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

Abstract

BackgroundDaratumumab is a monoclonal antibody, which targets CD38; an antigen expressed on malignant plasma cells in AL amyloidosis thus providing a rationale for its use. MethodPatients treated with daratumumab monotherapy (2016)(2017)(2018)(2019) for relapsed / refractory systemic AL amyloidosis were identified from the database at the UK National Amyloidosis Centre. ResultsOf 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]) (p=0.036). 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]) (p=0.013). ConclusionDaratumumab 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.

Immunoglobulin light chain amyloidosis diagnosis and treatment algorithm 2021

“…Early reports suggested a high response rate (76%) in heavily pretreated patients 78 . These data were confirmed by a number of other retrospective studies 79 – 81 . Two prospective phase II studies of daratumumab in combination with dexamethasone for relapsed AL amyloidosis have been with encouraging results.…”

Daratumumab in AL Amyloidosis: A Real-Life Experience of the “RTM” (Regional Tuscan Myeloma Network)

“…In the phase 3 ANDROMEDA trial, subcutaneous daratumumab plus bortezomib, cyclophosphamide, and dexamethasone showed efficacy and safety in newly diagnosed AL amyloidosis [ 16 , 17 ]. Dara-containing regimens also appeared to be highly active in patients with relapsed/refractory AL amyloidosis, providing rapid hematological responses with a good safety profile [ 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ]. Although different studies have been reported in the literature, most are case reports, and real-life clinical studies are needed to confirm the efficacy and toxicities of Dara therapeutic regimens.…”

Worldwide Perspectives of Amyloidosis

“…Milani and Palladini [7] supplies us with a very well-organized review on the value of conventional therapy in amyloidosis. The readers will also enjoy the review of Van Doren and Lentzsch [8], which leads us through nonchemotherapy treatments of amyloidosis and presents data on the current standard of care, VCd, as well as emerging evidence of the important role of daratumumab [9][10][11][12], which may define the new standard of care [13]. Sanchorawala [14], who arguably have the world's greatest experience, provide a comprehensive review about the timing and role of autologous stem cell transplantation in amyloidosis, as well as selection criteria.…”