**4. Management of MM**

Over the past two decades, management of MM has dramatically changed and this has translated into significant improvements in disease outcomes and prognosis. This unprecedented progress can be attributed to (1) the application of high-dose (HD) chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT), (2) improvement in supportive care strategies and (3) the introduction of several novel agents particularly immunomodulatory agents and proteasome inhibitors in the treatment of patients with MM [10, 13, 16, 59–61].

Cytotoxic agents that have been used in the treatment of MM include (1) corticosteroids such as dexamethasone and prednisolone, (2) conventional chemotherapies including melphalan, cyclophosphamide, liposomal doxorubicin, bendamustine, carmustine (BCNU), D-PACE (dexamethasone, cisplatin, doxorubicin, cyclophosphamide, etoposide) and DCEP (dexamethasone, cyclophosphamide, etoposide, cisplatin) [62]. However, remarkable improvements in survival of patients with MM have been achieved following the introduction of thalidomide, bortezomib and lenalidomide, as well as the recent introduction and approval of the following novel therapeutic agents: (1) newer proteasome inhibitors such as carfilzomib and ixazomib; (2) histone deacetylase inhibitors such as panobinostat and vorinostat; (3) new immunomodulatory drugs such as pomalidomide; (4) monoclonal antibodies such as daratumumab and elotuzumab; (5) Bruton tyrosine kinase inhibitors such as ibrutinib; (6) IL-6 inhibitors such as siltuximab; (7) PI-3 K inhibitors and (8) various immunotherapeutic strategies including chimeric antigen receptor (CAR) T cells [10, 13, 15, 62–64].
