A prospective phase 2 trial of daratumumab in patients with previously treated systemic light-chain amyloidosis

Daratumumab is a human monoclonal antibody targeting CD38, an antigen uniformly expressed by plasma cells in multiple myeloma and light-chain amyloidosis (AL). We report the results of a prospective multicenter phase 2 study of daratumumab monotherapy in AL (NCT02816476). Forty previously treated AL patients with a difference between involved and uninvolved free light chains (dFLC) >50 mg/L were included in 15 centers between September of 2016 and April of 2018. Patients received 6 28-day cycles of IV daratumumab, every week for cycles 1 and 2 and every 2 weeks for cycles 3 through 6. Median age was 69 years (range, 45-83). Twenty-six patients had ≥2 organs involved, with heart in 24 and kidney in 26. Median time from diagnosis to enrollment was 23 months (interquartile range, 4-122), with a median of 3 prior therapies (range, 1-5). At data cutoff (September of 2019), all patients discontinued therapy; 33 received the planned 6 cycles. Overall, 22 patients had hematological response, and 19 patients (47.5%) achieved very good partial response (dFLC