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Novel investigations and treatment outcomes in systemic AL amyloidosis

Manwani, Richa; (2021) Novel investigations and treatment outcomes in systemic AL amyloidosis. Doctoral thesis (M.D(Res)), UCL (University College London). Green open access

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Abstract

Background Systemic AL amyloidosis (AL) is a potentially fatal disorder characterised by fibrillary deposition of monoclonal immunoglobulin light chains within organs. Outcomes in AL have improved, but ~20% of patients die within six months of diagnosis. Aims Since upfront bortezomib-based therapy is the mainstay of contemporary AL management, I aim to assess outcomes with this therapy in a large UK cohort. Within this cohort, I shall explore the impact of achieving a ‘stringent’ light chain response. I also aim to explore outcomes in AL patients with advanced cardiac involvement, and patients who do not achieve early haematological responses to upfront therapy. Few AL patients are eligible for upfront autologous stem cell transplantation (ASCT) due to advanced cardiac involvement, and I shall explore the role of deferred ASCT in initially transplant-ineligible patients. I shall examine treatment outcomes with rituximab-bendamustine in IgM-associated AL. AL patients with severe neuropathic involvement have limited chemotherapeutic options, and I shall assess outcomes with the second-generation proteasome inhibitor, carfilzomib, in such patients. The final aim of this thesis is to perform a pilot study of 18F-florbetapir, a novel imaging tracer, in cardiac AL. Results and conclusion Bortezomib-based therapy results in good overall survival and time-to-next-treatment in AL. A ‘stringent’ light chain response predicts prolonged time-to-next-treatment and excellent organ responses. Patients who do not achieve early haematological responses with bortezomib can still go on to achieve excellent haematological responses. AL patients with advanced cardiac involvement who achieve rapid, deep haematological responses have survival outcomes that are better than previously reported. Deferred ASCT is a potential treatment option in initially transplant-ineligible AL patients. Rituximab-bendamustine induces good haematological responses in IgM-associated AL. Carfilzomib is an effective treatment option in AL patients with significant neuropathic involvement. 18F-florbetapir PET is associated with cardiac uptake in AL patients with cardiac involvement.

Type: Thesis (Doctoral)
Qualification: M.D(Res)
Title: Novel investigations and treatment outcomes in systemic AL amyloidosis
Event: UCL
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Copyright © The Author 2021. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10120831
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