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Regular Whole-Body MRI Scans May Identify Smoldering Myeloma Patients At High Risk For Progression

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Published: Mar 17, 2014 4:47 pm

Results from a German retrospective study show that repeated whole-body mag­netic resonance imaging may identify smoldering myeloma patients with an increased risk of progressing to symptomatic multiple myeloma.

In their study, the German researchers looked at smoldering myeloma patients who had whole-body magnetic resonance imaging (MRI) scans at the time of diagnosis and during regular follow-up visits.

The researchers found that patients whose follow-up scans showed pro­gres­sion of their disease had a 16.5-fold higher risk of progressing to symptomatic myeloma than patients who had stable disease based on their follow-up scans.

The investigators defined disease progression based on follow-up scans to occur when such scans de­tected new or larger focal lesions, or when the scans detected expansion in any diffuse bone marrow in­fil­tration.

Diffuse bone marrow infiltration occurs when cancerous cells replace normal bone marrow.  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.”

Patients who did not show evidence of MRI-progressive disease during follow-up did not have an increased risk of progression to symptomatic myeloma, even if they had focal lesions at diagnosis.

The results of the current study expand on those of previous studies, which have shown that whole-body MRI is useful in identifying patients with a myeloma precursor disease who are at a risk of progressing to symp­to­matic myeloma.

One previous study looked at patients with monoclonal gammopathy of undetermined significance (MGUS) (see related Beacon news), while a second study looked at patients with smoldering myeloma (see related Beacon news).

Based on their findings, the German researchers conclude that whole-body MRI "is the best imaging method for ... follow-up of smoldering multiple myeloma patients."

They also believe such follow-up is important because it may help identify patients who are at high risk of progression, and who therefore might benefit from early treatment.

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 bone involvement.

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, which means that the median time to pro­gression is about five years.

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 in identifying smol­der­ing myeloma who are at a particularly high risk of progressing to symptomatic myeloma sooner rather than later.  Such measures include the results of whole-body 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 German researchers sought to determine the prognostic significance of follow-up whole-body MRI scans in patients with smoldering myeloma. They hypothesized that the development of progressive disease as detected by MRI might be an indication of a higher risk of progression to symp­to­matic multiple myeloma.

Study Design

Researchers from the University Hospital in Heidelberg, Germany, retrospectively analyzed the records of 63 patients with smoldering myeloma who had received at least two MRIs as part of their follow-up between July 2004 and January 2013.

The median age at the first MRI was 55 years old.

Patients who developed new or larger focal lesions, or new or progressive diffuse bone marrow infiltration, over the course of multiple MRIs were characterized as having MRI-progressive disease.

Patients who did not develop new or larger focal lesions, or new or progressive diffuse bone marrow in­fil­tra­tion, were characterized as having MRI-stable disease.

The median follow-up time was 5.4 years.  The median time between each MRI a patient in the study received was just under a year.

Study Results

Initial MRIs detected focal lesions in 33 percent of the smoldering myeloma patients, and diffuse bone marrow infiltration without focal lesions in 30 percent of patients. The remainder of the patients (38 percent) did not show any bone marrow involvement during their initial MRI.

In the first five years after the initial MRI, 40 percent of the patients progressed to symptomatic disease. The majority of these patients (76 percent) progressed based on the development of lytic bone lesions. An additional 12 percent progressed due to anemia, 4 percent due to high calcium levels, and 4 percent due to kidney failure.

Overall, 49 percent of the patients showed MRI-progressive disease during follow-up MRIs; 33 percent developed new or larger focal lesions, and 16 percent showed only progressive diffuse bone marrow infiltration.

Among the patients in the study who eventually progressed to symptomatic multiple myeloma, almost all were patients who had MRI-progressive disease.

Overall, patients with MRI-progressive disease had a 16.5-fold higher risk of progression to symptomatic myeloma compared to patients with MRI-stable disease.

Additionally, patients who had MRI-stable disease did not have an increased risk of progression even if they had focal lesions or diffuse bone marrow infiltration observed during their first MRI.

There were, however, two factors observed at diagnosis that were associated with an increased risk of progression to symptomatic myeloma even after taking into account whether or not a patient later experienced MRI-progressive disease.

The first was whether or not the patient had a monoclonal protein levels of 2.0 g/dL or higher at diagnosis.

The second was whether or not 95 percent or more of the plasma cells in the patient's bone marrow at diagnosis were "aberrant, " meaning that they had one or more of the following three chromosomal abnormalities: del(17p), t(4;14), or 1 q gain (+1q21).

Patients in the study who experienced MRI-progressive disease did not show any noticeable change in the M-spike levels as this progression occurred.  They did experience, however, a noticeable lowering of their hemoglobin levels.

For further information, see the complete study:  Merz M et al., "Predictive value of longitudinal whole-body magnetic resonance imaging in patients with smoldering multiple myeloma," Leukemia, February 18, 2014 (doi:10.1038/leu.2014.75) (abstract).

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4 Comments »

  • Dana H said:

    Hi Beacon Staff,

    Thanks for this very informative article. Do you know how many MM centers currently utilize this type of WB-MRI or is it presently limited to research for now?

    Do you anticipate if these will become more readily available in the followup process for those w/ Smoldering MM?

    Additionally, regarding the t(11;14), t(6;14) or trisomes? Were these abnormalities highlighted as aberrant cells? Would a percentage of >95 of these types of cells carry the same risk of progression?

    Your assistance is always appreciated.

    Dana H.

  • Myeloma Beacon Staff said:

    Hi Dana,

    As we understand it, whole-body (or full-body) MRI scans can be done in most major cities, and not necessarily just at major research centers. However, the scans are not cheap, which is one of the main reasons it's not used extensively.

    Regarding the chromosomal abnormalities mentioned at the end of the article ... The authors of the current study had done previous work, discussed in this Beacon article,

    http://www.myelomabeacon.com/news/2013/11/06/chromosomal-abnormalities-tumor-load-smoldering-myeloma-progression-risk/

    that identified these three chromosomal abnormalities as being linked to a higher risk of progression to symptomatic myeloma in smoldering myeloma patients.

    They therefore chose to define "aberrant" plasma cells in the bone marrow as those that had one or more of the three listed chromosomal abnormalities.

    The increased risk of progression to symptomatic myeloma if a patient had 95 percent or more aberrant plasma cells at diagnosis was about half the increased risk if the patient later experienced MRI-progressive disease. That's additional risk, however, above and beyond the risk associated with experiencing MRI-progressive disease.

  • Susan in RI said:

    Were the MRIs done with or without contrast and if with contrast, was gadolinium used?

  • Myeloma Beacon Staff said:

    Hi Susan,

    The MRIs for this study were performed without the use of any contrast agent. This is mentioned in the paper, but we also double checked with the authors to make sure our understanding of the relevant information in the paper is correct.

    Dr. Maximilian Merz, lead author of the study, also told us that, currently at the center where the study was carried out, "contrast agent ... is only applied in clinical studies to assess bone marrow microcirculation".