Risk Stratification in Multiple Myeloma

Multiple myeloma (MM) is a malignant plasma cell disorder, characterized by bone marrow infiltration with clonal plasma cells (PCs), and affects nearly 20,000 patients in United States (US) each year. Revised International Myeloma Working Group (IMWG) diagnostic criteria for MM has included biomarkers, namely, clonal bone marrow PCs = 60%, serum free light chain ratio = 100 and = 1 focal lesion on magnetic resonance imaging (MRI) in addition to traditional CRAB (Hypercalcemia, Renal insufficiency, Anemia and Bone lesions) for defining MM. In the era of risk-adapted therapy with novel agents, importance of comprehensive risk stratification models, including a conglomerate of host factors, tumor factors and factors arising due to host-tumor interaction, is paramount. In this review, we have discussed host factors, including patient demographics and performance status, tumor factors including, albumin, C-reactive protein, lactate dehydrogenase, serum free light chain assay, complete blood count, bone marrow morphology, cytogenetics, gene expression profiling, immunophenotyping and proliferative capacity and factors related to tumor-host interaction, including β-2 microglobulin and renal function, which are important components of risk stratification. Furthermore, response to therapy, including impact of complete remission, early relapse and minimal residual disease after therapy have been shown to predict survival in MM. Clinical application of these components have been reflected in novel risk stratification models, including Mayo stratification of myeloma and risk adapted therapy (mSMART), IMWG and Intergroupe Francophone du Myélome (IFM), with further studies on identifying molecular characteristics of PCs in MM currently underway.