Like a thief in the night, multiple myeloma sneaks up on people. The incurable blood cancer almost always starts as a relatively benign condition—monoclonal gammopathy of undetermined significance, or MGUS—that has no symptoms and often goes undiagnosed.
“Most people don’t know they have MGUS, and only a fraction of them will progress to multiple myeloma. But by the time the cancer is diagnosed, it has disseminated through the bone marrow,” says Angela Dispenzieri, M.D., a hematologist at the Mayo Clinic Cancer Center.
Monoclonal gammopathy has a set of “fingerprints”—the abnormal monoclonal proteins (often referred to as M proteins) that are produced by plasma cells in the bone marrow. Screening for those proteins has traditionally relied on a technology known as electrophoresis, which sorts protein molecules by size and electrical charge. That technology, largely unchanged for 50 years, has limited sensitivity.
New Tests with New Technology
Mayo Clinic Laboratories now offers enhanced testing panels for the screening and monitoring of monoclonal gammopathy. The panels employ new mass spectrometry techniques that can better identify M proteins. Test results are generally available in about a day.
“Our new assays rely on modern mass spectrometers that have higher resolutions for weighing monoclonal proteins. As a result, the tests are more sensitive at picking up the disease,” says David Murray, M.D., Ph.D., a biochemist in Mayo Clinic’s Department of Laboratory Medicine and Pathology. “Serum protein electrophoresis involves subjective reading. But mass spectrometry gives us high specificity.”
Mayo Clinic Laboratories has two new serum testing panels:
- Monoclonal Gammopathy Screen, or SMOGA, for the screening and diagnosis of monoclonal gammopathies.
- Monoclonal Gammopathy Monitoring, or MMOGA, to monitor patients with monoclonal gammopathies. This panel isn’t recommended for screening or establishing a first-time diagnosis of monoclonal gammopathy.
Free Light-Chain Analysis
SMOGA, which follows the guidelines of the International Myeloma Working Group, includes not only serum protein electrophoresis but also analysis of free light chains. That analysis can detect certain M proteins that increase the risk of abnormal-protein buildup in the body’s organs—a condition known as immunoglobulin light chain amyloidosis, or AL amyloidosis.
“Amyloidosis is a life-threatening disease. Having this biomarker for AL amyloidosis allows health care providers to think much more aggressively about amyloid when following patients with monoclonal gammopathy,” Dr. Dispenzieri says.
The development of the light-chain analysis is due to the precise measurement of protein provided by Mayo Clinic Laboratories’ high-resolution mass spectrometry. “While we were working on the new tests, we started finding M proteins that were heavier than normal,” Dr. Murray explains. “When we looked more closely at these proteins, we realized they had extra sugar groups—what we call glycosylation, which is strongly associated with AL amyloidosis.”
The precise measurement of proteins also provides enhanced monitoring of multiple myeloma treatment, especially a patient’s response to new monoclonal therapeutics. Although these therapies can be highly effective, they involve proteins similar to those made by malignant plasma cells. Distinguishing between protein related to medication and protein that is a sign of tumor action has been a challenge. Mass spectrometry allows MMOGA to make those distinctions.
“We know the molecular weights of the monoclonal therapeutics. Based on the mass of the monoclonal protein in a patient’s serum, we can say whether the protein is most likely from the drug or a marker of residual disease,” Dr. Murray says.
That information is highly beneficial for health care providers and patients. “We can tell a patient that this protein ‘fingerprint’ we see is a therapeutic monoclonal antibody. In other words, we see a fingerprint, but it’s not your M protein’s fingerprint,” Dr. Dispenzieri says.
Monitoring treatment response through blood tests also has the potential to spare patients at least some bone marrow biopsies.
“We will continue to need to test bone marrow. But if a blood test shows residual disease, there will be no point in performing a bone marrow test at that time,” Dr. Dispenzieri says. “That can save patients some pain and also save some expense.”
Mayo Clinic has a distinguished history in the diagnosis and treatment of blood disorders. MGUS was first identified at Mayo Clinic. The sensitivity and specificity of the new test panels is the latest development in this global leadership.
“Our laboratory’s ability to positively identify monoclonal proteins based on mass is unique,” Dr. Murray says. “We can obtain more positive identification of M proteins and monitor the level of those proteins to much finer levels.”