium levels and creatinine to measure kidney function)
    • Serum Protein Electrophoresis (SPEP), which measures the amount of a specific myeloma protein in the blood (monoclonal proteins)
    • Beta-2 microglobulin ( β2M) is a protein found in the blood. β2M measurements are a part of a common myeloma staging system, the Revised International Staging System (R-ISS). Lower levels of β2M are associated with a better prognosis.  
  • Urine tests:
    • Urine Protein Electrophoresis (UPEP), which measures the amount of a type of protein in the urine (monoclonal proteins) made by myeloma cells.
  • Bone marrow testing to:
    •  Look at the cytogenetics (the DNA or genetic changes also called mutations) of the myeloma cells 
    • Perform immunophenotyping (looking at the type of antigens or proteins present on the surface of the myeloma cell, such as BCMA, which may be targets for myeloma treatments)
    • Fluorescence in situ hybridization (FISH) testing 
  • Imaging testing such as MRIs, CT scans, or PET Scans are also part of diagnosing and monitoring myeloma.

For more details on standard-of-care testing, please see International Myeloma Working Group (IMWG) Criteria for the Diagnosis of Multiple Myeloma. Despite the availability of multiple diagnostic tests, scientists and researchers continually work to develop new and improved diagnostics and prognostic tests for myeloma. Below are some of the newest and most promising emerging tools.

Minimal Residual Disease (MRD) Testing

Minimal residual disease (MRD) refers to the small number of myeloma cells that may survive in your body after treatment. The amount of these cells is so small that you may not show any signs or symptoms of myeloma. Also, most of the time, the number of cells is too small to be detected through standard testing. MRD tests are so sensitive that they can detect 1 myeloma cell in 1 million healthy cells. 

MRD testing is used to help know if your myeloma is in remission, if you are likely to relapse, and if you need further treatment.
Currently, the standard approach to MRD testing is to assess the number of myeloma cells present in a bone marrow sample. Broadly, the following two techniques have been used:

  • Genetic sequence analysis: Next Generation Sequencing (NGS)
  • Flow cytometry: Next Generation Flow (NGF)

Even though NGS is an FDA-approved test, it’s exact role in disease-monitoring is not yet established. The NGF method is not yet FDA-approved, so no protocols exist for standard disease-monitoring using NGF. 

The i2TEAMM, a group brought together by the IMF, is engaged with the FDA in seeking approval for MRD as an early endpoint to assess response in clinical trials. As of April 12, 2024, the the Oncologic Drug Advisory Committee (ODAC) unanimously voted in favor (12-0) of using minimal residual disease (MRD) as an early endpoint for accelerated approval in multiple myeloma clinical trials. Read the full press release here.

In clinical practice, no accepted standard of care is established. If MRD is undetected, this status is obviously excellent. Yet, more trial information is required to guide decision-making. Sustained MRD that is undetected for six months or one year is particularly promising in terms of potential long-term remissions or improved survival.

However, is it safe or recommended to stop treatment with sustained MRD? Conversely, if residual disease is detected, is new treatment required? These questions remain open. 
MRD test results must be discussed with your doctor to assess any options for changes to treatment or not. An MRD-negative status is obviously good, but an MRD-positive status may indicate a low (and potentially stable) level or residual disease. This status does not necessarily indicate need for treatment changes. 

For more information on MRD, please visit the International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma.

Mass Spectrometry Testing

Mass spectrometry is a very sensitive test for measuring the level of myeloma protein (monoclonal protein) in the blood. The high sensitivity means that previously undetected proteins can be discovered. At the point of early disease, new cases of monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma (SMM) can be diagnosed. 

During assessment of response, much deeper levels of response and much earlier indicators or response can be documented. 

Currently, mass spectrometry can be conducted at a few reference laboratories such as Mayo Clinic Medical Labs in Rochester, Minnesota. 

It is hoped that the FDA will approve mass spectrometry testing some time in 2023. If so, the approval will obviously improve broad access to the testing. 

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