Blood Test May Improve Multiple Myeloma Detection, Monitoring

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Just 5% of myeloma cases are in the first phase at diagnosis.

Just 5% of myeloma cases are in the first phase at diagnosis.

The lack of quality routine screening tests that identify patients who are likely to progress to multiple myeloma remains a problem for care providers.

Recent research seeks to overcome this problem, however. A study in The Journal of Molecular Diagnostics noted that nearly all patients who develop myeloma experience a disease called monoclonal gammopathy of undetermined significance (MGUS) prior to the development of myeloma.

The 5-year relative survival rate for the disease is 69% among patients diagnosed with stage 1 or localized disease, which compares favorably to the 45% survival rate of patients with advanced cancer. However, just 5% of myeloma cases are stage 1 at the time of diagnosis, which the study notes may be due to a shortage in quality routine screening tests that identify these patients.

The study revealed that abnormal levels of microRNAs (miRNAs) in the bone marrow of multiple myeloma patients may also be found in peripheral blood. Measuring these factors may allow researchers to track the onset of myeloma while also tracking progression from early asymptomatic stages.

While 1% of patients with MGUS go on to develop myeloma each year, 10% of patients with smoldering myeloma (SMM) advance to develop the disease.

"Currently there is no single factor that can predict patients with MGUS or SMM who are likely to progress to myeloma,” said lead investigator Katherine R. Calvo, MD, PhD, of the Hematology Section of the Department of Laboratory Medicine of the National Institutes of Health (NIH) Clinical Center. “A biomarker of disease progression in the peripheral blood could assist in the early identification of patients evolving to multiple myeloma.”

The researchers evaluated bone marrow, plasma, and serum samples from patients with myeloma, patients with MGUS, patients with SMM, and a healthy control group. After evaluating bone marrow fluid from 20 patients with myeloma, researchers identified 111 miRNAs with a 2-fold or greater difference from the levels found in 8 of the healthy control samples.

About 60% of miRNAs were down-regulated, while 38% were up-regulated. The researchers also found the unique miRNA signature that is indicative of myeloma.

The study also showed miRNA profiles indicative of myeloma in peripheral blood serum and plasma samples. An analysis of serum samples from 17 patients with MGUS, 17 with SMM, 13 with myeloma, and 12 healthy controls showed that 4 of 11 miRNAs that were decreased in the myeloma serum samples were also lower in the MGUS samples.

"This suggests that aberrant expression of these [4] miRNAs may be associated with early events in plasma cell neoplasia," Dr. Calvo said.

Furthermore, 8 of 11 miRNAs were reduced in SMM plasma samples, while 3 were significantly decreased in just the myeloma samples. This indicates down-regulation of this group of miRNAs could be associated with the progression from precursor disease to myeloma, the study noted.

"Our findings suggest that the antiproliferative and proapoptotic miRNAs, such as the let-7 family members, are down-regulated in multiple myeloma's microenvironment,” Dr. Calvo said. “These findings suggest that measuring expression of miRNAs associated with myeloma progression in the peripheral blood may hold promise for predicting disease progression in MGUS and SMM.”

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