TY  - JOUR
SP  - 1
VL  - 30
IS  - 3
N1  - This version is the author accepted manuscript. For information on re-use, please refer to the publisher?s terms and conditions.
UR  - https://doi.org/10.1080/13506129.2023.2169124
JF  - Amyloid
A1  - Ravichandran, Sriram
A1  - Hall, Andrew
A1  - Jenner, Matthew
A1  - Garg, Mamta
A1  - Kishore, Bhuvan
A1  - Lachmann, Helen
A1  - Gillmore, Julian
A1  - Pitchford, Alexandra
A1  - Oughton, Jamie B
A1  - Mahmood, Shameem
A1  - Sachchithantham, Sajitha
A1  - Hawkins, Philip
A1  - Brown, Sarah
A1  - Wechalekar, Ashutosh
TI  - A phase 1b dose-escalation study of carfilzomib in combination with thalidomide and dexamethasone in patients with relapsed/refractory systemic immunoglobulin light chain amyloidosis
AV  - public
Y1  - 2023/05/22/
EP  - 7
N2  - INTRODUCTION: Proteasome inhibitors are the backbone of AL amyloidosis treatment - bortezomib being most widely used. Carfilzomib is a proteasome inhibitor licenced to treat multiple myeloma; autonomic and peripheral neuropathy are uncommon toxicities with carfilzomib. There is limited data on the use of carfilzomib in AL amyloidosis. Here, we report the results of a phase Ib dose-escalation study of Carfilzomib-Thalidomide-Dexamethasone (KTD) in relapsed/refractory AL amyloidosis. RESULTS: The trial registered 11 patients from 6 UK centres from September 2017 to January 2019; 10 patients received at least one dose of trial treatment. 80 adverse events were reported from 10 patients in the 1st three cycles. One patient experienced dose-limiting toxicity (acute kidney injury) at a dose of 45?mg/m2, and another patient had a SAR (fever). Five patients experienced an AE???grade 3. There were no haematologic, infectious, or cardiac AE???grade 3. The overall haematological response rate (ORR) at the end of three cycles of treatment was 60%. CONCLUSION: Carfilzomib 45?mg/m2 weekly can be safely given with thalidomide and dexamethasone. The efficacy and tolerability profile appears comparable to other agents in relapsed AL amyloidosis. These data provide a framework for further studies of carfilzomib combinations in AL amyloidosis.
ID  - discovery10179018
PB  - Informa UK Limited
KW  - AL Amyloidosis
KW  -  Carfilzomib
KW  -  KTD
ER  -