Real-world outcomes of daratumumab in light-chain amyloidosis patients with advanced renal failure: A TriNetX network study.

e19517 Background: Light-chain (AL) amyloidosis frequently involves the renal and cardiac systems and is associated with high mortality and morbidity, particularly in patients with advanced renal dysfunction. Daratumumab is now the standard therapy for the treatment of AL-amyloidosis, and the data on the real-world use of daratumumab in this high-risk population remain limited. Methods: We conducted a retrospective cohort study using the TriNetX global research network. Adults (≥18 years) with AL amyloidosis and advanced renal disease (chronic kidney disease stage 4–5, end-stage renal disease, or dialysis dependence) diagnosed between January 1, 2020, and December 31, 2025, were included. Outcomes in patients treated with daratumumab were compared with those not receiving daratumumab. Propensity score matching (1:1) was performed to balance baseline characteristics, which were assessed 365 days prior to the index date. Clinical outcomes included all-cause mortality, cardiomyopathy, heart failure, atrial fibrillation, and neuropathy. Laboratory outcomes included hematologic abnormalities. Survival was assessed using Kaplan–Meier analysis and Cox proportional hazards models. Results: After propensity score matching, 179 patients were included in each cohort, with a median follow-up of 365 days. All-cause mortality occurred more frequently in the daratumumab cohort (21.2% vs 8.9%), with a hazard ratio for mortality of 2.60 (95% CI, 1.45–4.67; p = 0.001). Daratumumab-treated patients demonstrated lower risks of cardiomyopathy (11.2% vs 17.9%, RR 0.625), heart failure (31.3% vs 45.3%, RR 0.691, p=0.007), and atrial fibrillation (25.1% vs 36.3%, RR 0.692, p = 0.022), while neuropathy (26.3% vs 11.2%, RR 2.35, p<0.0001) was more commonly observed. Daratumumab exposure was associated with a significantly higher incidence of laboratory abnormalities compared with non-daratumumab therapy, with a median follow-up of 180 days. Patients receiving daratumumab had significantly increased risks of anemia (21.8% vs 7.3%; risk ratio RR 3.00, p<0.0001), thrombocytopenia (42.5% vs 9.5%; RR 4.47, p<0.0001), leukopenia (55.9% vs 13.4%; RR 4.17, p<0.0001), neutropenia (34.1% vs 5.6%; RR 6.10, p<0.0001), and lymphopenia (41.9% vs 8.4%; RR 5.00) (all p<0.001). No significant differences were observed in NT-proBNP levels (14.5% vs 16.2%) or proteinuria (8.9% vs 6.1%). Conclusions: In this real-world analysis of AL amyloidosis patients with advanced renal dysfunction, daratumumab exposure was associated with differences in survival and cardiac outcomes, as well as an increased burden of hematologic abnormalities. These findings highlight the need for careful patient selection and close monitoring and support further prospective evaluation of daratumumab in renally impaired AL amyloidosis populations.