A recently published Greek study provides updated data on the sig­nif­i­cance of MRI-detected focal lesions in the spine in patients with smol­der­ing myeloma.

The Greek study confirms that having more than one focal lesion in the spine puts a smoldering myeloma patient at a noticeably higher risk of progressing to multiple myeloma.

Focal lesions are areas of abnormal cells in the bone marrow. They are not lesions in the outer (hard) area of the bone – lesions which are often called "lytic" lesions.

The Greek researchers found that the smoldering myeloma patients in their study who had more than one focal lesion in the spine progressed to symptomatic multiple myeloma within a median of 15 months, compared to a median of more than five years for smoldering myeloma patients with no focal lesions in their spines.

Among the patients with more than one focal lesion in their spine, 85 percent progressed to multiple mye­lo­ma within three years, compared to 22 percent for patients with no focal lesions in the spine.

These findings are in line with previous research, including a recent German study that showed that focal lesions found by whole-body MRI scans identify smoldering myeloma patients at high risk for disease progression (see related Beacon news).

The Greek study, however, used MRI scans of the spine, rather than whole-body MRI scanning, to identify focal lesions. According to the Greek researchers, MRIs of the spine are much more widely available than whole-body MRI scanning. They are also less time consuming, less expensive, and typically more com­fort­able for patients than whole-body MRI scans.

Based on their findings, the Greek researchers conclude that MRI of the spine should be the imaging meth­od of choice for the identification of patients with smoldering myeloma who are at high risk for pro­gres­sion to symptomatic disease.

Results of such imaging, the researcher argue, can easily be combined with other readily available test results – such as a patient's bone marrow plasma cell percentage and free light chain ratio – to clearly identify high-risk smoldering who, in the researchers' opinions, "should be offered immediate therapy, just like patients with symptomatic multiple myeloma."

Background

Smoldering, or asymptomatic, myeloma is a precursor to multiple myeloma in which certain signs of the disease are present, such as plasma cells in the bone marrow or elevated blood protein levels.  However, smoldering myeloma patients by definition have none of the “CRAB” symptoms typically associated with active (symptomatic) multiple myeloma, such as excessive calcium in the blood, kidney (renal) disease, anemia, or lytic bone lesions.

Across all smoldering myeloma patients, the risk of progression from smoldering to symptomatic disease is around 10 percent during each of the first five years after diagnosis, and decreases to 3 percent per year for the following five years, and to 1 percent per year thereafter.  This pattern of risk of progression translates into a median time to progression of about five years from the time a person is diagnosed with smoldering myeloma.

Although smoldering myeloma patients are at a higher risk of developing symptomatic myeloma than the general public, the current standard of care is the so-called “watch and wait” approach, in which smoldering myeloma patients are regularly monitored and treatment only begins once the disease progresses to symp­tom­atic multiple myeloma.

Research in the recent years has shown that several measures may be useful for identifying smoldering myeloma patients who are at a particularly high risk of progressing to symptomatic myeloma sooner rather than later.  Such measures include the results of MRI scans, which can identify focal lesions in the bone marrow.  The presence of such lesions at the time of diagnosis has been linked to a higher risk of pro­gres­sion.

In the current study, the Greek researchers sought to confirm the findings of previous studies showing that focal lesions detected by MRIs of the spine have an important impact on time to pro­gres­sion in smoldering myeloma.

Study Design

Researchers from the University of Athens in Greece retrospectively analyzed the records of 67 patients with smoldering myeloma who had a minimum follow-up time of 2.5 years.

The median patient age at diagnosis was 63 years; 63 percent of patients had IgG smoldering myeloma, and 37 percent had IgA smoldering myeloma.

The median M-spike based on blood testing was 1.9 g/dL, and the median free light chain ratio was 7.6, with 11 percent of the patients having a ratio of 100 or more.

(The free light chain ratio for each patient was calculated by dividing the level of their "involved" free light chain by the level of their "uninvolved" free light chain.  Someone who has IgG lambda smoldering myeloma, for example, would have their ratio calculated by dividing their lambda light chain level by their kappa light chain level.)

At the time of diagnosis, 20 percent of patients had abnormal findings in the MRIs of the spine; 16 percent (11 patients) had one or more focal lesions, and 14 percent (9 patients) had more than one focal lesion in the spine at diagnosis.

This pattern of focal lesions in the spine is in line with what has been seen in previous studies, which have found that about 15 percent of smoldering myeloma patients have one or more focal lesions in their spines, based on MRI scans, at the time of diagnosis.

The median follow-up time in the current study was four years.

Study Results

The Greek researchers found that smoldering myeloma patients with more than one focal lesion in their spine progressed to symptomatic multiple myeloma within a median of 15 months, compared to a median of more than five years for smoldering myeloma patients with no focal lesions.

The three-year progression rate for patients with more than one focal lesion was 85 percent, com­pared to 22 percent for patients with no focal lesions.

Based on the findings of previous studies, the Greek researchers next defined three characteristics that could help identify patients at a higher risk of progression from smoldering to symptomatic myeloma:

1. Having a bone marrow plasma cell percentage of 60 percent or more
2. Having a free light chain ratio of more than 100
3. Having more than one focal lesion in the spine.

The researchers found that 15 percent of the patients included in their analysis had at least one of these high-risk characteristics.  Among the patients with more than one focal lesion in their spine, 67 percent had at least one of the other high-risk features.

The median time to progression for patients with at least one of the high-risk characteristics was just nine months, com­pared to more than five years for those with none of the high-risk features.

The three-year progression rate was 89 percent for patients with at least one of the high-risk feature, com­pared to 21 percent for those with none of the high-risk characteristics.

Given that it is relatively easy for smoldering myeloma patients to be tested to see if they have any of the three high-risk features they specified, the Greek researchers recommend that such testing be done routinely -- including MRI of the spine.

Although whole-body MRI scanning may be more comprehensive than an MRI of the spine in identifying focal lesions in smoldering myeloma patients, the study authors note that it is whole-body MRI scanning is not widely available and it also is expensive.

In addition, the German study mentioned earlier, which looked at whole-body MRI in smoldering myeloma patients, found that only about 10 percent of smoldering myeloma patients who do not have focal lesions in their spine at diagnosis have one or more focal lesions outside the spine.

Thus, the Greek researcher feel the three characteristics they identify make it easy and inexpensive for physicians to identify smoldering myeloma patients who are at a high risk of progressing soon to symp­tom­atic multiple myeloma.

For more information, please see Greek researchers' letter to the editor in the journal Leukemia (subscription required).