How First-Line Therapy is Changing in non-Transplant Eligible Multiple Myeloma Patients.

Treatment outcomes for patients with multiple myeloma have improved in recent decades thanks to new insights into the biology of the disease and the introduction of new drugs and therapeutic approaches. More than half of patients with multiple myeloma are not eligible for transplantation, and for years, their treatment has been difficult due to the heterogeneity of this patient group and the lack of treatment options. Recently, attention has focused on the concept of frailty and its quantification in order to adapt the schedule and dosage of treatment to the state of fitness. Modulation of therapy for frailty can reduce side effects and toxicity-related death and define the various successes of therapy. The role of frailty and the development of new tools may provide a way forward to customize the treatment of different patients with multiple myeloma who are not eligible for transplantation. The use of the new association, particularly based on monoclonal antibodies against CD38, showed profound and durable results in terms of progression-free survival and overall survival. Today, these combinations, especially daratumumab-lenalidomide and dexamethasone, represent the "gold standard" of treatment for these patients. The latest quadruplet therapies and cell-directed therapies, including bispecific antibodies and chimeric antigen receptor T-cell (CAR-T) treatment, appear to be very effective and achieve a high rate of negative minimal residual disease. These latter approaches could redefine the population over the age of 65 that is now considered transplant-eligible.