eprintid: 10179018 rev_number: 15 eprint_status: archive userid: 699 dir: disk0/10/17/90/18 datestamp: 2023-10-17 14:57:39 lastmod: 2024-05-23 06:10:08 status_changed: 2023-10-17 14:57:39 type: article metadata_visibility: show sword_depositor: 699 creators_name: Ravichandran, Sriram creators_name: Hall, Andrew creators_name: Jenner, Matthew creators_name: Garg, Mamta creators_name: Kishore, Bhuvan creators_name: Lachmann, Helen creators_name: Gillmore, Julian creators_name: Pitchford, Alexandra creators_name: Oughton, Jamie B creators_name: Mahmood, Shameem creators_name: Sachchithantham, Sajitha creators_name: Hawkins, Philip creators_name: Brown, Sarah creators_name: Wechalekar, Ashutosh title: A phase 1b dose-escalation study of carfilzomib in combination with thalidomide and dexamethasone in patients with relapsed/refractory systemic immunoglobulin light chain amyloidosis ispublished: pub divisions: UCL divisions: B02 divisions: C10 divisions: D17 divisions: G90 keywords: AL Amyloidosis, Carfilzomib, KTD note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. 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 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. date: 2023-05-22 date_type: published publisher: Informa UK Limited official_url: https://doi.org/10.1080/13506129.2023.2169124 oa_status: green full_text_type: other language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 2026241 doi: 10.1080/13506129.2023.2169124 medium: Print-Electronic lyricists_name: Gillmore, Julian lyricists_name: Wechalekar, Ashutosh lyricists_name: Lachmann, Helen lyricists_name: Hawkins, Philip lyricists_id: JGILL78 lyricists_id: AWECH53 lyricists_id: HJLAC80 lyricists_id: PNHAW77 actors_name: Gillmore, Julian actors_name: Berkeley, Jean actors_id: JGILL78 actors_id: JBERK64 actors_role: owner actors_role: impersonator funding_acknowledgements: [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] full_text_status: public publication: Amyloid volume: 30 number: 3 pagerange: 1-7 event_location: England citation: Ravichandran, Sriram; Hall, Andrew; Jenner, Matthew; Garg, Mamta; Kishore, Bhuvan; Lachmann, Helen; Gillmore, Julian; ... Wechalekar, Ashutosh; + view all <#> Ravichandran, Sriram; Hall, Andrew; Jenner, Matthew; Garg, Mamta; Kishore, Bhuvan; Lachmann, Helen; Gillmore, Julian; Pitchford, Alexandra; Oughton, Jamie B; Mahmood, Shameem; Sachchithantham, Sajitha; Hawkins, Philip; Brown, Sarah; Wechalekar, Ashutosh; - view fewer <#> (2023) A phase 1b dose-escalation study of carfilzomib in combination with thalidomide and dexamethasone in patients with relapsed/refractory systemic immunoglobulin light chain amyloidosis. Amyloid , 30 (3) pp. 1-7. 10.1080/13506129.2023.2169124 <https://doi.org/10.1080/13506129.2023.2169124>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10179018/1/Gillmore_Article_File_Clean.pdf document_url: https://discovery.ucl.ac.uk/id/eprint/10179018/2/Gillmore_Supplementary%20appendix.pdf