Affiliation: Institute of Cancer Research
- Role of thalidomide in the treatment of patients with multiple myelomaGareth J Morgan
Institute of Cancer Research, Royal Marsden Hospital, London, UK
Crit Rev Oncol Hematol 88:S14-22. 2013..Ongoing trials continue to evaluate novel thalidomide-based regimens to further optimize the use of thalidomide in the management of MM. ..
- How to use new biology to guide therapy in multiple myelomaGareth J Morgan
Institute of Cancer Research and Royal Marsden Hospital, London, United Kingdom
Hematology Am Soc Hematol Educ Program 2012:342-9. 2012..These combined approaches will hopefully transform the current one-for-all care into a more tailored, individual therapeutic strategy for MM patients...
- Effects of induction and maintenance plus long-term bisphosphonates on bone disease in patients with multiple myeloma: the Medical Research Council Myeloma IX TrialGareth J Morgan
The Institute of Cancer Research, Royal Marsden National Health Service Foundation Trust, London, United Kingdom
Blood 119:5374-83. 2012..02) and also from first on-study disease progression (median, 34 months for ZOL vs 27 months for CLO; P = .03). Thalidomide-containing regimens had better efficacy than traditional regimens, and ZOL demonstrated greater benefits than CLO...
- The genetic architecture of multiple myelomaGareth J Morgan
Haemato Oncology Research Unit, Division of Molecular Pathology, The Institute of Cancer Research and Royal Marsden Hospital, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK
Nat Rev Cancer 12:335-48. 2012....
- Myeloma: diagnosis complications and supportive careGareth Morgan
Institute of Cancer Research, Brookes Lawley Building, 15 Cotswold Road, Belmont, Sutton, Surrey SM2 5NG, UK
Hematology 17:S109-11. 2012..While these supportive care options are directed towards improving patient quality of life, they also have significant effect against the disease and can improve survival...
- Cyclophosphamide, thalidomide, and dexamethasone as induction therapy for newly diagnosed multiple myeloma patients destined for autologous stem-cell transplantation: MRC Myeloma IX randomized trial resultsGareth J Morgan
The Institute of Cancer Research, Royal Marsden Hospital, London, UK
Haematologica 97:442-50. 2012..Thalidomide is active in multiple myeloma and is associated with minimal myelosuppression, making it a good candidate for induction therapy prior to high-dose therapy with autologous stem-cell transplantation...
- The role of maintenance thalidomide therapy in multiple myeloma: MRC Myeloma IX results and meta-analysisGareth J Morgan
Institute of Cancer Research, Royal Marsden Hospital, London, United Kingdom
Blood 119:7-15. 2012..Overview analysis demonstrated that thalidomide maintenance was associated with a significant late OS benefit. This trial was registered at www.isrctn.org as #ISRCTN68454111...
- Targeting bone in myelomaG J Morgan
Haemato Oncology Unit, The Royal Marsden NHS Foundation Trust, Surrey, UK
Recent Results Cancer Res 192:127-43. 2012..Unravelling the mechanisms underlying myeloma-bone interactions will facilitate the development of novel therapeutic agents to treat BD, which as a consequence are likely to improve the clinical outcome of myeloma patients...
- Genomic variation in myeloma: design, content, and initial application of the Bank On A Cure SNP Panel to detect associations with progression-free survivalBrian Van Ness
Cancer Center, University of Minnesota, Minneapolis, MN, USA
BMC Med 6:26. 2008..To explore SNP associations with PFS we compared SNP profiles of short term (less than 1 year, n = 70) versus long term progression-free survivors (greater than 3 years, n = 73) in two phase III clinical trials...
- Genetic factors underlying the risk of thalidomide-related neuropathy in patients with multiple myelomaDavid C Johnson
Institute of Cancer Research, London, UK
J Clin Oncol 29:797-804. 2011..To indentify genetic variation that can modulate and predict the risk of developing thalidomide-related peripheral neuropathy (TrPN)...
- 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 trialGareth J Morgan
Section of Haemato oncology, Institute of Cancer Research, Royal Marsden NHS Foundation Trust, London, UK
Lancet Oncol 12:743-52. 2011..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...
- Can bisphosphonates improve outcomes in patients with newly diagnosed multiple myeloma?Gareth J Morgan
The Institute of Cancer Research, Royal Marsden NHS Foundation Trust, London, United Kingdom
Crit Rev Oncol Hematol 77:S24-30. 2011..Further analyses of these data will provide greater insight into ZOL interactions with primary treatment regimens for multiple myeloma...
