Improved survival with daratumumab-CyBorD compared with CyBorD as frontline therapy for AL amyloidosis

• The addition of daratumumab to CyBorD significantly improves hematological and organ response • Daratumumab-CyBorD frontline therapy improves survival and reduces early death in AL amyloidosis. Light chain (AL) amyloidosis is a life-threatening plasma cell dyscrasia. In the Andromeda phase III trial, the addition of daratumumab to cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) as front-line therapy significantly improved hematological and organ responses, and event-free survival (EFS) compared to CyBorD. We performed a retrospective study of 361 consecutive newly diagnosed AL amyloidosis patients treated at our institution between 2018 and 2022. Patients who received Dara-CyBorD (n=147) were compared to those treated with CyBorD (n=214) in key outcomes endpoints. The hematological very good partial response or better rate at 2-month was higher in Dara-CyBorD compared to CyBorD (60.8% vs 31.3%, P<0.001). In addition, hematological complete response at 2-month and 6-month was higher with Dara-CyBorD compared to CyBorD (15.3% vs 3.0%; 39.5% vs 17.8%; both P<0.001). Fewer Dara-CyBorD patients required second-line therapy at the 12-month landmark compared to CyBorD (14.9% vs 42.9%, P<0.001). Cardiac responses at 6-month and 12-month were higher and deeper in the Dara-CyBorD group compared to CyBorD. Treatment with Dara-CyBorD was associated with a lower 6-month mortality rate compared to CyBorD (8.8% vs 16.3%, P=0.04). EFS and overall survival (OS) were superior in the Dara-CyBorD group compared to CyBorD. An OS difference between the treatment groups was statistically significant among cardiac stage II, and borderline significant for stage IIIA, but not for cardiac stage IIIB. In conclusion, the addition of daratumumab to frontline CyBorD significantly improved hematological and organ response rates, reduced early deaths, and prolonged EFS and OS compared to CyBorD.