Evolving Strategies in the Initial Treatment of Multiple Myeloma

Until the advents of novel agents, partial response (PR) or better was the established gold standard to initial therapy of multiple myeloma (MM), and treatment goals were focused on relieving symptoms, prevention of organ damage, and modest improvements in survival. With the introduction of autologous stem cell transplant (ASCT), deeper responses, including complete responses (CRs) were more frequent, and contributed to longer survival. In the era of novel therapies, ASCT remains commonly used and its impact on outcome appears superior, albeit less so than when compared with conventional therapy, and its survival benefit is yet to be established in either setting. In addition, in non-transplant candidates, novel therapies have now significantly improved the overall response rates, depth of response, and clinical benefit, to the levels previously only observed with ASCT, which now increasingly challenges the role and timing of ASCT in eligible patients. Nevertheless, the two approaches of treatment, transplant or no transplant, remain commonly accepted. With an improvement in the tolerability of newer regimens and the deferral of ASCT in transplant candidates, the debate has emerged whether the two-pathway approach to the treatment of newly diagnosed myeloma should be re-evaluated. At the same time, treatment goals are also shifting. Many believe that MM can be converted into a chronic disease and that a functional cure maybe a realistic goal, for at least a proportion of patients. This contribution will review these points of discussion and the evolving approach to treatment of newly diagnosed MM.