Treatment of Multiple Myeloma: Current Status and a Future Perspective

Abstract

Recent advances in the development of novel agents such as proteasome inhibitors (PI), immunomodulatory drugs (IMiDs), and monoclonal antibodies (mAbs) have dramatically improved the prognosis of the patients with multiple myeloma (MM). Currently, induction therapy with novel agents followed by autologous stem-cell transplantation (ASCT) is the standard of care for transplant-eligible patients with newly diagnosed MM (NDMM). Maintenance therapy using low-dose lenalidomide is a standard of care (SOC) in Western countries, whereas it has not been recognized as a SOC in Japan. For transplant-ineligible patients with NDMM, treatment with novel agents either for the limited period with bortezomib, melphalan and prednisolone (MPB) or as continuous therapy with lenalidomide and dexamethasone (Ld) is the SOC. On the other hand, MM consists of heterogeneous diseases based on chromosomal and molecular alterations. Furthermore, subgroup analyses in large-scale clinical trials have revealed different sensitivities to each novel agent according to subtypes of MM. For instance, long-term use of PIs are particularly effective for MM patients with high-risk cytogenetics.; mAbs in combination with these agents can increase their efficacy. For the patients with standard-risk MM, continuous therapy consisting of an IMiD in combination with mAb seems quite effective resulting in a long-term progression-free survival. In the era of precision medicine, the treatment strategy for each patient needs to be optimized based on the heterogeneity of MM cells. Although the druggable driver gene mutations are rarely found in MM, recent discovery of a Bcl2 family-specific inhibitors could illustrate the stratification of MM subtypes. The patient status such as frailty, complications and organ functions need to be taken into account as an important determinant of the treatment choice in elderly patients. Thus, the stratified or personalized treatment in MM can be developed in the near future.