From the Guidelines
Multiple myeloma risk classification should be based on the Revised International Staging System (R-ISS), which categorizes patients into three risk groups to guide treatment decisions and predict outcomes. This system evaluates serum albumin, beta-2 microglobulin, lactate dehydrogenase (LDH) levels, and specific cytogenetic abnormalities, as outlined in the 2019 ASCO and CCO joint clinical practice guideline 1. The R-ISS incorporates the original ISS (serum B2M and serum albumin), while adding prognostic information obtained from the serum LDH and chromosomal abnormalities (CAs) detected by plasma cell–specific interphase FISH.
Key Components of R-ISS
- Serum albumin and beta-2 microglobulin levels
- Lactate dehydrogenase (LDH) levels
- Specific cytogenetic abnormalities, including del(17p), t(4;14), and t(14;16) The R-ISS stages are defined as follows:
- Stage I: ISS stage I with normal LDH and standard-risk CA
- Stage II: Neither stage I nor stage III
- Stage III: Stage III ISS (b2 M $ 5.5 mg/dL) with high LDH and/or high-risk CA
Implications for Treatment
Patients with R-ISS stage I, II, and III had 5-year OS rates of 82%, 62%, and 40%, respectively, as reported in the 2019 guideline 1. This risk stratification helps to determine prognosis and may impact treatment choice, with high-risk patients being treated more aggressively. While other factors like age, performance status, renal function, and extramedullary disease may influence risk assessment, the R-ISS remains the primary framework for risk classification. The 2020 Blood Cancer Journal article 1 also highlights the importance of risk stratification in guiding treatment algorithms for multiple myeloma, but the R-ISS as described in the 2019 ASCO and CCO guideline 1 is the most relevant and up-to-date framework for risk classification.
Clinical Application
In clinical practice, the R-ISS should be used to guide treatment decisions and predict outcomes for patients with multiple myeloma. This includes determining the intensity of treatment, with higher-risk patients often requiring more aggressive approaches, such as proteasome inhibitors, immunomodulatory drugs, and consideration for early stem cell transplantation when eligible. By using the R-ISS to inform treatment decisions, clinicians can provide personalized care that takes into account the unique characteristics and prognosis of each patient.
From the Research
Multiple Myeloma Risk Classification
- Multiple myeloma can be classified into several subtypes based on baseline cytogenetics, and prognosis varies according to underlying cytogenetic abnormalities 2.
- The Revised International Staging System (R-ISS) combines markers of tumor burden (albumin, beta-2 microglobulin) with markers of aggressive disease biology (high-risk cytogenetics and elevated serum lactate dehydrogenase) to classify patients into three distinct risk groups: R-ISS I, R-ISS II, and R-ISS III 2, 3.
- The presence of del(17p), t(4;14), t(14;16), t(14;20), gain 1q, or p53 mutation is considered high-risk multiple myeloma, and the presence of any two high-risk factors is considered double-hit myeloma, while three or more high-risk factors is considered triple-hit myeloma 4.
- The R-ISS is a simple and powerful prognostic staging system, and it is recommended for use in future clinical studies to stratify patients with newly diagnosed multiple myeloma effectively with respect to the relative risk to their survival 3.
- The detection of circulating plasma cells at diagnosis may be used as a further prognostic biomarker to improve the risk stratification of patients with multiple myeloma staged as R-ISS II 5.
- The International Staging System (ISS) is a simple, reliable staging system for multiple myeloma that can be applied internationally for patient classification and stratification, and it consists of three stages based on serum beta2-microglobulin and serum albumin levels 6.