Daratumumab therapy in AL amyloidosis with or without multiple myeloma and cardiac response

Background AL amyloidosis and multiple myeloma are plasma cell dyscrasias characterized by excess light-chain production leading to cardiac amyloid deposition and organ dysfunction. While effective, proteasome inhibitor–based therapy and stem cell transplantation are often limited in advanced disease. Daratumumab provides durable and well-tolerated plasma cell suppression and enables assessment of long-term cardiac outcomes. Purpose To evaluate the long-term effects of daratumumab therapy on cardiac biomarkers and myocardial amyloid burden, assessed by artificial intelligence- based electrocardiographic (AI-ECG) and echocardiographic measures, in patients with AL amyloidosis and cardiac involvement. Methods Following IRB approval, we conducted a retrospective review of patients with AL amyloidosis and cardiac involvement treated with daratumumab at Mayo Clinic Rochester since 2015, with a minimum follow-up of 6 months. Demographic, clinical, cardiac biomarker, electrocardiographic, and echocardiographic data were collected at baseline and last follow-up. Paired comparisons were performed using the Wilcoxon signed-rank test. Results Overall, 67 patients with AL amyloidosis were included (mean age at diagnosis 59 ± 10 years; 47 [70%] male; concomitant multiple myeloma 13 (19%) patients, mean left ventricular ejection fraction 61 ± 7%), with a mean follow-up duration of 8.3 ± 5.4 years. At diagnosis, the most common organ involvements were renal and cardiac, affecting 78% and 67% of patients, respectively. Free light-chain isotype was λ in 52 patients (75%) and κ in 17 (25%) and immunoglobulin heavy-chain was identified in 26 patients. Among patients with available baseline staging data, Mayo Clinic revised cardiac staging (2012) classified 32% as stage I, 14% as stage II, 21% as stage III, and 32% as stage IV. Most patients were NYHA class II (62%), with 27% in class III–IV. Baseline creatinine clearance <60 ml/min was observed in 48% of patients. No significant changes were observed in conventional echocardiographic parameters during follow-up. In contrast, cardiac biomarkers improved significantly with high-sensitivity troponin T decreased from a baseline median of 59 [25, 104.5] ng/L to 30.5 [14.5, 58.75] ng/L at follow-up (p = 0.003), and NT-proBNP declined from 1,053 [423.5, 6,211.5] pg/mL to 729 [299, 2,328] pg/mL (p = 0.02). Interestingly, artificial intelligence–based electrocardiographic analysis demonstrated a marked reduction in the predicted likelihood of cardiac amyloidosis, decreasing from 55.8% [5.1, 99.6] at baseline to 19.3% [4.3, 68.4] at follow-up (p < 0.0001). Conclusions Long-term daratumumab therapy was associated with significant reductions in cardiac biomarkers and AI-ECG derived measures of myocardial amyloid burden. These findings support the hypothesis that sustained suppression of pathogenic light-chain production may permit gradual improvement in amyloid cardiomyopathy over time.