• Sriram Ravichandran, Andrew Hall, Matthew Jenner, Mamta Garg, Bhuvan Kishore, Helen Lachmann, Julian Gillmore, Alexandra Pitchford, Jamie B Oughton, Shameem Mahmood, Sajitha Sachchithantham, Philip Hawkins, Sarah Brown, and Ashutosh Wechalekar.
• National Amyloidosis Centre, Royal Free Campus, University College London, London, UK.
• Amyloid. 2023 Sep 1; 30 (3): 290296290-296.

IntroductionProteasome 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.ResultsThe 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%.ConclusionCarfilzomib 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.

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