Journal article
Long-term Follow-up of MRC Myeloma IX Trial: Survival Outcomes with Bisphosphonate and Thalidomide Treatment
Clinical cancer research, v 19(21), pp 6030-6038
01 Nov 2013
PMID: 23995858
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Purpose: Medical Research Council (MRC) Myeloma IX was a phase III trial evaluating bisphosphonate and thalidomide-based therapy for newly diagnosed multiple myeloma. Results were reported previously after a median follow-up of 3.7 years (current controlled trials number: ISRCTN68454111). Survival outcomes were reanalyzed after an extended follow-up (median, 5.9 years).
Experimental Design: At first randomization, patients (N = 1,970) were assigned to bisphosphonate (clodronic acid or zoledronic acid) and induction therapies [cyclophosphamide-vincristine-doxorubicin-dexamethasone (CVAD) or cyclophosphamide-thalidomide-dexamethasone (CTD) followed by high-dose therapy plus autologous stem cell transplantation for younger/fitter patients (intensive pathway), and melphalan-prednisone (MP) or attenuated CTD(CTDa) for older/less fit patients (nonintensive pathway)]. At second randomization, patients were assigned to thalidomide maintenance therapy or no maintenance. Interphase FISH (iFISH) was used to analyze cytogenics.
Results: Zoledronic acid significantly improved progression-free survival (PFS; HR, 0.89; P = 0.02) and overall survival (OS; HR, 0.86; P = 0.01) compared with clodronic acid. In the intensive pathway, CTD showed noninferior PFS and OS compared with CVAD, with a trend toward improved OS in patients with favorable cytogenics (P = 0.068). In the nonintensive pathway, CTDa significantly improved PFS (HR, 0.81; P = 0.007) compared with MP and there was an emergent survival benefit after 18 to 24 months. Thalidomide maintenance improved PFS (HR, 1.44; P < 0.0001) but not OS (HR, 0.96; P = 0.70), and was associated with shorter OS in patients with adverse cytogenics (P 0.01).
Conclusions: Long-term follow-up is essential to identify clinically meaningful treatment effects in myeloma subgroups based on cytogenetics. (C) 2013 AACR.
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Details
- Title
- Long-term Follow-up of MRC Myeloma IX Trial: Survival Outcomes with Bisphosphonate and Thalidomide Treatment
- Creators
- Gareth J. Morgan - Royal Marsden Hosp, Inst Canc Res, London SW3 6JJ, EnglandFaith E. Davies - Royal Marsden Hosp, Inst Canc Res, London SW3 6JJ, EnglandWalter M. Gregory - University of LeedsSusan E. Bell - University of LeedsAlexander J. Szubert - University of LeedsGordon Cook - St James Univ Hosp, Leeds, W Yorkshire, EnglandMark T. Drayson - University of BirminghamRoger G. Owen - St James Univ Hosp, Leeds, W Yorkshire, EnglandFiona M. Ross - University of SouthamptonGraham H. Jackson - Newcastle UniversityJ. Anthony Child - University of Leeds
- Publication Details
- Clinical cancer research, v 19(21), pp 6030-6038
- Publisher
- Amer Assoc Cancer Research
- Number of pages
- 9
- Grant note
- Pharmion G0100132 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); European Commission MRC Myeloma IX trial; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) Novartis Chugai Celgene; Bristol-Myers Squibb; Celgene Corporation Ortho Biotech G0100132 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) Schering Health Care Ltd.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Sociology
- Web of Science ID
- WOS:000326585300023
- Scopus ID
- 2-s2.0-84887115062
- Other Identifier
- 991020547447004721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Oncology