Outcomes of patients with systemic light chain amyloidosis treated with DVD front-line therapy.

A substantial proportion of patients are unsuitable candidates for the Dara-CyBorD regimen (daratumumab-cyclophosphamide-bortezomib-dexamethasone), the standard frontline treatment for systemic amyloid light-chain (AL) amyloidosis as established in the ANDROMEDA clinical trial. This is primarily due to their severe organ dysfunction and limited treatment tolerance. In this work, we evaluated an alternative frontline regimen of DVD (daratumumab-bortezomib-dexamethasone) in 64 newly diagnosed patients with AL amyloidosis, including those with advanced cardiac disease. The best hematologic response achieved was a complete response (CR) in 56.3% of patients, with very good partial response (VGPR) or better observed in 68.8%, not inferior to the hematologic responses reported in the ANDROMEDA trial. At 6 months, 13 (48.1%) achieved a cardiac response and 17 (85.0%) achieved a renal response, compared favourably to the data in ANDROMEDA. Notably, the incidence of grade ≥ 3 infections was 1.6%, significantly lower than the 7.8% reported in ANDROMEDA. The estimated 1- and 2-year overall survival (OS) rates were 84.4% and 82.8%, respectively. The profound hematologic response rates (VGPR/CR) in mayo stage IIIB patients were comparable to those in mayo stage I-IIIA patients, while the median OS of stage IIIB patients was significantly shorter than that of stage I-IIIA patients. No therapy-related deaths or permanent treatment discontinuation due to toxicity were observed. Overall, our findings demonstrate that the DVD regimen is both effective and well-tolerated, even in patients with advanced cardiac involvement.