Effects of zoledronic acid versus clodronic acid on skeletal morbidity in patients with newly diagnosed multiple myeloma (MRC Myeloma IX): secondary outcomes from a randomised controlled trial
Gareth J. Morgan,J. Anthony Child,Walter M Gregory,Alex J Szubert,Kim Cocks,Sue E. Bell,Nuria Navarro-Coy,Mark T. Drayson,Roger G. Owen,Sylvia Feyler,A John Ashcroft,Fiona M. Ross,Jennifer Byrne,Huw Roddie,Claudius Rudin,Gordon Cook,Graham Jackson,Ping Wu,Faith E. Davies +18 more
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The results of this study support the early use of zoledronic acid rather than clodronic acid in patients with newly diagnosed multiple myeloma for the prevention of skeletal-related events, irrespective of bone disease status at baseline.Abstract:
Summary Background Bisphosphonates are the standard of care for reducing the risk of skeletal-related events in patients with bone lesions from multiple myeloma. The MRC Myeloma IX study was designed to compare the effects of zoledronic acid versus clodronic acid in newly diagnosed patients with multiple myeloma. Here, we report the secondary outcomes relating to skeletal events. Methods Patients (≥18 years) with newly diagnosed multiple myeloma were enrolled from 120 centres in the UK and received intensive or non-intensive antimyeloma treatment. A computer-generated randomisation sequence was used to allocate patients in a 1:1 ratio, through an automated telephone service to intravenous zoledronic acid (4 mg every 21–28 days) or oral clodronic acid (1600 mg/day), and the drugs were continued at least until disease progression. No investigators, staff, or patients were masked to treatment allocation. The primary endpoints—overall survival, progression-free survival, and overall response rate—and adverse events have been reported previously. We assessed between-group differences with Cox proportional hazards models for time to first skeletal-related event and incidence of skeletal-related events. These were defined as fractures, spinal cord compression, radiation or surgery to bone, and new osteolytic lesions. Data were analysed until disease progression. Analyses were by intention to treat. This trial is registered, number ISRCTN68454111. Findings 1960 patients were randomly assigned and analysed—981 in the zoledronic acid group and 979 in the clodronic acid group. This trial is fully enrolled, and follow-up continues. At a median follow-up of 3·7 years (IQR 2·9–4·7), patients in the zoledronic acid group had a lower incidence of skeletal-related events than did those in the clodronic acid group (265 [27%] vs 346 [35%], respectively; hazard ratio 0·74, 95% CI 0·62–0·87; p=0·0004). Zoledronic acid was also associated with a lower risk of any skeletal-related event in the subsets of patients with (233 [35%] of 668 vs 292 [43%] of 682 with clodronic acid; 0·77, 0·65–0·92; p=0·0038) and without bone lesions at baseline (29 [10%] of 302 vs 48 [17%] of 276 with clodronic acid; 0·53, 0·33–0·84; p=0·0068). Fewer patients in the zoledronic acid group had vertebral fractures than did those in the clodronic acid group (50 [5%] in the zoledronic acid group vs 88 [9%] in the clodronic acid group; p=0·0008), other fractures (45 [5%] vs 66 [7%]; p=0·04), and new osteolytic lesions (46 [5%] vs 95 [10%]; p Interpretation The results of this study support the early use of zoledronic acid rather than clodronic acid in patients with newly diagnosed multiple myeloma for the prevention of skeletal-related events, irrespective of bone disease status at baseline. Funding Medical Research Council (London, UK), Novartis, Schering Health Care, Chugai, Pharmion, Celgene, and Ortho Biotech.read more
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Bone health in cancer patients: ESMO Clinical Practice Guidelines
TL;DR: Through optimum multidisciplinary management of patients with bone metastases, including the use of bone-targeted treatments such as potent bisphosphonates or denosumab, it has been possible to transform the course of advanced cancer for many patients resulting in a major reduction in skeletal complications, reduced bone pain and improved quality of life.
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International Myeloma Working Group Consensus Statement for the Management, Treatment, and Supportive Care of Patients With Myeloma Not Eligible for Standard Autologous Stem-Cell Transplantation
Antonio Palumbo,S. Vincent Rajkumar,Jesús F. San Miguel,Alessandra Larocca,Ruben Niesvizky,Gareth J. Morgan,Ola Landgren,Roman Hájek,Hermann Einsele,Kenneth C. Anderson,Meletios A. Dimopoulos,Paul G. Richardson,Michele Cavo,Andrew Spencer,A. Keith Stewart,Kazuyuki Shimizu,Sagar Lonial,Pieter Sonneveld,Brian G.M. Durie,Philippe Moreau,Robert Z. Orlowski +20 more
TL;DR: An update on recent advances in the management of patients with multiple myeloma who are not eligible for autologous stem-cell transplantation is provided to help clinicians ensure the most appropriate care for patients with Myeloma in everyday clinical practice.
