Background. We aimed to develop and validate a conceptual model of multiple myeloma (MM) that characterizes the attributes affecting disease progression and patient outcomes, and the relationships between them. Methods. Systematic and targeted literature reviews identified disease- and patient-specific attributes of MM that affect disease progression and outcomes. These attributes were validated by a Delphi panel of four international MM experts, and a physician-validated model was constructed. Real-world clinical data from the Czech Registry of Monoclonal Gammopathies (RMG) was used to confirm the relationships between attributes using pairwise correlations and multiple Cox regression analysis. Results. The Delphi panel reached consensus that most cytogenetic abnormalities influenced disease activity, which results in symptoms and complications and affects overall survival (OS). Comorbidities and complications also affect OS. The entire panel agreed that quality of life was influenced by comorbidities, age, complications, and symptoms. Consensus was not reached in some cases, in particular, the influence of del(17p) on complications. The relationships between attributes were confirmed using pairwise analysis of real-world data from the Czech RMG; most of the correlations identified were statistically significant and the strength of the correlations changed with successive relapses. Czech RMG data were also used to confirm significant predictors of OS included in the model, such as age, Eastern Cooperative Oncology Group performance status, and extramedullary disease. Conclusions. This validated conceptual model can be used for economic modeling and clinical decision making. It could also inform the development of disease-based models to explore the impact of disease progression and treatment on outcomes in patients with MM.

Amgen GmbH Rotkreuz Switzerland

Department of Hematooncology University Hospital Ostrava Ostrava Czech Republic

National and Kapodistrian University of Athens School of Medicine Athens Greece

Pharmerit International Rotterdam Netherlands

Pharmerit Ltd York UK

University Hospital of Tübingen Tübingen Germany

Würzburg University Medical Center Würzburg Germany

Zobrazit více v PubMed

de Mel S, Lim SH, Tung ML, Chng WJ. Implications of heterogeneity in multiple myeloma. Biomed Res Int. 2014;2014:232546. PubMed PMC

Dimopoulos MA, Terpos E. Multiple myeloma. Ann Oncol. 2010;21(Suppl. 7):vii143–vii150. PubMed

De Raeve HR, Vanderkerken K. The role of the bone marrow microenvironment in multiple myeloma. Histol Histopathol. 2005;20(4):1227–50. PubMed

Pulte D, Jansen L, Castro FA, et al. Trends in survival of multiple myeloma patients in Germany and the United States in the first decade of the 21st century. Br J Haematol. 2015;171(2):189–96. PubMed

Cancer Research UK. Myeloma survival statistics 2010– 2011. [cited November 26, 2015]. Available from: http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/myeloma/survival#heading-Zero

Raab MS, Cavo M, Delforge M, et al. Multiple myeloma: practice patterns across Europe. Br J Haematol. 2016;175(1):66–76. PubMed

Gay F, Palumbo A. Management of disease- and treatment-related complications in patients with multiple myeloma. Med Oncol. 2010;27(Suppl. 1):S43–S52. PubMed

Kumar SK, Therneau TM, Gertz MA, et al. Clinical course of patients with relapsed multiple myeloma. Mayo Clin Proc. 2004;79(7):867–74. PubMed

Kumar SK, Lee JH, Lahuerta JJ, et al. Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib: a multicenter International Myeloma Working Group study. Leukemia. 2012;26(1):149–57. PubMed PMC

Jakubowiak A. Management strategies for relapsed/refractory multiple myeloma: current clinical perspectives. Semin Hematol. 2012;49(Suppl. 1):S16–S32. PubMed

Janssen-Cilag International NV. VELCADE summary of product characteristics [cited December 2, 2015]. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000539/WC500048471.pdf

Amgen Europe BV. Kyprolis summary of product characteristics [cited August 2, 2016]. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003790/WC500197692.pdf

Takeda Pharma A/S. Ninlaro summary of product characteristics [cited December 16, 2016]. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003844/WC500217620.pdf

Celgene Europe Limited. Thalidomide Celgene summary of product characteristics [cited December 2, 2015]. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000823/WC500037050.pdf

Celgene Europe Limited. Revlimid summary of product characteristics [cited December 2, 2015]. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000717/WC500056018.pdf

Celgene Europe Limited. Imnovid summary of product characteristics [cited December 2, 2015]. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002682/WC500147717.pdf

