Frontline daratumumab, lenalidomide, and dexamethasone in patients older than 80 years with newly diagnosed multiple myeloma: treatment durability, infectious complications, and nutritional vulnerability.

PURPOSE: To evaluate the effectiveness, treatment durability, and infectious complications of frontline daratumumab, lenalidomide, and dexamethasone (DRd) in patients aged > 80 years with transplant-ineligible newly diagnosed multiple myeloma (Ti-NDMM) and to explore associations between baseline nutritional vulnerability and treatment outcomes. METHODS: We retrospectively analyzed consecutive patients aged > 80 years with Ti-NDMM who received frontline DRd. Treatment outcomes and infectious complications were also evaluated. Exploratory analyses were performed according to baseline nutritional indices, including the Prognostic Nutritional Index (PNI) and Geriatric Nutritional Risk Index. RESULTS: Fifteen patients were included. The overall response rate was 93.3%, and 53.3% of patients achieved a very good partial response or better. After a median follow-up of 23.1 months, the estimated median duration of treatment (DOT), time to the next treatment, and progression-free survival (PFS) were 36.7, 44.6, and 40.0 months, respectively, while the estimated median overall survival was not reached. Infectious complications, including two infection-related deaths, represented a major barrier to treatment continuation. Severe infections predominantly occurred within the first year of treatment initiation. In exploratory analyses, patients with a low baseline PNI had a shorter DOT (30.8 months vs. not reached; p = 0.049) and more frequent grade 3-5 infections (71.4% vs. 12.5%; p = 0.041). CONCLUSION: Frontline DRd demonstrated favorable effectiveness and clinically meaningful treatment durability in patients aged > 80 years with Ti-NDMM. Infectious complications, particularly during the early treatment period, frequently compromised the continuation of treatment. Exploratory analyses suggested that a lower baseline PNI may be associated with severe infectious complications and a shorter treatment durability.