Daratumumab for systemic AL amyloidosis: prognostic factors and adverse outcome with nephrotic range albuminuria

Daratumumab has shown promising first results in systemic light-chain amyloidosis (AL). We analyzed a consecutive series of 168 patients with advanced AL receiving either daratumumab/dexamethasone (DD, n=106) or daratumumab/bortezomib/dexamethasone (DVD, n=62). DD achieved a remission rate (RR) of 64% and a very good hematologic remission (VGHR) rate of 48% after three months. Median hematologic event-free survival (hemEFS) was 11.8 months and median overall survival (OS) was 25.6 months. DVD achieved a 66% RR and a 55% VGHR rate. Median hemEFS was 19.1 months and median OS had not been reached. Cardiac organ responses were noted in 22% with DD and 26% with DVD after six months. Infectious complications were common (CTC grade 3/4: DD 16%, DVD 18%) and likely related to a high rate of lymphocytopenia (CTC grade 3/4: DD 20%, DVD 17%). On univariable analysis, hyperdiploidy and gain 1q21 conferred an adverse factor for OS and hemEFS with DD, whereas translocation t(11;14) was associated with a better hemEFS. NT-ProBNP >8500ng/l could not be overcome for survival with each regimen. Multivariable Cox regression analysis revealed dFLC >180mg/l as an overall strong negative prognostic factor. Additionally, nephrotic range albuminuria with an albumin-to-creatinine-ratio (ACR) >220mg/mmol was a significantly adverse factor for hemEFS (Hazard ratio 2,1 and 3,1) with DD and DVD. Daratumumab salvage therapy produced good results and remission rates challenging any therapy in advanced AL. Outcome is adversely influenced by the activity of the underlying plasma cell dyscrasia (dFLC) and nephrotic range albuminuria (ACR).