- Cyclophosphamide, thalidomide, and dexamethasone (CTD) as initial therapy for patients with multiple myeloma unsuitable for autologous transplantationGareth J Morgan
Institute of Cancer Research, Royal Marsden Hospital, London, United Kingdom
Blood 118:1231-8. 2011..We highlight the importance of cytogenetic profiling at diagnosis and effective management of adverse events. This trial was registered at International Standard Randomized Controlled Trials Number as #68454111...
- First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): a randomised controlled trialGareth J Morgan
Institute of Cancer Research, Royal Marsden NHS Foundation Trust, London, UK
Lancet 376:1989-99. 2010..We aimed to establish whether bisphosphonates can affect clinical outcomes in patients with multiple myeloma...
- Future drug developments in multiple myeloma: an overview of novel lenalidomide-based combination therapiesGareth Morgan
Institute of Cancer Research and the Royal Marsden Hospital, London, United Kingdom
Blood Rev 24:S27-32. 2010..g. induction, salvage, or maintenance) in which they may provide the greatest impact on the disease course...
- Outcome of high-dose cytarabine-based induction therapy followed by hematopoietic stem cell transplantation in acute myeloid leukemia: influence of karyotypeBhawna Sirohi
The Royal Marsden Hospital, Surrey, UK
Leuk Lymphoma 49:2284-90. 2008..0001). These data suggest that the sequence of therapy employed is active in AML, but additional steps are needed to improve the outcome of patients with intermediate- and high-risk cytogenetic abnormalities...
- Use of single nucleotide polymorphism-based mapping arrays to detect copy number changes and loss of heterozygosity in multiple myelomaBrian A Walker
Section of Haemato oncology, Institute of Cancer Research, Surrey, UK
Clin Lymphoma Myeloma 7:186-91. 2006..In this review, we discuss the benefits of SNP-based arrays along with some of the drawbacks and how that data can be used in conjunction with expression data to identify genes with altered expression in regions of interest...
- Collection of peripheral blood stem cells in new patients with myeloma receiving minimal or no prior cytoreductive therapyBhawna Sirohi
Haemato Oncology Unit, Royal Marsden Hospital RMH and Institute of Cancer Research, Sutton, Surrey UK
Hematology 12:113-5. 2007..Using this strategy, of a single prior course of chemotherapy followed by immediate harvest, it is feasible to offer early high-dose therapy in clinical situations where this is important...
- Antitumor effects and anticancer applications of bisphosphonatesGareth Morgan
Department of Haemato Oncology, The Royal Marsden Hospital, Downs Road, Sutton, Surrey SM2 5PT, UK
Semin Oncol 37:S30-40. 2010..This review assesses the current body of preclinical and clinical evidence in favor of an antitumor effect of bisphosphonates in different cancer types...
- XBP1s levels are implicated in the biology and outcome of myeloma mediating different clinical outcomes to thalidomide-based treatmentsTina Bagratuni
Section of Haemato oncology, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, UK
Blood 116:250-3. 2010..This study highlights the importance of XBP1 in myeloma and its significance as an independent prognostic marker and as a predictor of thalidomide response...
- International Myeloma Working Group consensus statement for the management, treatment, and supportive care of patients with myeloma not eligible for standard autologous stem-cell transplantationAntonio Palumbo
Antonio Palumbo and Alessandra Larocca, University of Torino, Torino Michele Cavo, Seràgnoli Institute of Hematology, Bologna University School of Medicine, Bologna, Italy S Vincent Rajkumar, Mayo Clinic, Rochester, MN Jesus F San Miguel, University Hospital of Salamanca, Salamanca, Spain Ruben Niesvizky, Weill Cornell Medical College, New York, NY Gareth Morgan, Royal Marsden Hospital, London, United Kingdom Ola Landgren, National Cancer Institute, Bethesda, MD Roman Hajek, University of Ostrava School of Medicine and University Hospital Ostrava, Ostrava, Czech Republic Hermann Einsele, University of Wurzburg, Wurzburg, Germany Kenneth C Anderson and Paul G Richardson, Dana Farber Cancer Institute, Boston, MA Meletios A Dimopoulos, University of Athens School of Medicine, Athens, Greece Andrew Spencer, Alfred Hospital, Melbourne, Victoria, Australia A Keith Stewart, Mayo Clinic, Scottsdale, AZ Kazuyuki Shimizu, Aichi Gakuin Hospital, Department of Physiology
J Clin Oncol 32:587-600. 2014..To provide an update on recent advances in the management of patients with multiple myeloma who are not eligible for autologous stem-cell transplantation...