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International Myeloma Working Group Recommendations for the Treatment of Multiple Myeloma–Related Bone Disease
Evangelos Terpos,Gareth J. Morgan,Meletios A. Dimopoulos,Matthew T. Drake,Suzanne Lentzsch,Noopur Raje,Orhan Sezer,Ramón García-Sanz,Kazuyuki Shimizu,Ingemar Turesson,Tony Reiman,Artur Jurczyszyn,Giampaolo Merlini,Andrew Spencer,Xavier Leleu,Michele Cavo,Nikhil C. Munshi,S. Vincent Rajkumar,Brian G.M. Durie,G. David Roodman +19 more
TL;DR: The International Myeloma Working Group (IMWG) developed practice recommendations for the management of multiple myeloma (MM)related bone disease as discussed by the authors, and the levels of evidence and grades of recommendations were assigned and approved by panel members.
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European Myeloma Network Guidelines for the Management of Multiple Myeloma-related Complications
Evangelos Terpos,Martina Kleber,Monika Engelhardt,Sonja Zweegman,Efstathios Kastritis,Niels W.C.J. van de Donk,Benedetto Bruno,O. Sezer,Annemiek Broijl,Sara Bringhen,Meral Beksac,Alessandra Larocca,Roman Hájek,Pellegrino Musto,Hans Erik Johnsen,Fortunato Morabito,Heinz Ludwig,Michele Cavo,Hermann Einsele,Pieter Sonneveld,Meletios A. Dimopoulos,Antonio Palumbo +21 more
TL;DR: The European Myeloma Network provides recommendations for the management of the most common complications of multiple myeloma and Whole body low-dose computed tomography is more sensitive than conventional radiography in depicting osteolytic disease and thus it is recommended as the novel standard for the detection of lytic lesions in myelomas.
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Effects of Bone-Targeted Agents on Cancer Progression and Mortality
TL;DR: Increasing evidence is reviewed to support a disease-modifying effect of bone-targeted treatment and the impact on clinical management that reproductive hormones are an important treatment modifier to take into account.
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Fred Saad,Donald M. Gleason,Robin Murray,Simon Tchekmedyian,Peter Venner,Louis Lacombe,Joseph L. Chin,Jeferson J. Vinholes,J. Allen Goas,Ming Zheng +9 more
TL;DR: Long-term treatment with 4 mg of zoledronic acid is safe and provides sustained clinical benefits for men with metastatic hormone-refractory metastatic prostate cancer.
Journal Article
Zoledronic acid versus pamidronate in the treatment of skeletal metastases in patients with breast cancer or osteolytic lesions of multiple myeloma: a phase III, double-blind, comparative trial.
Lee S. Rosen,David Gordon,Mary Kaminski,Anthony Howell,Andrew R. Belch,John R. Mackey,J. Apffelstaedt,Mohamed Hussein,Robert E. Coleman,Dirk J. Reitsma,John J. Seaman,Bee Lian Chen,Yvonne Ambros +12 more
TL;DR: Zoledronic acid (4 mg) via 15-minute intravenous infusion was as effective and well tolerated as 90 mg of pamidronate in the treatment of osteolytic and mixed bone metastases/lesions in patients with advanced breast cancer or multiple myeloma.
Journal ArticleDOI
Long-term efficacy and safety of zoledronic acid compared with pamidronate disodium in the treatment of skeletal complications in patients with advanced multiple myeloma or breast carcinoma: a randomized, double-blind, multicenter, comparative trial.
Lee S. Rosen,David Gordon,Mary Kaminski,Anthony Howell,Andrew R. Belch,John R. Mackey,J. Apffelstaedt,Mohamad A. Hussein,Robert E. Coleman,Dirk J. Reitsma,Bee-Lian Chen,John J. Seaman +11 more
TL;DR: In this article, the authors compared the long-term safety and efficacy of zoledronic acid with pamidronate in patients with bone lesions secondary to advanced breast carcinoma or multiple myeloma.