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.
Use only in patients recently diagnosed with multiple myeloma. Do not use in patients with relapsed myeloma, smoldering myeloma or MGUS. Its utility has NOT been validated in relapsed myeloma, smoldering myeloma or MGUS patients.
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.
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.
|Serum β2 microglobulin||<3.5 mg/L|
|Serum albumin||<3.5 g/dL|
|CA by iFISH|
High risk defined as: presence of del(17p) and/or translocation t(4;14) and/or translocation t(14;16)
|LDH||Normal (< upper limit of normal)|
|High (> upper limit of normal)|
First, assign ISS stage:
|Serum albumin, g/dL|
|Serum β2 microglobulin, mg/L||<3.5||ISS I||ISS II|
|3.5-5.4||ISS II||ISS II|
|≥5.5||ISS III||ISS III|
Then, stage R-ISS according to iFISH and LDH:
|High-risk cytogenetic abnormalities by iFISH*|
|ISS I||R-ISS I||R-ISS II||Normal||LDH|
|R-ISS II||R-ISS II||High|
|ISS IІ||R-ISS II||R-ISS II||Normal|
|R-ISS II||R-ISS II||High|
|ISS IІІ||R-ISS II||R-ISS III||Normal|
|R-ISS III||R-ISS III||High|
*High-risk = presence of del(17p) and/or translocation t(4;14) and/or translocation t(14;16).
|R-ISS Stage||Median progression-free survival|
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.
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.
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
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- Palumbo A, et. al. Revised International Staging System for Multiple Myeloma: a Report From International Myeloma Working Group. JCO 2015; 33: 2863-2869.
- Greipp PR, et. al. International Staging System for Multiple Myeloma. JCO 2005; 23:3412-3420.
- International Myeloma Foundation. International Staging System. April 2002.
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