التفاصيل البيبلوغرافية
| العنوان: |
Carfilzomib, lenalidomide, dexamethasone, and cyclophosphamide (KRdc) as induction therapy for transplant-eligible, newly diagnosed multiple myeloma patients (Myeloma XI+): Interim analysis of an open-label randomised controlled trial |
| المؤلفون: |
Jackson, Graham H., Pawlyn, Charlotte, Cairns, David A., de Tute, Ruth M., Hockaday, Anna, Collett, Corinne, Jones, John R., Kishore, Bhuvan, Garg, Mamta, Williams, Cathy D., Karunanithi, Kamaraj, Lindsay, Jindriska, Rocci, Alberto, Snowden, John A., Jenner, Matthew W., Cook, Gordon, Russell, Nigel H., Drayson, Mark T., Gregory, Walter M., Kaiser, Martin F., Owen, Roger G., Davies, Faith E., Morgan, Gareth J. |
| المساهمون: |
Mollee, Peter N., Cancer Research UK |
| المصدر: |
PLOS Medicine ; volume 18, issue 1, page e1003454 ; ISSN 1549-1676 |
| بيانات النشر: |
Public Library of Science (PLoS) |
| سنة النشر: |
2021 |
| المجموعة: |
PLOS Publications (via CrossRef) |
| الوصف: |
Background Carfilzomib is a second-generation irreversible proteasome inhibitor that is efficacious in the treatment of myeloma and carries less risk of peripheral neuropathy than first-generation proteasome inhibitors, making it more amenable to combination therapy. Methods and findings The Myeloma XI+ trial recruited patients from 88 sites across the UK between 5 December 2013 and 20 April 2016. Patients with newly diagnosed multiple myeloma eligible for transplantation were randomly assigned to receive the combination carfilzomib, lenalidomide, dexamethasone, and cyclophosphamide (KRdc) or a triplet of lenalidomide, dexamethasone, and cyclophosphamide (Rdc) or thalidomide, dexamethasone, and cyclophosphamide (Tdc). All patients were planned to receive an autologous stem cell transplantation (ASCT) prior to a randomisation between lenalidomide maintenance and observation. Eligible patients were aged over 18 years and had symptomatic myeloma. The co-primary endpoints for the study were progression-free survival (PFS) and overall survival (OS) for KRdc versus the Tdc/Rdc control group by intention to treat. PFS, response, and safety outcomes are reported following a planned interim analysis. The trial is registered (ISRCTN49407852) and has completed recruitment. In total, 1,056 patients (median age 61 years, range 33 to 75, 39.1% female) underwent induction randomisation to KRdc ( n = 526) or control (Tdc/Rdc, n = 530). After a median follow-up of 34.5 months, KRdc was associated with a significantly longer PFS than the triplet control group (hazard ratio 0.63, 95% CI 0.51–0.76). The median PFS for patients receiving KRdc is not yet estimable, versus 36.2 months for the triplet control group ( p < 0.001). Improved PFS was consistent across subgroups of patients including those with genetically high-risk disease. At the end of induction, the percentage of patients achieving at least a very good partial response was 82.3% in the KRdc group versus 58.9% in the control group (odds ratio 4.35, 95% CI 3.19–5.94, p ... |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1371/journal.pmed.1003454 |
| الإتاحة: |
https://doi.org/10.1371/journal.pmed.1003454Test |
| حقوق: |
http://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: |
edsbas.3C3E7D8B |
| قاعدة البيانات: |
BASE |