- Tyrosine kinase inhibitor insensitivity of non-cycling CD34+ human acute myeloid leukaemia cells with FMS-like tyrosine kinase 3 mutationsCaroline L Alvares
Section of Haemato oncology, The Institute of Cancer Research, Sutton, Surrey Department of Clinical Cytogenetics, The Royal Marsden Hospital, Sutton, Surrey
Br J Haematol 154:457-65. 2011..These findings suggest that non-cycling cells in AML may constitute a disease reservoir that is resistant to TK inhibition. Further studies with a larger sample size and other inhibitors are warranted...
- Aberrant global methylation patterns affect the molecular pathogenesis and prognosis of multiple myelomaBrian A Walker
The Institute of Cancer Research, London, UK
Blood 117:553-62. 2011..Overall, DNA methylation changes significantly during disease progression and between cytogenetic subgroups...
- A compendium of myeloma-associated chromosomal copy number abnormalities and their prognostic valueBrian A Walker
Section of Haemato oncology, The Institute of Cancer Research, London, UK
Blood 116:e56-65. 2010..This study was registered at http://isrctn.org as ISRCTN68454111...
- Mutations of the AML1 gene in acute myeloid leukemia of FAB types M0 and M7Stephen E Langabeer
Department of Haematology, University College London, London, United Kingdom
Genes Chromosomes Cancer 34:24-32. 2002..The incidence of acquired mutations in AML patients with acute megakaryoblastic leukemia (FAB type M7) was the same as that reported in other non-M0 patients, with only one mutation detected in 20 (5%) patients studied...
- Integration of global SNP-based mapping and expression arrays reveals key regions, mechanisms, and genes important in the pathogenesis of multiple myelomaBrian A Walker
Section of Haemato oncology, Institute for Cancer Research, 15 Cotswold Rd, Sutton, Surrey, United Kingdom
Blood 108:1733-43. 2006..We have documented these genes, providing a focus for further studies to identify and characterize those that are key in the pathogenesis of myeloma...
- MyelomA Genetics International ConsortiumGareth Morgan
The Institute of Cancer Research, London, UK
Leuk Lymphoma 53:796-800. 2012..Here, we review the rationale for identifying genetic risk variants for MM and our proposed strategy for establishing MAGIC...
- Homozygous deletion mapping in myeloma samples identifies genes and an expression signature relevant to pathogenesis and outcomeNicholas J Dickens
Section of Haemato oncology, The Institute of Cancer Research, London, United Kingdom
Clin Cancer Res 16:1856-64. 2010..However, these indicators do not capture all prognostic information. Gene expression analysis can be used to identify poor-prognosis patients and this can be improved by combination with information about DNA-level changes...
- Gene mapping and expression analysis of 16q loss of heterozygosity identifies WWOX and CYLD as being important in determining clinical outcome in multiple myelomaMatthew W Jenner
Section of Haemato oncology, Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, UK
Blood 110:3291-300. 2007..These 2 genes and their corresponding pathways provide an important insight into the potential mechanisms by which 16q LOH confers poor prognosis...
- Long-term outcomes of previously untreated myeloma patients: responses to induction chemotherapy and high-dose melphalan incorporated within a risk stratification model can help to direct the use of novel treatmentsCaroline L Alvares
Haemato Oncology Unit, Royal Marsden Hospital, Sutton, Surrey, UK
Br J Haematol 129:607-14. 2005..We propose a multiparametric risk-adapted model that includes response to induction chemotherapy and HDM, for identifying patients who may benefit from novel approaches to treatment...
- Survival and outcome of blastoid variant myeloma following treatment with the novel thalidomide containing regime DT-PACEMuralikrishnan Srikanth
Haemato Oncology Unit, The Royal Marsden Hospital, Sutton, Surrey, UK
Eur J Haematol 81:432-6. 2008..In conclusion, the clinical outcome of this group of cases is poor even when treated with the intensive regimen DT-PACE; however, a subgroup can do well if DT-PACE is consolidated by ASCT...
- Bendamustine, thalidomide and dexamethasone combination therapy for relapsed/refractory myeloma patients: results of the MUKone randomized dose selection trialSteve Schey
Department of Haematology, King s College Hospital, London, UK
Br J Haematol 170:336-48. 2015..This study demonstrates bendamustine at 60 mg/m2 twice per month with thalidomide and dexamethasone is deliverable for repeated cycles in heavily pre-treated myeloma patients and has substantial clinical activity...
