Evolution of Treatment Paradigms in Newly Diagnosed Multiple Myeloma

The plasma cell neoplasm multiple myeloma (MM) is currently considered incurable. However, significant advances in treatment options over the past 20 years have led to unprecedented response rates to initial therapy as well as prolonged survival rates. Induction regimens have evolved from alkylator-based therapies to those consisting of immunomodulatory drugs and proteasome inhibitors. The combination of bortezomib/lenalidomide/dexamethasone (VRd) has emerged as a standard regimen for both transplant-eligible (TE) and transplant-ineligible (TI) patient populations. More recent efforts have focused on the incorporation of monoclonal antibody therapy into the newly diagnosed setting, particularly anti-CD38 monoclonal antibodies. In the TI patient population, the combination of daratumumab/lenalidomide/dexamethasone is now considered another standard therapy. In the TE setting, it remains to be determined whether the addition of daratumumab to the VRd backbone results in improved long-term outcomes. Recent studies have confirmed the progression-free survival benefit of upfront autologous stem cell transplant and have established lenalidomide maintenance as a standard of care. Multiple studies are evaluating whether inclusion of monoclonal antibody therapy in the maintenance setting will improve outcomes. The optimal management of newly diagnosed patients with high-risk cytogenetics remains to be determined. We discuss the emerging therapies that will likely shape management of newly diagnosed MM in the future.