Treatment of transplant-ineligible newly diagnosed multiple myeloma: advances and future outlook

Abstract

Multiple myeloma (MM) is a hematologic malignancy that primarily affects older adults. The advent of novel agents has improved treatment outcomes, even in elderly patients who are ineligible for autologous stem cell transplantation. In this population, both tumor-related factors (e.g., high-risk cytogenetic abnormalities) and host-related factors (e.g., frailty) are critical for predicting treatment outcomes and adverse events. Standard first-line therapies, including daratumumab (D)-based regimens (D-melphalan, bortezomib, and prednisolone, and D-lenalidomide and dexamethasone), have demonstrated significant survival benefits in phase III trials. Moreover, quadruplet therapy incorporating isatuximab has shown superiority over bortezomib, lenalidomide, and dexamethasone therapy in a recent phase III trial including relatively fit individuals. Emerging immunotherapies, including bispecific antibodies and chimeric antigen receptor-T cells targeting B-cell maturation antigen, have shown efficacy in relapsed/refractory MM. These agents are now being investigated as frontline treatments for transplant-ineligible patients and may become future standards of care. Furthermore, personalized treatment approaches that integrate clinical and biological factors—including depth of response, frailty status, and genetic alterations—are currently under development. Such approaches may facilitate the development of individualized therapies for this vulnerable population.