A phase 1b dose-escalation study of carfilzomib in combination with thalidomide and dexamethasone in patients with relapsed/refractory systemic immunoglobulin light chain amyloidosis

Abstract

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 1^st three cycles. One patient experienced dose-limiting toxicity (acute kidney injury) at a dose of 45 mg/m^2, 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.

Keywords:

• AL Amyloidosis
• Carfilzomib
• KTD

Author contribution

SR, AH, AP, JB and SB analysed the data and wrote the manuscript. MJ, MG, BK, HL, JG, and PH reviewed and approved the manuscript. AW supervised the study, reviewed, and approved the manuscript.

Disclosure statement

ADW has received honoraria from Janssen, GSK, Celgene, and Takeda. The other authors do not have any conflict of interest to disclose.

Additional information

Funding

The funder, Amgen, conducted an independent review of the study protocol but were not involved in the design, conduct, analysis or interpretation and provided study drug free of charge.