From the Guidelines
Multiple myeloma is classified into high-risk and low-risk categories based on the presence of specific genetic abnormalities, with high-risk disease defined by the presence of t(4;14), t(14;16), t(14;20), gain 1q, del(17p), or p53 mutation, as stated in the most recent study 1.
Key Factors in Risk Stratification
The classification of multiple myeloma into high-risk and low-risk categories is crucial for determining the prognosis and guiding treatment intensity. The key factors in risk stratification include:
- Cytogenetic abnormalities, such as translocations and deletions
- Serum lactate dehydrogenase (LDH) levels
- Plasma cell proliferation rate
- Extramedullary disease
- Renal failure at diagnosis
High-Risk Multiple Myeloma
High-risk multiple myeloma is characterized by the presence of specific genetic abnormalities, including:
- Deletion of chromosome 17p (del(17p))
- Translocation between chromosomes 4 and 14 (t(4;14))
- Translocation between chromosomes 14 and 16 (t(14;16))
- Translocation between chromosomes 14 and 20 (t(14;20))
- Gain 1q
- p53 mutation These abnormalities are associated with poorer outcomes and shorter survival, as noted in the study 1.
Low-Risk Multiple Myeloma
Low-risk multiple myeloma, on the other hand, lacks these high-risk cytogenetic abnormalities and may include favorable genetic features, such as:
- Hyperdiploidy
- Translocation t(11;14) The International Staging System (ISS) and its revised version (R-ISS) are commonly used for risk stratification, incorporating serum albumin, beta-2 microglobulin levels, and cytogenetic abnormalities, as discussed in the study 1.
Importance of Risk Stratification
Risk stratification is essential in multiple myeloma, as it guides treatment intensity and helps determine the prognosis. High-risk patients often require more aggressive therapy approaches, including proteasome inhibitors, immunomodulatory drugs, and consideration for early stem cell transplantation when eligible, as stated in the study 1.
From the Research
Classification of Multiple Myeloma into High-Risk and Low-Risk Categories
- Multiple myeloma can be classified into high-risk and low-risk categories based on various prognostic tools, including the Revised International Staging System (R-ISS) 2.
- The R-ISS stratifies patients according to serum markers (i.e., albumin, β2-microglobulin, lactate dehydrogenase) and high-risk cytogenetic abnormalities detected by fluorescence in situ hybridization (FISH) 2.
- Cytogenetic abnormalities such as t(4;14), t(14;16), or del(17p) are associated with poor prognosis in multiple myeloma and are considered high-risk features 3, 4.
- The International Staging System (ISS) can be combined with gene expression classifiers, such as EMC92 and UAMS70, to identify novel risk classifications and predict overall survival 5.
- Additional chromosomal changes, such as del(1p32) and del(22q), can also impact the outcome of patients with high-risk cytogenetic abnormalities 4.
Prognostic Factors and Risk Stratification
- Prognostic factors, including clinical, biochemical, imaging, genetic, and dynamic features, can be used to identify patients with high-risk multiple myeloma 6.
- Risk stratification tools, such as the R-ISS and ISS, can help identify patients with high-risk and low-risk disease, but a universally accepted definition of high-risk multiple myeloma remains absent 6.
- Emerging evidence supports the need for refined definitions and more targeted strategies to improve the management of high-risk multiple myeloma 6.
- Measurable residual disease (MRD) analysis can also be used to monitor response and predict outcomes in patients with multiple myeloma 2.