Up-Front Treatment of Elderly (Age ≥75 Years) and Frail Patients With Multiple Myeloma.

Older patients with multiple myeloma (MM) exhibit wide heterogeneity in their baseline physiologic and functional status, which demands an individualized treatment approach based on biological rather than chronological age. Various frailty scores have been developed for older patients with MM, but they are underutilized in clinical trials and in practice. Older patients with MM are underrepresented in therapeutic clinical trials, and treatment recommendations are currently derived from clinical trials of transplant-ineligible patients. This article provides a summary of phase II and III clinical trials in transplant-ineligible patients with newly diagnosed MM, highlighting outcomes in patients aged ≥75 years and frailty-based outcomes. The data available thus far show that triplet regimens are more efficacious than doublets in older patients but may be associated with higher toxicity. DRd (daratumumab/lenalidomide/dexamethasone) and VRd (bortezomib/lenalidomide/dexamethasone) are good options in patients who are nonfrail, whereas dose-adjusted DRd and VRd-lite should be offered to frail patients. Frailty should be assessed regularly to guide treatment intensification and/or deescalation. It is important that frailty measures are incorporated in clinical trials evaluating novel treatments to inform how older and frail patients will benefit from these treatments.