Abstract
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.