1. Rapid response to single agent daratumumab is associated with improved progression-free survival in relapsed/refractory AL amyloidosis
- Author
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Neil Rabin, Iona J Blakeney, Julian D. Gillmore, Oliver C Cohen, Sajitha Sachchithanantham, Simon Cheesman, Raakhee Shah, Sriram Ravichandran, Kwee Yong, Carol J. Whelan, Rakesh Popat, Helen J. Lachmann, Ashutosh D. Wechalekar, Steven Law, Maximillian H Brodermann, Charalampia Kyriakou, Shameem Mahmood, Philip N. Hawkins, and Sarah Worthington
- Subjects
Adult ,Male ,medicine.medical_specialty ,Plasma Cells ,030204 cardiovascular system & hematology ,Gastroenterology ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Refractory ,Antigen ,Internal medicine ,Internal Medicine ,AL amyloidosis ,Humans ,Medicine ,Immunoglobulin Light-chain Amyloidosis ,Progression-free survival ,Rapid response ,Aged ,Aged, 80 and over ,business.industry ,Amyloidosis ,Antibodies, Monoclonal ,Daratumumab ,Middle Aged ,medicine.disease ,ADP-ribosyl Cyclase 1 ,Progression-Free Survival ,Treatment Outcome ,Relapsed refractory ,Female ,business ,030217 neurology & neurosurgery - 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.
- Published
- 2020
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