دورية أكاديمية
The Impact of Autologous Stem Cell Transplantation on the Genetics of High-Risk Relapsed Multiple Myeloma
| العنوان: | The Impact of Autologous Stem Cell Transplantation on the Genetics of High-Risk Relapsed Multiple Myeloma |
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| المؤلفون: | Shahin, M, Pawlyn, C, Weinhold, N, Ashby, TC, Walker, BA, Wardell, CP, Cairns, D, Menzies, T, Gregory, WM, Kaiser, MF, Cook, G, Drayson, MT, Owen, RG, Jackson, G, Davies, FE, Morgan, GJ, Jones, JR |
| بيانات النشر: | American Society of Hematology |
| سنة النشر: | 2022 |
| المجموعة: | White Rose Research Online (Universities of Leeds, Sheffield & York) |
| الوصف: | Introduction: Autologous stem cell transplant (ASCT) followed by maintenance lenalidomide remains standard of care for newly diagnosed eligible myeloma patients. An understanding of how these treatments impact the genetic profile of the myeloma clone at relapse are lacking. We have previously shown that depth of response impacts clonal evolution at relapse. Here we explore the impact of melphalan conditioned ASCT as an additional factor in inducing genetic change. We used whole exome sequencing (WES) data from paired samples for a series of 56 newly diagnosed patients treated in the NCRI Myeloma XI Trial. Methods: The Myeloma XI trial recruited patients to both ASCT and non-ASCT pathways. Within both pathways patients were randomised to an induction regime of either thalidomide or lenalidomide with cyclophosphamide and dexamethasone. Following induction, and ASCT if eligible, patients were further randomised to observation or lenalidomide maintenance. WES was undertaken on presentation and relapse malignant plasma cells (122x, n=22 ASCT, 34 non-ASCT). The mutational load and profile, structural aberrations, and evolutionary mechanism leading to relapse was determined. The series of patients were all phenotypically high risk, defined as relapse within 30 months of treatment initiation. The median PFS from maintenance randomisation was 19 months. Best response prior to relapse was determined for all; CR/nCR = 50% ASCT, 39% non-ASCT, VGPR/PR = 50% ASCT, 61% non-ASCT. Results: In the patients who had undergone ASCT there was a significant increase in non-synonymous (NS) mutations between presentation and relapse (32 vs 49, p=0.005). This was not seen in the non-ASCT patients (43 vs 44, p=0.53). When breaking down the mutational load according to response, only ASCT patients achieving a CR/nCR had a significant increase in the NS mutational load from 28 to 58 (p=0.003). We profiled 24 mutations known to be recurrent in myeloma. To infer possible clonal evolution, we determined whether there was a change in the ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| العلاقة: | Shahin, M, Pawlyn, C, Weinhold, N et al. (14 more authors) (2022) The Impact of Autologous Stem Cell Transplantation on the Genetics of High-Risk Relapsed Multiple Myeloma. Blood, 140 (Supplement 1). pp. 4232-4233. ISSN 0006-4971 |
| DOI: | 10.1182/blood-2022-169628 |
| الإتاحة: | https://doi.org/10.1182/blood-2022-169628Test https://eprints.whiterose.ac.uk/200019Test/ |
| رقم الانضمام: | edsbas.C23169A7 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1182/blood-2022-169628 |
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