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Researchers Develop Model To Identify Myeloma Patients With MGUS-Like Disease

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Published: Jul 8, 2013 3:12 pm

Spanish researchers recently developed a new model based on a technique called multiparameter flow cytometry that can identify newly diagnosed multiple myeloma patients with disease profiles similar to those of patients with the myeloma precursor disease monoclonal gammopathy of undetermined significance.

The set of myeloma patients identified as having disease similar to monoclonal gammopathy of undetermined significance (MGUS) had better disease status at diagnosis and better long-term survival than other newly diagnosed myeloma patients, regardless of the depth of their response to treatment.

In addition, the model was able to identify MGUS and smoldering myeloma patients at high risk of progressing to symptomatic multiple myeloma.

The researchers believe that their model may serve as a biomarker to further stratify myeloma patients and ultimately help to define tailored therapies.

Background

Multiple myeloma patients who achieve a complete response to treatment typically have extended progression-free survival and overall survival compared to those who do not. However, prior research has shown that a subgroup of patients who do not reach a complete response, but revert to an MGUS-like profile after treatment, also have improved survival compared to other myeloma patients.

MGUS and smoldering multiple myeloma are precursors to multiple myeloma. Patients with either of these diseases have an increased level of monoclonal protein in the blood but none of the symptoms associated with multiple myeloma. The current standard of care is to regularly monitor patients with MGUS or smoldering myeloma but to hold off on treatment until their disease progresses. People with MGUS are less likely than those with smoldering myeloma to progress to multiple myeloma and typically have longer survival than those with smoldering or multiple myeloma.

According to the Spanish researchers, identifying myeloma patients with an MGUS-like profile may prevent the over-treatment of patients who achieve less than a complete response.

In the current study, the Spanish researchers sought to assess the utility of a new model that they developed based on a technique called multiparameter flow cytometry in identifying multiple myeloma patients with MGUS-like profiles.

Study Design

The study investigators analyzed data from 698 newly diagnosed myeloma patients who participated in one of two Spanish clinical trials. As a part of these trials, all patients underwent initial therapy, followed by high-dose chemotherapy and autologous stem cell transplantation. The median age at diagnosis was 58 years, and the median follow-up time was 5.9 years.

The study investigators compared the myeloma patient profiles to those of 497 MGUS patients.

In addition, they compared patient profiles of 114 smoldering myeloma patients to those of the MGUS and multiple myeloma patients.

Study Results

The researchers found that 8 percent of symptomatic myeloma patients had an MGUS-like profile. Patients with MGUS-like profiles were more likely to have lower-risk disease, higher hemoglobin levels, and lower tumor burden compared to patients with a typical myeloma profile. The researchers also found that the chromosomal abnormality del(13q) was less common among patients with an MGUS-like profile.

The researchers did not observe any significant differences in complete response rates between patients with an MGUS-like profile and patients with a typical myeloma profile.

However, patients with an MGUS-like profile had a longer median time to progression (not yet reached) compared to typical patients (44 months). MGUS-like patients also had a longer median overall survival (not yet reached) compared to patients with a typical profile (67 months).

Of all the symptomatic myeloma patients who did not reach a complete response, MGUS-like patients had a superior median time to progression (not yet reached versus 38 months) and overall survival (not yet reached versus 54 months) compared to patients with a typical myeloma profile. In addition, there were no significant differences in survival among MGUS-like patients who achieved a complete response and those who did not.

At ten years post-treatment, the progression-free survival rate was 28 percent for MGUS-like patients, compared to 4 percent for other symptomatic patients.  At the same time, the overall survival rate was 65 percent for MGUS-like patients, compared to 29 percent for other symptomatic patients.

The researchers also tested their model’s ability to predict the risk of disease progression in MGUS and smoldering myeloma patients.

They found that 1 percent of MGUS patients had profiles similar to those of symptomatic myeloma patients. Notably, the median time to progression for this subgroup was 7.1 years versus 19.5 years for standard MGUS patients.

Among patients with smoldering multiple myeloma, they found that patient profiles ranged from MGUS-like to symptomatic-like smoldering myeloma. Half (51 percent) of the patients had a standard smoldering myeloma profile, 36 percent had an MGUS-like profile, and 13 percent had a symptomatic myeloma-like profile.

The median time to progression differed significantly among smoldering multiple myeloma patients, with the median time to progression not reached for MGUS-like smoldering myeloma patients, 9 years for smoldering patients, and 15 months for symptomatic myeloma-like smoldering myeloma patients.

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

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3 Comments »

  • Dan D said:

    Curious whether free light chain ratio at time of diagnosis had any impact of whether the patient had an MGUS-like profile?

  • Elizabeth said:

    Dear Beacon Staff,

    I have a question about this statement:

    “The researchers also found that the chromosome abnomality del13(13q) was less common among patients with an MGUS-like profile.”

    Does this include patients with monosomy 13 or just 13q?

    Thank you,
    Elizabeth

  • Beacon Staff said:

    Dan D, the researchers did not report any results related to free light chain ratios.

    Elizabeth, the researchers only mention del(13q), not monosomy 13.