Systemic light chain (AL) amyloidosis is an incurable disorder caused by extra-cellular deposition of light-chain aggregates in critical organs. An immunomodulatory agent-based quadruplet including anti-CD38 therapy has not been investigated as a first-line treatment in AL amyloidosis. We report the UK experience of daratumumab-bortezomib-thalidomide-dexamethasone for the first-line treatment of AL amyloidosis. Consecutive patients with a new diagnosis of systemic AL between 2021 and 2023 were retrospectively reviewed from the UK National Amyloidosis Centre database. One hundred and two patients were included
median age was 61 years, involved free light-chain concentration 234 mg/L, 65% had cardiac and 63% renal involvement with modified Mayo stage I/II/IIIa/IIIb in 24%/36%/21% and 19% respectively. A median of 6 cycles was delivered. By intention-to-treat analysis, best haematological overall response rate was 97%: complete response at 65%, very good partial response at 22%, partial response at 11% and no response at 3%. At 6- and 12-month time points from treatment initiation, best cardiac response rates were 39% and 45%, respectively, for evaluable patients. At a median duration of 18 months follow-up, the estimated 1-year overall survival was 89% (95% confidence interval [CI] 81-94) and treatment-free survival/death was 82% (95% CI 73-89). We demonstrate efficacy in this real-world population with comparable results to the gold standard, daratumumab-bortezomib-cyclophosphamide-dexamethasone.