Janssen-Cilag International NV. DARZALEX summary of product characteristics [cited August 8, 2016]. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/004077/WC500207296.pdf

Bristol-Myers Squibb Pharma EEIG. Empliciti summary of product characteristics [cited August 8, 2016]. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003967/WC500206673.pdf

Novartis Europharm Limited. Farydak summary of product characteristics [cited August 8, 2016]. Available from: http://ec.europa.eu/health/documents/community-register/2015/20150828132600/anx_132600_en.pdf

Roberts M, Russell LB, Paltiel AD, Chambers M, McEwan P, Krahn M ; ISPOR-SMDM Modeling Good Research Practices Task Force. Conceptualizing a model: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force–2. Value Health. 2012;15(6):804–11. PubMed PMC

Baz R, Lin HM, Hui AM, et al. Development of a conceptual model to illustrate the impact of multiple myeloma and its treatment on health-related quality of life. Support Care Cancer. 2015;23(9):2789–97. PubMed

Caro JJ, Briggs AH, Siebert U, Kuntz KM; ISPOR-SMDM Modeling Good Research Practices Task Force. Modeling good research practices—overview: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force–1. Value Health. 2012;15(6):796–803. PubMed

Tabberer M, Gonzalez-McQuire S, Muellerova H, et al. Development of a conceptual model of disease progression for use in economic modeling of chronic obstructive pulmonary disease. Med Decis Making. 2017;37(4):440–52. doi:10.1177/0272989X16662009 PubMed DOI

Radocha J, Pour L, Spicka I, et al. Registry of Monoclonal Gammopathies (RMG) in the Czech Republic. Blood. 2015;126(23):4514.

Kaltenthaler E, Tappenden P, Paisley S, Squires H. NICE DSU Technical Support Document 13: Identifying and Reviewing Evidence to Inform the Conceptualisation and Population of Cost-Effectiveness Models. London: National Institute for Health and Care Excellence; (NICE); 2011. PubMed

Hsu CC, Sandford BA. The Delphi technique: making sense of consensus. Pract Assess Res Eval. 2007;12(10):1–8.

Hájek R, Jarkovsky J, Maisnar V, et al. Survival and treatment patterns in patients with symptomatic multiple myeloma (MM) in a real-world setting. Poster presented at: European Hematology Association 21st Annual Meeting; June 9–12, 2016; Copenhagen.

Hájek R, Jarkovsky J, Bouwmeester W, et al. Predictors of overall survival (OS) in patients with multiple myeloma (MM) initiating first- and second-line treatment in the Czech Republic. Abstract presented at: 58th Annual Meeting and Exposition of the American Society of Hematology; December 3–6, 2016; San Diego.

Yancik R, Ganz PA, Varricchio CG, Conley B. Perspectives on comorbidity and cancer in older patients: approaches to expand the knowledge base. J Clin Oncol. 2001;19(4):1147–51. PubMed

Bila J, Jelicic J, Djurasinovic V, et al. Prognostic effect of comorbidity indices in elderly patients with multiple myeloma. Clin Lymphoma Myeloma Leuk. 2015;15(7):416–9. PubMed

Yong K, Delforge M, Driessen C, et al. Multiple myeloma: patient outcomes in real-world practice. Br J Haematol. 2016;175(2):252–64. PubMed PMC

Matsue K, Matsue Y, Fujisawa M, et al. Clinical features and treatment outcome of very elderly patients over 80 years old with multiple myeloma: comparison with patients in different age groups in the era of novel agents. Leuk Lymphoma. 2016;57(1):110–5. PubMed

Palumbo A, Bringhen S, Mateos MV, et al. Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an International Myeloma Working Group report. Blood. 2015;125(13):2068–74. PubMed PMC

Bird JM Owen RG, D’Sa S, et al. Guidelines for the diagnosis and management of multiple myeloma 2014. [cited March 2015]. Available from: https://academy.myeloma.org.uk/wp-content/uploads/sites/2/2014/08/MYELOMA_GUIDELINE_Feb_2014_for_BCSH1.pdf

Moreau P, Miguel JS, Ludwig H, et al. Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24(Suppl. 6):vi133–vi137. PubMed