- European perspective on multiple myeloma treatment strategies in 2014Heinz Ludwig
Department of Oncology, Hematology and Palliative Care, Wilhelminenspital, Vienna, Austria Department of Hematology, Erasmus Medical Center, Rotterdam, The Netherlands Institute of Cancer Research, Royal Marsden Hospital, London, United Kingdom Department of Hematology, Institut d Investigacions Biomediques August Pi i Sunyer, Hospital Clinic, Barcelona, Spain Divisione di Ematologia dell Università di Torino, Azienda Ospedaliera S Giovanni Battista, Ospedale Molinette, Turin, Italy Institute of Hematology and Medical Oncology, Seragnoli, Bologna, Italy Haemato Oncology Unit, Royal Marsden Hospital, Surrey, United Kingdom Hematology Service, University Hospital La Fe, Valencia, Spain Department of Hematology, University Hospital, Leuven, Belgium Department of Clinical Therapeutics, University of Athens School of Medicine, Athens, Greece Universitätsklinik Würzburg, Medizinische Klinik und Poliklinik II, Wurzburg, Germany Service d Hématologie, Centre Hospitalier Universitaire, Lille, France Department of Internal Medicine V, University of Heidelberg, Heidelberg, McLean Hospital/Harvard Medical School
Oncologist 19:829-44. 2014..A substantial number of new drugs and novel drug classes in early clinical development have shown promising activity. Their introduction into clinical practice will most likely further improve treatment results. ..
- Characterising the TP53-deleted subgroup of chronic lymphocytic leukemia: an analysis of additional cytogenetic abnormalities detected by interphase fluorescence in situ hybridisation and array-based comparative genomic hybridisationHannah C Rudenko
Section of Haemato oncology, The Institute of Cancer Research ICR, Sutton, Surrey, London, UK
Leuk Lymphoma 49:1879-86. 2008..02). In particular, amplification of 2p and deletion of 6q were both more frequent. Cases with >20%TP53-deleted cells had the worst prognosis in the LRF CLL4 trial...
- Neuron-specific enolase expression in multiple myelomaRicky A Sharma
Department of Radiotherapy, Royal Marsden Hospital, London, UK
Lancet Oncol 7:960. 2006
- An update on drug combinations for treatment of myelomaMuralikrishnan Srikanth
The Royal Marsden Hospital, Department of Haemato Oncology, Downs Road, Sutton, Surrey SM2 5PT, UK
Expert Opin Investig Drugs 17:1-12. 2008..This represents a challenge for both drug development and clinical trial evaluation, which has the potential to revolutionise the clinical management of myeloma and a paradigm for drug development in other diseases...
- The addition of cyclophosphamide to lenalidomide and dexamethasone in multiply relapsed/refractory myeloma patients; a phase I/II studyStephen A Schey
Department of Haematological Medicine, King s College Hospital, London, UK
Br J Haematol 150:326-33. 2010..Lenalidomide, cyclophosphamide and dexamethasone is a safe, effective combination in relapsed myeloma inducing a high response rate, warranting further investigation in phase III trials...
- Multiple autophosphorylations significantly enhance the endoribonuclease activity of human inositol requiring enzyme 1αDaniel Itzhak
From the Division of Cancer Therapeutics, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK
BMC Biochem 15:3. 2014..Kinase activity can also be made redundant by small molecules which bind the ATP binding site. We set out to uncover a role for IRE1α kinase activity using wild-type cytosolic protein constructs...
- Haplotypes in the tumour necrosis factor region and myelomaGareth J Morgan
Section of Haemato oncology, Institute for Cancer Research, Royal Marsden Hospital, London, UK
Br J Haematol 129:358-65. 2005..57; 95% confidence interval, 0.38-0.86. The results of this study did not support our starting hypothesis; that high producer haplotypes at the TNF locus are associated with an increased risk of developing myeloma...
- Advances in oral therapy for multiple myelomaGareth J Morgan
Royal Marsden Hospital and Institute of Cancer Research, London, UK
Lancet Oncol 7:316-25. 2006....
- The combination of cyclophosphomide, thalidomide and dexamethasone is an effective alternative to cyclophosphamide - vincristine - doxorubicin - methylprednisolone as induction chemotherapy prior to autologous transplantation for multiple myeloma: a case-Ping Wu
Haemato Oncology Unit, Royal Marsden Hosptial, Sutton, Surrey, UK
Leuk Lymphoma 47:2335-8. 2006..60%, P = 0.0002) with CVAMP and more thrombotic episodes with CTD (11% vs. 4%). CTD may emerge as the superior induction regimen prior to PBSCT, in terms of high efficacy and better tolerability...
