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    • Disease is diagnosed: prognosticate to guide treatmentPrognosis
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    Patent Pending

    Revised Multiple Myeloma International Staging System (R-ISS)

    Prognostication tool for myeloma patients based on the genetics and other routinely used lab values in conjunction with the original ISS Staging System.
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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 revised International Staging System (R-ISS) for multiple myeloma was developed to better prognosticate long term outcomes of myeloma patients using easily obtained and routinely used prognostic variables.
    • It includes the parameters from the International Staging System (ISS), as well as cytogenetic abnormalities (CA) serum lactate dehydrogenase (LDH).
    • The R-ISS creates 3 subgroups with significantly different overall survival:
      • Stage I: 82%
      • Stage II: 62%
      • Stage III: 40%
    • It risk-stratifies multiple myeloma patients better than the original ISS.
    • 40% of patients in the data set were not transplant eligible, which reflects a more real-world population than does previous studies
    • Provides better discrimination of prognosis for MM by using simple, readily available variables.
    • Reliable, validated tool that may have a role in upfront risk stratification in future clinical trials, and also may help patients understand their prognosis better.
    About the Creator
    Dr. Antonio Palumbo
    Content Contributors
    • Randall Pierce, MD

    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.

    Management

    • Current staging systems provide prognostic information and are useful for stratification and data assessments/comparisons.
    • The R-ISS, though a more robust powerful prognostic tool compared to ISS, is NOT directly used to alter treatment recommendations outside of a clinical trial at this time.

    Formula

    • Stages based on serum β2 microglobulin and albumin levels for the ISS; iFISH assessment for del(17p), t(4;14), and t(14;16); and serum LDH measurement.
    • CAs are detected by interphase fluorescent in situ hybridization (iFISH). Deletion of 17p [del (17p)], and translocations (4;14) and (14;16) are considered high risk; absence of these, including any other findings are standard risk.

    Facts & Figures

    R-ISS interpretation:

    R-ISS Stage Criteria
    I ISS stage I AND standard-risk of CA by iFISH AND normal LDH
    II Not R-ISS stage I or III
    III ISS stage III AND high-risk CA by iFISH OR high LDH

    Evidence Appraisal

    • The revised ISS is based on the original ISS for MM and has been refined further to include validated and reliable prognostic factors for MM, including ISS score, cytogenetic abnormalities, and LDH.
    • It identifies 3 groups with clearly different outcomes and recharacterized ~25% of patients who would have been identified as good risk (misclassified as “good prognosis”) using only one of the validated factors into a higher risk category.
    • Unlike several other studies, the data set includes many patients (40%) that were not transplant eligible, thus reflecting a “real-world” population.
    Dr. Antonio Palumbo

    About the Creator

    Antonio Palumbo is chief of the Myeloma Unit of the Department of Oncology, Section of Hematology at the University of Torino. He is currently a member of the Board of Directors of the International Myeloma Society. Dr. Palumbo's research focuses on plasma cell dyscrasia, and the pathogenesis and treatment of multiple myeloma.

    To view Dr. Antonio Palumbo's publications, visit PubMed

    Content Contributors
    • Randall Pierce, MD