Tailoring Therapy for Frail and Elderly Myeloma Patients

Multiple myeloma is a plasma cell malignancy associated with heterogeneous clinical outcomes. The majority of patients are diagnosed during their seventh decade and often present with age-related comorbidities and organ dysfunction. Myeloma therapeutic landscape is rapidly evolving with the introduction of immune-based therapies, including monoclonal and bispecific antibodies and chimeric antigen receptor (CAR) T-cell therapies targeting CD38, BCMA, and GPRC5D. These novel therapies have led to deeper and more durable responses and have raised the possibility of functional or definitive cure. However, older and frail patients continue to experience poorer outcomes, higher toxicity rates, and substantial treatment attrition, representing a major unmet clinical challenge. In this review, we discuss current approaches to the assessment and management of frailty in patients with multiple myeloma, with a focus on optimizing frontline therapy and treatment at relapse in the era of the possible achievement of a cure. We highlight emerging data on cellular therapies in this population and the importance of individualized, goal-directed treatment strategies aimed at balancing efficacy, tolerability, and quality of life.