Risk Stratification and Targets in Multiple Myeloma: From Genomics to the Bedside

Multiple myeloma is a heterogeneous disease. From a clinical point of view, patients have a highly variable outcome, with survival ranging from a few weeks to more than 15 years, or even cure, especially in transplant-eligible patients.1 For a long time, treatment strategies did not take into account this survival heterogeneity, which could be predicted on the basis of several prognostic parameters. The main reason was the availability of drugs. However, recently, the demonstration that some combinations may lead to different outcomes, both in high-risk and standard-risk patients, is changing this paradigm.2-4 What are the most important prognostic factors in MM, and how do they predict outcome? MM is probably the cancer for which the most prognostic parameters have been described. They can be categorized into three groups: (1) related to patients, (2) related to disease burden, and (3) related to the malignant clone itself. In the first category, age is probably the most important; it defines the treatment strategy available for these patients, mostly the feasibility of transplant.1 The age cutoff is usually fixed between ages 65 to 70, depending on the patient’s fitness. Another important factor in this category is the presence or lack of comorbidities, which could prevent the use of some drugs. In the second category (tumor burden), several parameters have been described, such as β2-microglobulin level,5 serum lactate dehydrogenase level,6 anemia,7 thrombocytopenia,7 and several circulating factors (such as CD138 and GDF15).8 The International Staging System9 is based on β2-microglobulin and albumin; the latter reflects several parameters related to the patient’s conditions. Finally, the third category concerns several factors related to the clone biology, such as genetic abnormalities, proliferation index,10 and the monoclonal protein structure that could lead to renal precipitation or amyloidosis deposit. GENETIC ABNORMALITIES Section: ChooseTop of pageAbstractGENETIC ABNORMALITIES <