Multiple myeloma international staging system: "staging" or simply "aging" system?

Area of Science:

• Hematology
• Oncology
• Geriatrics

Background:

• Multiple myeloma (MM) survival varies widely, prompting research into prognostic markers for over 40 years.
• The current MM International Staging System (ISS), using beta-2 microglobulin (β2M) and serum albumin (SA), is widely adopted but its precise rationale is unclear.
• Cytogenetic assessment and genomic approaches offer new perspectives for MM prognosis.

Purpose of the Study:

• To question the specific rationale of β2M and SA as MM prognostic markers.
• To highlight the role of β2M and SA as biomarkers of comorbidity in older adults.
• To propose that the MM-ISS may function as an aging system rather than a specific MM staging system.

Main Methods:

• Review of existing literature on MM prognostic factors.
• Analysis of the role of β2M and SA in MM and in age-related comorbidities.
• Consideration of cytogenetic and genomic data in MM staging.

Main Results:

• The prognostic efficiency of β2M and SA in MM is not fully understood.
• β2M and SA are established biomarkers for comorbidity burden in older adults.
• The MM-ISS may primarily reflect age-related comorbidity rather than MM-specific factors.

Conclusions:

• The MM-ISS should not be used alone for MM staging.
• Cytogenetics, potentially combined with MM-ISS, could serve as a standard prognostic method.
• Genomic factors may reveal both comorbidity and intrinsic MM clone malignancy, requiring further investigation for a future genomic classification.