Multiple myeloma staging

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Hannan Javed, M.D.[2]; Haytham Allaham, M.D. [3]; Shyam Patel [4]

Overview

Multiple myeloma may be divided into three stages based on either the International Staging System (ISS) or Durie-Salmon Staging System.^[1] The International Staging System for multiple myeloma was published by the International Myeloma Working Group in 2003 and is the most widely used staging system.^[1]^[2] It is used for both guiding treatment as well as predicting prognosis. The Durie-Salmon staging system, first published in 1975, is a clinical staging system for multiple myeloma that correlates measured myeloma cell mass to the presenting clinical features, response to treatment, and survival.^[3] Durie-Salmon Staging System is still in use, but has been largely superseded by the more practical ISS and revised ISS ^[1]

Staging

International Staging System

According to the International Staging System (ISS), there are three stages of multiple myeloma based on both β₂-microglobulin and albumin levels:^[1] ^[2]


Stage	Features	Prognosis

Stage 1	β₂-microglobulin <3.5 mg/L and albumin ≥3.5 g/dL	Median survival of 62 months
Stage 2	β₂-microglobulin <3.5 and albumin <3.5 or β₂-microglobulin 3.5-5.5 mg/L	Median survival of 45 months
Stage 3	β₂-microglobulin >5.5	Median survival of 29 months

Revised International Staging System

The Revised International Staging System (R-ISS) was proposed in 2015 and incorporated chromosomal aberrations and LDH level to more accurately risk stratify patients.^[4]


Stage	Features	Prognosis

Stage 1	β₂-microglobulin <3.5 mg/L and albumin ≥3.5 g/dL and Absence of high-risk chromosomal abnormalities such as del(17p), t(4;14), or t(14;16) and Normal LDH level	5-year overall survival of 82% 5-year progression-free survival of 55%
Stage 2	Not Stage 1 or Stage 3	5-year overall survival of 62% 5-year progression-free survival of 36%
Stage 3	β₂-microglobulin >5.5 mg/L, and Presence of high-risk chromosomal abnormalities such as del(17p), t(4;14), t(14;16) or Elevated LDH level	5-year overall survival of 40% 5-year progression-free survival of 24%

Durie-Salmon Staging System

According to the Durie-Salmon Staging System, there are three stages of multiple myeloma based on the hemoglobin level, calcium level, skeletal survey, serum paraprotein level, and urinary light chain excretion:^[1]


Stage	Hemoglobin level	Calcium level	Skeletal survey	Serum paraprotein level	Urinary light chain excretion

Stage 1	>10g/dL	8.5-10.2 mg/dL	Normal or single plasmacytoma or osteoporosis	<5 g/dL if IgG or <3 g/dL if IgA	<4 g/24h
Stage 2	8.5-10g/dL	10.2-12 mg/dL	Fulfilling the criteria of neither 1 nor 3	5-7 g/dL if IgG or 3-5 g/dL if IgA	4-12 g/24h
Stage 3	<8.5g/dL	>12mg/dL	3 or more lytic bone lesions	>7g/dL if IgG or > 5 g/dL if IgA	>12g/24h

Stages 1, 2 and 3 of the Durie-Salmon staging system can be divided into A or B depending on serum creatinine:^[1]

A: serum creatinine < 2 mg/dL (< 177 umol/L)
B: serum creatinine > 2 mg/dL (> 177 umol/L)

SWOG Staging System

The Southwest Oncology Group (SWOG) staging system is not currently widely used. Unlike the other staging systems, there are four stages in the SWOG staging system.^[5]


SWOG Staging System

Stage	Features
Stage 1	β₂-microglobulin <2.5 mg/L
Stage 2	β₂-microglobulin >2.5 mg/L and <5.5 mg/L
Stage 3	β₂-microglobulin5.5 mg/L and albumin >3 g/dl
Stage 4	β₂-microglobulin>5.5 mg/L and albumin <3 g/dl

References

↑ ^1.0 ^1.1 ^1.2 ^1.3 ^1.4 ^1.5 About multiple myeloma. University of California San Francisco (2015)http://cancer.ucsf.edu/research/multiple-myeloma/ Accessed on September, 18 2015
↑ ^2.0 ^2.1 Greipp PR, San Miguel J, Fonseca R, Avet-Loiseau H, Jacobson JL, Rasmussen E, Crowley J, Durie BMG. Development of an international prognostic index (IPI) for myeloma: report of the international myeloma working group. Hematology Journal 2003;4:S42. NLM ID 100965523.
↑ Durie BG, Salmon SE (1975). “A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival”. Cancer. 36 (3): 842–54. PMID 1182674.
↑ Palumbo A, Avet-Loiseau H, Oliva S, Lokhorst HM, Goldschmidt H, Rosinol L; et al. (2015). “Revised International Staging System for Multiple Myeloma: A Report From International Myeloma Working Group”. J Clin Oncol. 33 (26): 2863–9. doi:10.1200/JCO.2015.61.2267. PMC 4846284. PMID 26240224.
↑ Choi JH, Yoon JH, Yang SK (2007). “Clinical value of new staging systems for multiple myeloma”. Cancer Res Treat. 39 (4): 171–4. doi:10.4143/crt.2007.39.4.171. PMC 2739370. PMID 19746184.

[California-1] 1.0 ^1.1 ^1.2 ^1.3 ^1.4 ^1.5 About multiple myeloma. University of California San Francisco (2015)http://cancer.ucsf.edu/research/multiple-myeloma/ Accessed on September, 18 2015

[ISS-2] 2.0 ^2.1 Greipp PR, San Miguel J, Fonseca R, Avet-Loiseau H, Jacobson JL, Rasmussen E, Crowley J, Durie BMG. Development of an international prognostic index (IPI) for myeloma: report of the international myeloma working group. Hematology Journal 2003;4:S42. NLM ID 100965523.

[pmid1182674-3] Durie BG, Salmon SE (1975). “A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival”. Cancer. 36 (3): 842–54. PMID 1182674.

[pmid26240224-4] Palumbo A, Avet-Loiseau H, Oliva S, Lokhorst HM, Goldschmidt H, Rosinol L; et al. (2015). “Revised International Staging System for Multiple Myeloma: A Report From International Myeloma Working Group”. J Clin Oncol. 33 (26): 2863–9. doi:10.1200/JCO.2015.61.2267. PMC 4846284. PMID 26240224.

[pmid19746184-5] Choi JH, Yoon JH, Yang SK (2007). “Clinical value of new staging systems for multiple myeloma”. Cancer Res Treat. 39 (4): 171–4. doi:10.4143/crt.2007.39.4.171. PMC 2739370. PMID 19746184.

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