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The last decade’s progress in the treatment of newly diagnosed multiple myeloma has relied on the synergistic combination of agents with different mechanisms of action, basically proteasome inhibitors, immunomodulatory agents, and monoclonal antibodies, in order to achieve the deepest possible response early in the course of treatment. Following induction, several therapeutic strategies aim to improve and maintain response. The manuscript reviews available data for the treatment of newly diagnosed multiple myeloma patients with a focus on most recent induction and maintenance combinations and the still important role of autologous stem transplantation. Future perspectives in the light of initial results from ongoing clinical trials are also addressed. Remarkable progress has been made in myeloma treatment due to the integration of immunomodulators, proteasome inhibitors, monoclonal antibodies, and high dose therapy in the frontline setting. Upfront therapy may be further improved intensifying induction combinations, adapting high dose therapy and consolidation strategies to the patient’s profile, improving maintenance in high-risk individuals, or limiting maintenance duration in those with a better prognosis. Evidence needs to be reviewed, taking into account the therapeutic objectives at each treatment stage and patient specific risk factors.

First-line treatment of multiple myeloma in both transplant and non-transplant candidates