Attal M, Harousseau JL, Stoppa AM, et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Francais du Myelome. N Engl J Med. 1996;335(2):91–7. PubMed

Child JA, Morgan GJ, Davies FE, et al. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med. 2003;348(19):1875–83. PubMed

Badros A, Goloubeva O, Dalal JS, et al. Neurotoxicity of bortezomib therapy in multiple myeloma: a single-center experience and review of the literature. Cancer. 2007;110(5):1042–9. PubMed

Corso A, Mangiacavalli S, Varettoni M, Pascutto C, Zappasodi P, Lazzarino M. Bortezomib-induced peripheral neuropathy in multiple myeloma: a comparison between previously treated and untreated patients. Leuk Res. 2010;34(4):471–4. PubMed

Dimopoulos MA, Mateos MV, Richardson PG, et al. Risk factors for, and reversibility of, peripheral neuropathy associated with bortezomib-melphalan-prednisone in newly diagnosed patients with multiple myeloma: subanalysis of the phase 3 VISTA study. Eur J Haematol. 2011;86(1):23–31. PubMed

Sonneveld P, Avet-Loiseau H, Lonial S, et al. Treatment of multiple myeloma with high-risk cytogenetics: a consensus of the International Myeloma Working Group. Blood. 2016;127(24):2955–62. PubMed PMC

Engelhardt M, Terpos E, Kleber M, et al. European Myeloma Network recommendations on the evaluation and treatment of newly diagnosed patients with multiple myeloma. Haematologica. 2014;99(2):232–42. PubMed PMC

National Institute for Health and Care Excellence. The guidelines manual 2012. [cited July 9, 2015]. Available from: https://www.nice.org.uk/process/pmg6/chapter/introduction PubMed

Aurer I, Lauc G, Dumić J, et al. Aberrant glycosylation of IgG heavy chain in multiple myeloma. Coll Antropol. 2007;31(1):247–51. PubMed

Barkay I, Maziarz RT, Chen AI, Dibb W, Chen Y, Scott EC. Extramedullary multiple myeloma associated with reduced overall survival: a retrospective single-center study. Blood. 2013;122(21):5317.

Cifci S, Yilmaz M, Pehlivan M, Sever T, Okan V, Pehlivan S. DNA repair genes polymorphisms in multiple myeloma: no association with XRCC1 (Arg399Gln) polymorphism, but the XRCC4 (VNTR in intron 3 and G-1394T) and XPD (Lys751Gln) polymorphisms is associated with the disease in Turkish patients. Hematology. 2011;16(6):361–7. PubMed

de Veas Silva JLG, Bermudo C, Harding S, Millán RD. Value of serum free light chains ratio as new biomarker of high prognostic value in patients with newly diagnosed multiple myeloma. Blood. 2013;122(21):1862.

de Veas Silva JG, Guitarte CB, Pais T, et al. Relevance of serum free light chains ratio as risk factor of poor prognosis in multiple myeloma. Clin Chem Lab Med. 2014;52:S437.

Esteves GV, Neves ML, Martins HF, et al. Serum free light chain ratio (FLCr) is a powerful prognostic factor for survival in newly diagnosed multiple myeloma (MM) in the era of new agents namely on ISS stage II patients. Blood. 2013;122(21):3150.

Esteves G, Neves ML, Martins H, et al. Serum free light chain ratio (FLCr) is a powerful prognostic factor for survival in newly diagnosed multiple myeloma (MM) eligible for high dose melphalan (HDM). Blood. 2013;122(21):1873.

Maltezas D, Sarris K, Koulieris E, et al. Increased serum transforming growth factor-beta1 (Tgf-beta1) is related to a better outcome in MM, WM and CLL patients. Blood. 2012;120(21):4976.

