Multiple myeloma is a relatively rare form of blood cancer that affects plasma cells, which are immune cells that produce antibodies. In multiple myeloma, these malignant plasma cells increase in number in the bone marrow and crowd out normal blood cells, which produces large quantities of abnormal antibodies in the blood and urine.
Multiple myeloma is very complex and requires physicians to characterize carefully each patient’s disease to determine the best treatment plan. Part of this characterization involves disease staging (determining the extent of the myeloma cells), and determining the patient’s risk status, which is categorized as either standard-risk or high-risk multiple myeloma. Being well informed about your risk status may help you to have quality conversations with your treatment team and may assist your providers in helping you to achieve the best outcome. To understand patients’ awareness of, and experience with, risk status assessment in multiple myeloma, an Internet-based survey was conducted among individuals with multiple myeloma or their caregivers. The complete findings from this survey can be found in the full version of this article.
Survey Fact: 66% of survey respondents would like to know if they have high-risk multiple myeloma.
Determining a patient’s risk status at the time of diagnosis is important, because it provides information on prognosis. Patients with high-risk multiple myeloma tend to respond to therapy for a shorter length of time, have more frequent relapses, and have shorter survival compared with patients with standard-risk multiple myeloma. The goal of treatment is to optimize patient outcomes and quality of life while minimizing short- and long-term side effects, using a risk-adapted approach.
Several factors influence risk and help predict outcomes in multiple myeloma. These factors can be grouped into 3 categories: patient-related factors (things that are related specifically to the patient and their overall health), tumor burden (the amount of cancer in the body), and tumor characteristics or biology (features of the multiple myeloma itself, such as details that may show how aggressive it is or how fast it may grow).
Several laboratory tests can be performed on a patient’s bone marrow to help identify chromosomal abnormalities in myeloma cells and help determine the risk. Two of these, cytogenetic analysis (also known as karyotyping) and fluorescence in situ hybridization (FISH), are used the most often. National treatment guidelines recommend that all patients with multiple myeloma undergo chromosome analysis by FISH for risk assessment at the initial diagnosis, stating that karyotyping may provide additional information.
Survey Fact: 41% of respondents had not heard of these cytogenetic tests. Almost half of the respondents were familiar with FISH, and a third were familiar with karyotyping.
Several guidelines have been developed that define criteria to denote high- and standard-risk multiple myeloma. The most common of these guidelines are the International Myeloma Working Group (IMWG) and Mayo Stratification and Risk-Adapted Therapy (mSMART). However, it is now more common to stratify a patient’s risk of multiple myeloma based on the presence of individual cytogenetic abnormalities. In general, multiple myeloma that does not have any of these cytogenetic abnormalities is referred to as standard-risk disease.
Survey Fact: Only 25% of respondents understand very well what is meant by standard-risk versus high-risk disease.
Although multiple myeloma treatment guidelines recommend that all patients undergo chromosome analysis by FISH for risk assessment, and that other optional tests may provide additional information regarding prognosis and choice of therapy, additional factors during the time an individual receives therapy and beyond may affect their prognosis to the extent that a patient’s risk status may change over time. For this reason, the concept of dynamic risk assessment is evolving as an ongoing way to define risk. For example, one factor that can be used in dynamic risk assessment is the amount of residual (multiple myeloma) disease that is present after treatment. Another factor that contributes to risk is the time between the initial diagnosis and disease relapse.
After the assessment of risk, multiple myeloma treatment can be tailored according to a patient’s genetic abnormalities and other risk factors. As such, different treatment strategies can be used in high-risk multiple myeloma to help improve outcomes. In general, patients with high-risk disease receive more aggressive therapy that may be given continuously or for a longer period of time.
Survey Fact: Only 42% of respondents were aware that individuals with high-risk multiple myeloma may receive different treatment from those with standard-risk disease.
In conclusion, risk assessment is an important step in tailoring therapy and improving outcomes in high-risk multiple myeloma. Research has identified biomarkers in multiple myeloma that can identify patients at high risk of early disease progression and death. Future research will help determine the best combination of treatments for high-risk multiple myeloma that are tolerable, convenient, and can be taken long-term.