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Lookup NU author(s): Professor Graham Jackson
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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.
Author(s): Morgan GJ, Davies FE, Gregory WM, Bell SE, Szubert AJ, Cook G, Drayson MT, Owen RG, Ross FM, Jackson GH, Child JA
Publication type: Article
Publication status: Published
Journal: Clinical Cancer Research
Year: 2013
Volume: 19
Issue: 21
Pages: 6030-6038
Print publication date: 01/11/2013
Online publication date: 30/08/2013
Acceptance date: 27/08/2013
ISSN (print): 1078-0432
ISSN (electronic): 1557-3265
Publisher: American Association for Cancer Research
URL: http://dx.doi.org/10.1158/1078-0432.CCR-12-3211
DOI: 10.1158/1078-0432.CCR-12-3211
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