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

In the ANDROMEDA phase 3 trial, the addition of daratumumab to cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) as frontline therapy significantly improved hematological and organ responses, and event-free survival (EFS) compared with CyBorD. To validate its results, we performed a retrospective study of 361 consecutive patients with newly diagnosed light chain (AL) amyloidosis treated between 2018 and 2022. Patients who received Dara-CyBorD (n = 147) were compared with those treated with CyBorD (n = 214) in key outcome endpoints. The 2-month hematological very good partial response or better rate was higher with Dara-CyBorD than with CyBorD (60.8% vs 31.1%;  < .001). In addition, 2- and 6-month hematological complete response was also higher with Dara-CyBorD (15.3% vs 3.0% and 39.5% vs 17.8%, respectively; both  < .001). Fewer patients treated with Dara-CyBorD required second-line therapy at the 12-month landmark (14.9% vs 42.9%;  < .001). The 6- and 12-month cardiac responses were higher and deeper in the Dara-CyBorD group than in the CyBorD group. Dara-CyBorD was associated with a lower 6-month mortality rate (8.8% vs 16.3%;  = .04) and superior EFS and overall survival (OS). An OS difference between the treatment groups was statistically significant among patients with stage II cardiac disease, 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 with CyBorD.