- Proteasome inhibition and multiple myelomaPamela Kanagasabaphy
Royal Marsden Hospital, Haemato Oncology Unit, Downs Road, Sutton, Surrey SM2 5PT, UK
Curr Opin Investig Drugs 8:447-51. 2007..The role of proteasome inhibitors in the management of myeloma is also discussed...
- Immunoglobulin gene rearrangements and the pathogenesis of multiple myelomaDavid Gonzalez
Section of Haemato oncology, Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, UK
Blood 110:3112-21. 2007..Herein, we review the data currently available on both Ig gene rearrangements and protein patterns seen in myeloma with the aim of illustrating how this knowledge has contributed to our understanding of the pathobiology of myeloma...
- Genetic associations with thalidomide mediated venous thrombotic events in myeloma identified using targeted genotypingDavid C Johnson
Section of Haemato oncology, Institute of Cancer Research, London, United Kingdom
Blood 112:4924-34. 2008..The clinical trials described in this paper have been registered as follows: MRC Myeloma IX: ISRCTN68454111; Hovon-50: NCT00028886; and ECOG EA100: NCT00033332...
- Deletions of CDKN2C in multiple myeloma: biological and clinical implicationsPaola E Leone
Section of Haemato oncology, The Institute of Cancer Research, 15 Cotswold Road, London, United Kingdom
Clin Cancer Res 14:6033-41. 2008..3 has been identified in myeloma cell lines as the potential target of the deletion. We tested the clinical impact of 1p deletion and used high-resolution techniques to define the role of CDKN2C in primary patient material...
- MMSET deregulation affects cell cycle progression and adhesion regulons in t(4;14) myeloma plasma cellsJose L R Brito
Institute for Cancer Research, Section of Haemato oncology, London, UK
Haematologica 94:78-86. 2009..The involvement of MMSET in the pathogenesis of t(4;14) multiple myeloma and the mechanism or genes deregulated by MMSET upregulation are still unclear...
- Gender disparities in the tumor genetics and clinical outcome of multiple myelomaKevin D Boyd
The Institute of Cancer Research, Section of Haemato oncology, London, United Kingdom
Cancer Epidemiol Biomarkers Prev 20:1703-7. 2011..Several cancer types have differences in incidence and clinical outcome dependent on gender, but these are not well described in myeloma. The aim of this study was to characterize gender disparities in myeloma...
- Streptolysin-O reversible permeabilisation is an effective method to transfect siRNAs into myeloma cellsJose L R Brito
Institute for Cancer Research, Section of Haemato oncology, SM2 5NG, London, UK
J Immunol Methods 333:147-55. 2008..These studies demonstrate that reversible SLO permeabilisation can successfully be applied to hard-to-transfect human myeloma cell lines to effectively silence genes...
- Untangling the unfolded protein responseEmma L Davenport
Section of Haemato oncology, The Institute of Cancer Research, Sutton, Surrey, UK
Cell Cycle 7:865-9. 2008..In this article, based on work in multiple myeloma, we highlight the importance of targeting multiple signalling pathways simultaneously, using the UPR and heat shock proteins as examples, as a means of effectively killing cancer cells...
- Heat shock protein inhibition is associated with activation of the unfolded protein response pathway in myeloma plasma cellsEmma L Davenport
Section of Haemato oncology, Cancer Research UK, The Institute of Cancer Research, Sutton, Surrey, UK
Blood 110:2641-9. 2007..All drugs inhibited proliferation and induced cell death with activation of JNK and caspase cleavage. In conclusion, Hsp90 inhibitors induce myeloma cell death at least in part via endoplasmic reticulum stress and the UPR death pathway...
- Non-Hodgkin lymphoma secondary to cancer chemotherapyBiju Krishnan
Section of Hemato Oncology, Institute of Cancer Research, Sutton, Surrey, SM2 5NG, United Kingdom
Cancer Epidemiol Biomarkers Prev 16:377-80. 2007..This reinforces the need for long-term follow-up of all patients exposed to chemoradiotherapy and confirms that chemotherapeutic agents can cause lymphoma...
- Aminopeptidase inhibition as a targeted treatment strategy in myelomaHannah E Moore
Section of Haemato oncology, Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, United Kingdom
Mol Cancer Ther 8:762-70. 2009..In conclusion, inhibiting protein turnover using the aminopeptidase inhibitor CHR-2797 results in myeloma cell apoptosis and represents a novel therapeutic approach that warrants further investigation in the clinical setting...