Abstract
The treatment landscape for patients with multiple myeloma (MM) who are ineligible for transplant has evolved significantly over time. Initially dominated by melphalan-based regimens, treatment options have progressed with the introduction of proteasome inhibitors, immunomodulatory drugs, and more recently, anti-CD38 monoclonal antibodies. These advances have led to the development of doublet, triplet, and quadruple regimens, aiming not only for survival benefits, but also for meaningful responses, as represented by minimal residual disease negativity, while maintaining tolerability. The management of frailty in older patients has gained importance, and various frailty assessment tools have been proposed to guide treatment decisions. At the same time, ongoing efforts are being made to develop differentiated treatment strategies for patients with frailty based on frailty status. This review discusses the key therapeutic strategies for patients with MM who are transplant ineligible, the role of frailty assessments, and emerging treatment strategies that promise further evolution in treatment outcomes.