Results from a recent study indicate that the two leading models for classifying smoldering myeloma patients based on their risk of disease progression disagree significantly more often than they agree.

The two models were developed independently by researchers at the Mayo Clinic and the Spanish 'PETHEMA' working group.

Given the results of their comparison, the authors of the current study argue that further studies are needed to define a more broadly applicable set of criteria to assess a smoldering myeloma patient’s risk of progression.

The current study did not assess which of the existing two models is more accurate at predicting a smoldering myeloma patient's risk of progression.

Smoldering  myeloma is a precursor to multiple myeloma in which the patient does not display any of the typical myeloma-related symptoms, such as elevated calcium levels, kidney damage, anemia, or bone lesions. Compared to the general population, smoldering myeloma patients are at a higher risk of developing symptomatic (active) myeloma.

Results from recent studies indicate that the risk of progression from smoldering to symptomatic myeloma is 10 percent per year for the first five years after a smoldering myeloma patient's diagnosis. This risk reduces to 3 percent per year for the next five years, and to 1 percent per year thereafter.

However, the risk of progression varies significantly among patients.

The current standard of care for smoldering myeloma is a ‘watch and wait’ approach, which involves monitoring the patient regularly and beginning treatment only once the disease progresses to symptomatic myeloma.  This approach is based on previous evidence that treatment at this stage of the disease does not have an impact on overall survival, yet exposes patients to chemotherapy – and therefore side effects – for a longer period of time.

However, recent studies have begun to show that treatment may delay disease progression and even extend overall survival for certain smoldering myeloma patients at high risk of progressing to active myeloma (see related Beacon news and related interview).

The authors of the current study point out that finding reliable markers that indicate a high risk for disease progression would allow researchers to more effectively design clinical trials to delay or prevent the onset of active multiple myeloma.

They argue that with better assessments of progression risk, clinicians could improve counseling and identify smoldering myeloma patients who would benefit most from early treatment.

There are currently two models used by myeloma specialists to evaluate a smoldering myeloma patient’s risk of progression to active myeloma.  One was developed by researchers at the Mayo Clinic, the other by myeloma specialists in the PETHEMA working group of the Spanish Society of Haematology and Hemotherapy.

These models were derived from retrospective studies in which researchers identified patient characteristics present at the time of a smoldering myeloma diagnosis that were later associated with disease progression.

In the current study, investigators at the National Cancer Institute in Bethesda, Maryland, assessed the risk of progression in smoldering myeloma patients using both the Mayo Clinic model and the Spanish model.

The prospective study enrolled 77 smoldering myeloma patients between April 2010 and July 2012. Each patient in the study was categorized as low risk, intermediate risk, and high risk for progression to multiple myeloma using both the Mayo Clinic and Spanish (PETHEMA) model.

The two models frequently disagreed in terms of their risk assessment of each patient.

In fact, the models agreed just 29 percent of the time.

Using the Mayo Clinic model, 38 patients were categorized as low-risk, 35 as intermediate-risk, and 4 as high-risk.

The Spanish model, on the other hand, classified 17 patients as low-risk, 22 as intermediate-risk, and 38 as high-risk.

Among the 38 patients classified as high-risk by the Spanish model, only 10 percent were considered high-risk by the Mayo Clinic model.

Furthermore, of the 38 patients categorized as low-risk by the Mayo Clinic model, only 29 percent were also classified as low-risk according to the Spanish model.

According to the study investigators, the significant disagreement between the two models highlights the need for a more reliable model of progression risk.

For more information, please see the study in Leukemia and Lymphoma (abstract).