What is the Revised International Staging System (R-ISS) and how is it used in the diagnosis of multiple myeloma (MM)?

Updated: Mar 06, 2020
  • Author: Dhaval Shah, MD; Chief Editor: Emmanuel C Besa, MD  more...
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The International Working Group noted that these findings have been “associated with near inevitable development of CRAB features in patients who would otherwise be regarded as having smouldering multiple myeloma.” [128]  The presence of any of the CRAB criteria or any of these three additional criteria justifies therapy.


In 2015, the  International Myeloma Working Group published the Revised International Staging System for Multiple Myeloma. [130] The revised system was subsequently recommended by the NCCN. [2]  The Revised International Staging System (R-ISS) was created by combining the International Staging System (ISS) with chromosomal abnormalities (CA) detected by interphase FISH (iFISH) after CD138 plasma cell purification, plus serum LDH assay results . [130]

Like the ISS, the R-ISS is based on three stages. Stage I criteria are as follows:

  • Beta-2 microglobulin ≤3.5 g/dL and albumin ≥3.5 g/dL
  • Standard risk for CA
  • Normal LDH

Stage II comprises patients who do not meet criteria for stage I or stage III

Stage III consists of the following:

  • Beta-2 microglobulin of 5.5 g/dL or more,   and either
  • High risk for CA  or high LDH

Median progression-free survival is as follows:

  • Stage I : 66 months
  • Stage II: 42 months
  • Stage III: 29 months

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