Efficacy and Safety of Low-Frequency Daratumumab Regimen in Systemic Light-Chain Amyloidosis

In recent years, daratumumab has been increasingly applied in the treatment of systemic light-chain (AL) amyloidosis, significantly improving the prognosis of patients. Currently, the internationally recognized daratumumab treatment regimen comes from the ANDROMEDA trial. Given the low tumor burden and poor tolerance of patients with amyloidosis, in this study, we modified the ANDROMEDA-based protocol by administering daratumumab at half the original frequency. We enrolled 48 patients with AL amyloidosis who received low-frequency daratumumab in multiple hospitals from July 2021 to May 2024 (ChiCTR2100049253). Among these patients, 38 were newly diagnosed and 10 were relapsed and refractory patients. At 3 months, the percentage of newly diagnosed patients with hematologic response≥very good partial response (VGPR) was 75.8%, including 36.4% complete response (CR) and 39.4% VGPR, with an overall response rate (ORR) of 90.9%. The CR, VGPR and ORR rates of relapsed and refractory patients at 3 months were 40.0%, 20.0% and 90.0%, respectively. By 6 months, ≥VGPR was achieved by 86.7% of newly diagnosed patients, while CR, VGPR, and ORR in relapsed and refractory patients were 44.4%, 22.2%, and 77.8%. The 6-month cardiac and renal response rates were 61.9% and 46.2% in newly diagnosed patients, 20.0% and 50.0% in relapsed and refractory patients, respectively. The median follow-up time was 26.0 months. The 1-year and 2-year OS rates were both 89.5% for newly diagnosed patients, and 90.0% for relapsed and refractory patients. Of the 48 patients, 33 (68.8%) received maintenance therapy and 15 (31.3%) did not. The 1-year and 2-year OS rates were both 100.0% for patients receiving maintenance, and 66.7% for patients without maintenance. Considering the safety endpoints, 86.8% of newly diagnosed patients experienced at least one adverse event (AE). In conclusion, the low-frequency daratumumab regimen can be considered as an effective, safe and feasible treatment strategy for AL amyloidosis.