Rapid response to single agent daratumumab is associated with improved progression-free survival in relapsed/refractory AL amyloidosis.

Daratumumab is a monoclonal antibody, which targets CD38; an antigen expressed on malignant plasma cells in AL amyloidosis thus providing a rationale for its use. Patients treated with daratumumab monotherapy (2016-2019) for relapsed/refractory systemic AL amyloidosis were identified from the database at the UK National Amyloidosis Centre. Of 50 evaluable patients, haematological responses at 3 months were: CR - 19 (38%), VGPR - 14 (28%), PR - 9 (18%) and no response - 8 (16%). Median time to response was 1 (1-6) month. Of assessable patients, cardiac, renal and hepatic responses were seen in 43.8%, 25.0% and 0% of patients whilst progression occurred in 25.0%, 12.5% and 37.5% respectively. Patients achieving a CR had longer median OS (not reached vs. 22.7 months [95% CI 17.0-28.4 months]) ( = .036). Furthermore, patients achieving a rapid response (at 1 month) had a longer median PFS (not reached vs. 9 months [95% CI 5.8-12.2 months]) ( = .013). Daratumumab monotherapy is effective in multiply-relapsed systemic AL amyloidosis and should be considered, if available, in patients who have not received prior daratumumab therapy. Responses are achieved rapidly and overall response rate was 84%. CR predicts overall survival whilst speed of response is predictive of a longer PFS.