Risk Stratification for Multiple Myeloma

Risk Stratification for Multiple Myeloma

Dr. Saad Z. Usmani
In the following article, Saad Z. Usmani, MD, FACP, answers a question posed by an attendee during a 2015 Best of ASCO® Meeting. Dr. Usmani is chief of the Plasma Cell Disorders Program and director of Clinical Research in Hematologic Malignancies at Levine Cancer Institute/Carolinas Healthcare System, and clinical associate professor of medicine at the University of North Carolina School of Medicine, Chapel Hill.

Question: What is the recommended method of risk stratification for multiple myeloma?

Answer: Multiple myeloma (MM) is a biologically heterogeneous group of diseases that present with variable disease burden. Although the median age of diagnosis is 69, one-third of patients with MM are younger than age 65, with infrequent cases diagnosed in late teens or early twenties.

Table 1
Table 2
Current risk-stratification methodologies in MM are prognostic in nature and account for disease burden, high-risk disease features, and host factors. The Durie-Salmon staging system1 and the International Staging System2 (ISS) are perhaps more disease-burden driven, but are critiqued for being based on outdated datasets (pre-novel therapy era).

The International Myeloma Working Group published a risk stratification that combined both disease burden and biology features (Table 1).3 Based on these criteria, a revised ISS (R-ISS) was recently published, and patients were stratified on the basis of high-risk prognostic features (e.g., ISS stage III,2 high serum lactate dehydrogenase, t[4;14], t[14;16], Del17p) into three subgroups with different survival outcomes (Table 2).4 The dataset used for R-ISS included 4,445 patients of whom only 5% had not received any novel agents for upfront treatment, 65% were aged 65 or younger, and 35% were older than age 65 (range 18 to 91 years). Therefore, the stratification is applicable to both transplant-eligible and -ineligible patients with MM.

The R-ISS is now considered the new risk-stratification algorithm that will be used for clinical practice and clinical trial reporting for patients with newly diagnosed MM. Currently, the R-ISS does not account for some high-risk features, such as primary plasma-cell leukemia, extramedullary disease, or the influence of comorbidities in choosing optimal therapy.