Niesvizky R, Richardson PG, Rajkumar SV, et al. The relationship between quality of response and clinical benefit for patients treated on the bortezomib arm of the international, randomized, phase 3 APEX trial in relapsed multiple myeloma. Br J Haematol. 2008;143(1):46–53. PubMed

Sugihara H, Chihara D, Seike K, et al. Percentage of urinary albumin excretion and serum-free light-chain reduction are important determinants of renal response in myeloma patients with moderate to severe renal impairment. Blood Cancer J. 2014;4:e235. PubMed PMC

Tovar N, de Larrea CF, Elena M, et al. Prognostic impact of serum immunoglobulin heavy/light chain ratio in patients with multiple myeloma in complete remission after autologous stem cell transplantation. Biol Blood Marrow Transplant. 2012;18(7):1076–9. PubMed

Jekarl DW, Min CK, Kwon A, et al. Impact of genetic abnormalities on the prognoses and clinical parameters of patients with multiple myeloma. Ann Lab Med. 2013;33(4):248–54. PubMed PMC

Kienle DL, Vatter C, Liebisch P, et al. Expression of ATM, MUM1, and P27 as independent prognostic markers in patients with multiple myeloma. Hematol Oncol. 2013;31:201–70.

Kuiper R, van Vliet M, Broyl A, et al. Comparison of conventional, FISH and GEP prognostic factors in multiple myeloma: introducing a novel risk stratification. Blood. 2013;122(21):3092. PubMed

Painuly U, Rajkumar V, Ketterling RP, et al. 17p deleted multiple myeloma: clinical outcomes and predictive factors for acquisition of 17p deletion. Blood. 2013;122(21):1846.

Panani AD, Ferti AD, Papaxoinis C, Raptis SA, Roussos Ch. Cytogenetic data as a prognostic factor in multiple myeloma patients: involvement of 1p12 region an adverse prognostic factor. Anticancer Res. 2004;24(6):4141–6. PubMed

Ailawadhi S, Aldoss IT, Yang D, et al. Outcome disparities in multiple myeloma: a SEER-based comparative analysis of ethnic subgroups. Br J Haematol. 2012;158(1):91–8. PubMed

Albain KS, Unger JM, Crowley JJ, Coltman CA, Jr, Hershman DL. Racial disparities in cancer survival among randomized clinical trials patients of the Southwest Oncology Group. J Natl Cancer Inst. 2009;101(14):984–92. PubMed PMC

Alexandrakis MG, Passam FJ, Ganotakis E, et al. Bone marrow microvascular density and angiogenic growth factors in multiple myeloma. Clin Chem Lab Med. 2004;42(10):1122–6. PubMed

Beason TS, Chang SH, Sanfilippo KM, et al. Influence of body mass index on survival in veterans with multiple myeloma. Oncologist. 2013;18(10):1074–9. PubMed PMC

Chen T, Berno T, Zangari M. Low-risk identification in multiple myeloma using a new 14-gene model. Eur J Haematol. 2012;89(1):28–36. PubMed

Dimopoulos MA, Kastritis E, Roussou M, et al. Renal impairment is not an independent adverse prognostic factor in multiple myeloma patients who are treated upfront with novel agent-based regimens. Blood. 2010;116(21):3033. PubMed

Rossi D, Fangazio M, De Paoli L, et al. Beta-2 microglobulin is an independent predictor of progression in asymptomatic multiple myeloma. Cancer. 2010;116(9):2188–200. PubMed

Gleason C, Nooka AK, Langston AA, et al. Survival trends of myeloma patients in the new millennium. J Clin Oncol. 2014;32:(15 Suppl.):e17694.

Hallgrimsdottir T, Porwit A, Björkholm M, et al. Bone marrow fibrosis in patients with multiple myeloma: a new prognostic factor for survival? Blood. 2013;122(21):1946.

Jordan K, Ishak KJ, Lewis P, et al. Determinants of global QOL and physical and social functionality in multiple myeloma. Blood. 2010;116(21):934.

Kang M, Jang M, Lee O, et al. Serum level of parathyroid hormone is associated with risk factors and clinical outcomes in multiple myeloma. Blood. 2013;122(21):5365.

Kim JE, Yoo C, Lee DH, Kim SW, Lee JS, Suh C. Serum albumin level is a significant prognostic factor reflecting disease severity in symptomatic multiple myeloma. Ann Hematol. 2010;89(4):391–7. PubMed

McDonagh H, Falk W, Bingman A, et al. Low testosterone levels are associated with shorter progression free survival in multiple myeloma. Blood. 2012;120(21):4978.

Terpos E, Migkou M, Christoulas D, et al. Vascular cell adhesion molecule-1 is an independent prognostic factor for newly-diagnosed patients with multiple myeloma; reductions post VD and Rd in myeloma patients at first relapse. Blood. 2013;122(21):1916.

