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    Multiple Myeloma International Staging System (ISS)

    Prognosticates the severity of multiple myeloma based on routinely obtained lab values.
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    INSTRUCTIONS

    Use only in patients recently diagnosed with multiple myeloma. Do not use in patients with relapsed myeloma, smoldering myeloma or MGUS.

    When to Use
    Pearls/Pitfalls
    Why Use

    Newly diagnosed MM patients. Its utility has not been validated in relapsed myeloma, smoldering myeloma or MGUS patients.

    • The International Staging System (ISS) for multiple myeloma defines 3 subgroups with differing overall survival:
      • Stage I- 62 months
      • Stage II- 44 months
      • Stage III- 29 months
    • The ISS was developed as a simpler, more objective tool to provide prognostic information for newly diagnosed, symptomatic MM patients.
    • It does not reflect disease burden.
    • Durie-Salmon, a cumbersome staging system used in the past, was based on estimating the disease burden but ultimately did not prove to be prognostic and fell out of favor.
    • Compared to older staging systems, ISS is a simple prognostic tool and may be used to stratify patients on MM clinical trials.
    • Multiple myeloma (MM) is a heterogeneous disease, with prognosis affected by various patient and disease related factors (ISS stage, genetics, performance status and other comorbidities).
    • The ISS differentiates patients into 3 separate prognostic groups. The staging is prognostic but does not necessarily guide treatment decisions in the upfront setting. It provides survival information to the physician and patient, and helps stratify patients in current clinical trials.
    • Preferred over the Durie-Salmon system for its simplicity and objectivity, primarily in assessment of bony disease.

    Result:

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    Next Steps
    Evidence
    Creator Insights

    Advice

    Many MM patients are treated through clinical trials. Physicians may consider referring patients to academic treatment centers if they are eligible and willing to receive transplantation, not only to discuss standard treatment options, but also to consider clinical trial options.

    Formula

    Staging based on serum β2 microglobulin and albumin levels.

    Facts & Figures

    Multiple Myeloma ISS interpretation:

    Stage Criteria
    I Serum β2 microglobulin <3.5 mg/L AND serum albumin ≥ 3.5 g/dL
    II Either: serum β2 microglobulin <3.5 mg/L, but serum albumin <3.5 g/dL
    OR
    serum β2 microglobulin 3.5 – 5.4 mg/L irrespective of the serum albumin
    III Serum β2 microglobulin ≥5.5 mg/L

    Evidence Appraisal

    • This system was developed from a database of clinical and laboratory data collected from 10,750 patients treated from 1981 to 2002. All patients were about to start therapy, ~70% through a clinical trial, and were from North America, Europe, and Asia. Approximately 25% received high-dose therapy/stem cell transplant. Median age was 60-63 years.
    • A randomly selected training set was created and analyzed by univariate and multivariate analysis, selecting serum beta-2 microglobulin and serum albumin as the dominant independent prognostic factors, best utilized in a survival tree model.
    • This model classified patients in 3 risk groups:
      • Stage I- median overall survival 62 months;
      • Stage II- 45 months;
      • Stage III- 29 months.
    • The ISS was then validated in a separate group of patients from the same database with virtually identical results. It was validated further by geography, patient age, and treatment type.
    • This model has been refined further as the Revised ISS (R-ISS). It includes validated and reliable prognostic factors for MM, including ISS score, cytogenetic abnormalities, and LDH. It identifies 3 groups with clearly different outcomes. It recharacterized ~ 25% of patients who would have been identified as good risk using only one of the validated factors into a higher risk category.
    Dr. Philip Greipp

    About the Creator

    Philip Greipp, MD, is a professor laboratory medicine and pathology at the Mayo Clinic in Rochester, Minnesota. He is practices primarily in the Hematology Department, but has a joint appointment in the Laboratory Medicine and Pathology Department. He has been a supporting author on over 100 publications in numerous peer-reviewed journals on topics ranging from cardiac enzymes to hematologic cancers and novel treatment methods.

    To view Dr. Philip Greipp's publications, visit PubMed

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