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

Abstract

Background: 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.Method: Patients treated with daratumumab monotherapy (2016-2019) for relapsed/refractory systemic AL amyloidosis were identified from the database at the UK National Amyloidosis Centre.Results: 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]) (p = .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 = .013).Conclusion: 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.

• Authors: Oliver C Cohen, Maximillian H Brodermann, Iona J Blakeney, Shameem Mahmood, Sajitha Sachchithanantham, Sriram Ravichandran, Steven Law, Helen J Lachmann, Carol J Whelan, Rakesh Popat, Neil Rabin, Kwee Yong, Charalampia Kyriakou, Raakhee Shah, Simon Cheesman, Sarah Worthington, Philip Hawkins, Julian D Gillmore, Ashutosh D Wechalekar
• Journal: Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis (Amyloid) Vol. 27 Issue 3 Pg. 200-205 (Sep 2020) ISSN: 1744-2818 [Electronic] England
• PMID: 32408823 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Antibodies, Monoclonal
• daratumumab
• ADP-ribosyl Cyclase 1

Topics

• ADP-ribosyl Cyclase 1 (genetics)
• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal (administration & dosage, adverse effects)
• Disease-Free Survival
• Female
• Humans
• Immunoglobulin Light-chain Amyloidosis (drug therapy, epidemiology, pathology)
• Male
• Middle Aged
• Plasma Cells (metabolism, pathology)
• Progression-Free Survival
• Treatment Outcome