From the Guidelines
High risk multiple myeloma in the Revised International Staging System (R-ISS) classification is defined as stage III disease, which represents the most advanced and aggressive form of multiple myeloma, characterized by a combination of high-risk features including high serum beta-2 microglobulin, high lactate dehydrogenase (LDH) levels, and the presence of high-risk cytogenetic abnormalities such as del(17p), t(4;14), or t(14;16) detected by fluorescence in situ hybridization (FISH) 1.
Key Features of High-Risk Multiple Myeloma
- High serum beta-2 microglobulin levels
- Elevated lactate dehydrogenase (LDH) levels above the upper limit of normal
- Presence of high-risk cytogenetic abnormalities such as del(17p), t(4;14), or t(14;16) detected by FISH
Prognosis and Treatment
Patients with R-ISS stage III multiple myeloma typically have a poorer prognosis with a 5-year overall survival rate of 40% 1. Treatment for high-risk multiple myeloma generally involves more intensive therapy, often including proteasome inhibitors, immunomodulatory drugs, and dexamethasone, followed by autologous stem cell transplantation for eligible patients. Maintenance therapy is particularly important for these high-risk patients to help control the disease long-term.
Importance of R-ISS Classification
The R-ISS classification helps clinicians stratify patients for appropriate treatment intensity and provides important prognostic information for patients and their families. It is essential to use the most recent and highest quality study, such as the 2019 study published in the Journal of Clinical Oncology 1, to guide treatment decisions and improve patient outcomes.
From the Research
Definition of High-Risk Multiple Myeloma
- High-risk multiple myeloma is defined by the presence of certain cytogenetic abnormalities, including del(17p), t(4;14), t(14;16), t(14;20), gain 1q, or p53 mutation 2, 3, 4, 5, 6.
- The presence of any two high-risk factors is considered double-hit myeloma, and three or more high-risk factors is considered triple-hit myeloma 2, 3, 6.
Cytogenetic Abnormalities
- del(17p) is a high-risk cytogenetic abnormality associated with poor prognosis in multiple myeloma 2, 3, 4, 5.
- t(4;14) is a high-risk cytogenetic abnormality associated with poor prognosis in multiple myeloma 2, 3, 4, 5.
- t(14;16) is a high-risk cytogenetic abnormality associated with poor prognosis in multiple myeloma 2, 3, 4.
- t(14;20) is a high-risk cytogenetic abnormality associated with poor prognosis in multiple myeloma 2.
- Gain 1q is a high-risk cytogenetic abnormality associated with poor prognosis in multiple myeloma 2, 3, 4.
- p53 mutation is a high-risk cytogenetic abnormality associated with poor prognosis in multiple myeloma 2, 3, 6.
Risk Stratification
- The Revised International Staging System (R-ISS) is used to stratify multiple myeloma patients into different risk categories 6.
- The R-ISS incorporates cytogenetic abnormalities, including del(17p), t(4;14), and t(14;16), to define high-risk multiple myeloma 6.
- Experts agree that the definition of high-risk multiple myeloma should be revised to include additional clinical and biological risk factors, such as chromosome 1 abnormality, TP53 mutation or deletion, circulating plasma cells by next generation flow, and extramedullary plasmacytomas 6.