Multiple Myeloma is a cancer of the plasma cells, a type of white blood cell that produces infection-fighting antibodies. The disease originates in the bone marrow, where cancerous plasma cells multiply and can damage the bones, kidneys, and immune system. Physicians use staging to determine the extent and seriousness of the disease, which guides the initial approach to patient care.
Understanding the Need for Classification
Staging provides a standardized way to describe the amount of cancer present at diagnosis. Because Multiple Myeloma has a highly variable course, classification is important for predicting prognosis. Unlike solid tumors, which are staged by size and spread, Multiple Myeloma is a blood-based cancer requiring a different approach. This standardization allows physicians to stratify patients into risk groups, ensuring those with similar disease biology receive comparable treatments.
The International Staging System
The International Staging System (ISS), established in 2005, is the foundation for modern classification. This simple, three-stage system relies on the levels of two specific blood markers: serum beta-2 microglobulin (\(\beta_2\)-M) and serum albumin. Elevated \(\beta_2\)-M levels reflect a higher tumor burden and advanced disease, while lower albumin levels are linked to increased disease activity. Stage I is the most favorable, characterized by low \(\beta_2\)-M (less than 3.5 mg/L) and high albumin (3.5 g/dL or greater). Stage III represents the highest-risk group, defined by significantly elevated \(\beta_2\)-M (5.5 mg/L or greater), regardless of albumin level.
Refining the Classification: The R-ISS
Recognizing the need for a more accurate prognostic tool, the Revised International Staging System (R-ISS) was developed in 2015. The R-ISS uses the original ISS stage but integrates additional high-risk factors to better stratify patients. These factors include the level of lactate dehydrogenase (LDH), an enzyme often signaling aggressive cancer cells, and specific high-risk chromosomal abnormalities detected via Fluorescence In Situ Hybridization (FISH). These genetic features include deletion 17p, t(4;14), or t(14;16). The R-ISS creates three stages (R-ISS I, II, and III) that combine standard blood markers with molecular details, as the presence of these genetic changes automatically elevates a patient’s risk classification.
Staging and Treatment Planning
The R-ISS stage is instrumental in translating complex medical data into actionable decisions for the patient’s treatment plan. R-ISS Stage I corresponds to the lowest-risk group, Stage II to an intermediate-risk group, and Stage III to the highest-risk group. This risk stratification directly influences the intensity and selection of initial therapy, often called induction therapy. Patients classified as having higher-risk disease (Stage III) may be candidates for more aggressive treatment combinations to maximize the initial response. The stage also determines eligibility for high-dose chemotherapy followed by autologous stem cell transplantation, and informs the choice of maintenance therapy, which is a continuous, lower-dose treatment given after initial therapy to keep the cancer in remission.