In 2005, a new staging system was developed by the IMF's research division, the International Myeloma Working Group (IMWG). Clinical and laboratory data were gathered on 10,750 previously untreated symptomatic myeloma patients from 17 institutions, including sites in North America, Europe, and Asia. Potential prognostic factors were evaluated using a variety of statistical techniques. Serum β2 microglobulin (Sβ2M), serum , platelet count, serum creatinine, and age emerged as powerful predictors of survival and were then further analyzed.

A combination of Sβ2M and serum provided the most powerful, simple, and reproducible three-stage classification. This system, the International Staging System (ISS), was further validated by demonstrating effectiveness

  • in patients in North America, Europe, and Asia;
  • in patients younger and older than age 65 years;
  • with standard therapy or auto transplant; and
  • in comparison with the Durie-Salmon Staging System.


International Staging System (ISS) for

Stage VALUES (β2M = Serum β2 microglobulin; ALB = serum
I Sβ2M < 3.5 mg/L; serum albumin ≥ 3.5 g/dL
II Sβ2M < 3.5 mg/L; serum albumin < 3.5 g/dL; or β2M 3.5 to 5.5 mg/L, irrespective of serum albumin
III Sβ2M > 5.5 mg/L


In August 2015, the IMWG published the Revised International Staging System (R-ISS) for to incorporate two further prognostic factors: genetic risk as assessed by fluorescence in-situ hybridization (FISH), and level of lactate dehydrogenase level (LDH).

Revised International Staging System (R-ISS)

Stage Criteria

Sβ2M < 3.5 mg/l

Serum ≥ 3.5 g/dl

Standard-risk chromosomal abnormalities (CA) by iFISH

Normal LDH

II Not R-ISS stage I or III

Sβ2M ≥ 5.5 mg/L and either

High-risk CA by


High LDH

What's Next?

If you are a newly diagnosed myeloma patient, learn when and if to begin treatment. Also, if you have undergone an induction therapy, learn about maintenance therapy and other new interventions.


The International Myeloma Foundation medical and editorial content team

Comprised of leading medical researchers, , oncologists, oncology-certified nurses, medical editors, and medical journalists, our team has extensive knowledge of the treatment and care landscape. Additionally, Dr. Brian G.M. Durie reviews and approves all medical content on this website.

Last Medical Review: August 1, 2019

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