Cook, Gordon ORCID: https://orcid.org/0000-0003-1717-0412 (2023) The role of salvage autologous stem cell transplantation (sASCT) in relapsed multiple myeloma (MM). DSc thesis, University of Leeds.
Abstract
The use of high dose chemotherapy and autologous stem cell transplantation (ASCT) is standard of care first-line therapy for multiple myeloma (MM) in suitably fit patients. In the relapse setting after a prior ASCT, the use of a second or salvage ASCT (sASCT) evolved without randomised controlled trial evidence of clinical effectiveness, largely based on evidence from retrospective registry or single centre studies, and without the incorporation of novel agents in the re-induction phase. Thus, the application of sASCT in the modern clinical era lacked an acceptable evidence base. After a thorough exploration of the unmet need in this area of clinical practice, I designed the first retrospective national, case-matched control analysis on patients who underwent sASCT compared with conventional chemotherapy, and found improved progression-free and overall survival compared with conventional chemotherapy. However, there was a clear unmet need to define the utility of sASCT in the era of novel agents. This required prospective, randomised, multi-centre data that could evidence the clinical effectiveness and quality of life impact. To address this clinical uncertainty, I designed, led and delivered the NCRI-badged UK Myeloma Forum Myeloma X study, funded by Cancer Research UK. This multi-centre, phase III study investigated the role of sASCT as management of first relapsed disease in patients relapsing after a standard first-line ASCT, versus a non-ASCT consolidation, which was standard of care at the time of study set-up and initiation. All patients received a modern-day re-induction regimen for the era of the trial and the trial outcomes sought to influence clinical practice. Additionally, the study explored whether stem cells could be harvested after a prior ASCT, which would otherwise limit the adoption of sASCT in real-world practice. The trial (Myeloma X) provided the first and only global clinical evidence for the benefits of sASCT for relapse MM. In addition, the study defined that the advantages demonstrated by sASCT did not compromise quality of life. Consequentially, sASCT was adopted in national and international guidelines, accepted for reimbursement and has been pivotal to formulating the clinical practice internationally.
The outputs have resulted in a measurable change in clinical practice and it is estimated that over 100 patients a year in the US have benefitted from this treatment as a consequence of the published trial outcomes, with similar benefits having been reported in France and other European countries. Taken together, the results of this trial have had an impact on the clinical management pathway in MM and helping the decision-making process for both physicians and myeloma patients.
The evidence presented in this thesis represents peer-reviewed publications derived from this late phase, practice-changing clinical trial.
Metadata
Supervisors: | NA, NAGordon |
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Keywords: | myeloma, salvage, stem cell transplant, relapse |
Awarding institution: | University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) |
Academic unit: | Leeds Institute of Clinical Trial Research |
Depositing User: | Prof Gordon Cook |
Date Deposited: | 02 Aug 2024 14:01 |
Last Modified: | 02 Aug 2024 14:01 |
Open Archives Initiative ID (OAI ID): | oai:etheses.whiterose.ac.uk:35342 |
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