Benefit of daratumumab-based treatment in advanced cardiac stage light chain amyloidosis

Background Advanced cardiac-stage light chain (AL) amyloidosis has a poor prognosis. Other than in early-stage disease, Daratumumab’s role is less well established. Methods In this multi-center, retrospective study we analyzed patients with newly diagnosed AL amyloidosis with cardiac involvement and baseline NT-proBNP of ≥ 1800 ng/l, enrolled in the Swiss Amyloidosis Registry. We compared overall survival (OS), progression-free survival 1 and 2 (PFS), and treatment response in patients receiving Daratumumab as first- or second-line therapy to those who never received Daratumumab. Results Seventy six patients were included, median baseline NT-proBNP was 4’180 ng/l. 25 and 51 patients had 2012 revised Mayo stage III and IV disease. Patients treated with Daratumumab showed significantly higher OS and improved PFS2 compared with those who never received Daratumumab (2y-OS 75.8% vs. 52.2%, log-rank < 0.05, 2y-PFS2 75.4% vs. 58.4%, log-rank: 0.068). No significant difference was observed between patients treated with versus without first-line Daratumumab. Deep hematologic and organ responses (CR/VGPR) were higher in the Daratumumab group and strongly associated with improved survival. Conclusion Daratumumab as part of the first two lines of therapy is associated with superior survival and deeper hematological and organ response in patients with advanced cardiac AL amyloidosis, supporting its broader application.