A type of test called the free light chain assay can frequently detect oligo­secretory disease in multiple myeloma patients. The findings, discussed in a letter to the editor of The New England Journal of Medicine, also indicate that oligosecretory myeloma is more prevalent at later stages of the disease.

Oligosecretory myeloma, along with nonsecretory myeloma, is a subset of multiple myeloma. Nonsecretory myeloma patients have no measure­able levels of monoclonal (M) protein in their urine or blood. Similarly, oligosecretory myeloma patients have very low M-protein levels, also known as the M-spike, in their blood and urine.

These low or immeasurable levels of M-protein make it challenging for a patient's disease to be tracked using traditional blood and urine tests.  Until recently, the only way to mea­sure their M-protein levels and verify response to treatment was through frequent bone marrow biopsies.

Therefore, patients with oligosecretory and nonsecretory myeloma are typically not eligible to participate in clinical trials.

“We are trying to rectify a problem that has prevented a subset of myeloma patients from participating in clinical trials,” said Dr. Vincent Rajkumar, from the Mayo Clinic and one of the authors of the letter.

A relatively new test called the free light chain (FLC) assay, however, has made it possible to track the disease of many of these patients, allowing patients with oligosecretory myeloma to be included in clinical trials.

“Already many trials are starting to include patients with oligosecretory myeloma, and I hope this trend extends to all myeloma trials,” added Dr. Rajkumar.

Antibodies, which are produced by plasma cells, are made of two components: light chains and heavy chains.  Additionally, there are two types of light chains. Myeloma patients, including those with oligo­secre­tory and nonsecretory myeloma, tend to have an excess of one of the types of light chains in their blood stream.

The FLC assay measures the amounts of light chains in a patient’s blood and calculates the ratio of the two types of light chains.

“According to the International Myeloma Working Group response criteria, the FLC assay is adequate for response assessment in patients with oligosecretory myeloma, provided the ratio is abnormal and the baseline involved free light chain levels are 100 mg/L (10 mg/dL) or more,” Dr. Rajkumar told The Beacon.

The analysis discussed in the New England Journal of Medicine letter included 1,027 patients with newly diagnosed multiple myeloma.  Among those, 936 had undergone testing for M-protein levels in the blood and urine at the time of their diagnosis, and 141 had testing done after a third relapse.

The investigators found that significantly more patients with advanced disease (49 percent) had oligosecretory disease compared to newly diagnosed patients (9 percent).

Dr. Rajkumar believes that “as the disease progresses, the myeloma cells become more genetically abnormal and lose the ability to synthesize and/or secrete monoclonal proteins,” causing oligosecretory disease.

However, Dr. Rachid Baz from the Moffitt Cancer Center, who was not involved with the study, is not com­pletely convinced that oligosecretory disease becomes more prevalent in advanced stages of myeloma.

He explained that spikes in M-protein levels are high in newly diagnosed patients, but low after treatment, and that retreatment often begins before M-protein levels are measurable again.

“In this situation, the patient would be labeled as having oligosecretory disease while, in fact, if that patient had waited longer to start therapy, his/her M-spike may have reached measurable levels,” he said.

The results also show that the FLC assay can effectively measure light chain levels in many oligosecretory patients.  Specifically, 71 percent of newly diagnosed myeloma patients and 23 percent of advanced myeloma patients with oligosecretory disease had measurable light chain levels.

However, “in patients with lower levels of light chains and in those with true nonsecretory myeloma,” Dr. Rajkumar explained, “bone marrow assessment and imaging are critical for response assessment.”

Both Drs. Rajkumar and Baz agreed that more information is needed to verify the use of FLC assays as a tool for tracking disease progression.

Even though response criteria have already been published for oligosecretory patients, Dr. Baz said, “Few studies, including one by our group, have validated these response criteria.  It would be wise to have further validation.”

“We need to be able to demonstrate that the outcome of various response states as defined by the FLC assay (or other newer modalities) matches or exceeds the metrics obtained using M-protein levels,” explained Dr. Rajkumar.

For more information, please refer to the letter in the New England Journal of Medicine.