Paiva B, Gutierrez NC, Chen X, et al. Biological and clinical significance of CD81 expression by clonal plasma cells in high-risk smoldering and symptomatic multiple myeloma (MM) patients. Blood. 2011;118(21):3936. PubMed

Pashos CL, Shah JJ, Terebelo HR, et al. Changes in patient-reported outcomes in patients diagnosed with and treated for multiple myeloma in the Connect MM Registry. J Clin Oncol. 2013;31(15 Suppl.):8586.

Patel KK, Orlowski RZ, Weber DM, et al. Prognostic value of serum lactate dehydrogenase in symptomatic multiple myeloma. J Clin Oncol. 2012;30(15 Suppl.):8093.

Rifkin RM, Abonour R, Fonseca R, et al. Connect MM: the Multiple Myeloma (MM) Disease registry—incidence of second primary malignancies (SPM). J Clin Oncol. 2012;30(15 Suppl.):8037. PubMed

Sanfilippo KM, Beason T, Chang S, et al. Effect of body mass index (BMI) at diagnosis on survival patterns of multiple myeloma (MM) patients in the Veterans Health Administration (VHA). Blood. 2012;120(21):3182.

Sewify EM, Afifi OA, Mosad E, Zaki AH, El Gammal SA. Cyclin D1 amplification in multiple myeloma is associated with multidrug resistance expression. Clin Lymphoma Myeloma Leuk. 2014;14(3):215–22. PubMed

Umeda M, Okuda S, Izumi H, et al. Prognostic significance of the serum phosphorus level and its relationship with other prognostic factors in multiple myeloma. Ann Hematol. 2006;85(7):469–73. PubMed

Yakoub-Agha I, Mary JY, Hulin C, et al. Low-dose vs high-dose thalidomide for advanced multiple myeloma: a prospective trial from the Intergroupe Francophone du Myelome. Eur J Haematol. 2012;88(3):249–59. PubMed

Ramsenthaler C, Kane P, Siegert R, et al. What are the predictors of health-related quality of life and cost in multiple myeloma? A meta-analysis. Palliat Med. 2014;28(6):631.

Shi Q, Wang XS, Shah N, et al. Prevalence of high symptom burden and its impact on functioning and quality of life in patients with multiple myeloma 3–9 months following autologous transplant. J Clin Oncol. 2014;32(15 Suppl.):e19580.

Bruns I, Büst S, Cadeddu RP, et al. Multiple myeloma infiltration impairs quantity and function of hematopoietic stem and progenitor cells leading to anemia by upregulation of the TGF-beta pathway. Onkologie. 2010;33:151.

Coleman EA, Goodwin JA, Coon SK, et al. Fatigue, sleep, pain, mood, and performance status in patients with multiple myeloma. Cancer Nurs. 2011;34(3):219–27. PubMed PMC

Pashos CL, Durie BG, Rifkin RM, et al. Race- and health-related quality of life among patients newly diagnosed with multiple myeloma. J Clin Oncol. 2012;30(Suppl.):e18556.

Strasser-Weippl K, Ludwig H. Psychosocial QOL is an independent predictor of overall survival in newly diagnosed patients with multiple myeloma. Eur J Haematol. 2008;81(5):374–9. PubMed

Alexandrakis MG, Passam FH, Kyriakou DS, Dambaki K, Niniraki M, Stathopoulos E. Ki-67 Proliferation Index: correlation with prognostic parameters and outcome in multiple myeloma. Am J Clin Oncol. 2004;27(1):8–13. PubMed

Begovic D, Radojkovic M, Kapetanovic S, et al. Preview: prognostic markers for multiple myeloma. Biochim Clin. 2013;37:S611.

Hillengass J, Wasser K, Delorme S, et al. Lumbar bone marrow microcirculation measurements from dynamic contrast-enhanced magnetic resonance imaging is a predictor of event-free survival in progressive multiple myeloma. Clin Cancer Res. 2007;13(2 Pt. 1):475–81. PubMed

Abd El-Aziz A, Hanafy SM, El-Sayed IH, El Sorady M, El Soud SA. Osteoprotegerin gene expression in multiple myeloma patients. Abstract presented at: the International Conference on Bioscience, Biotechnology, and Biochemistry; Rome, Italy; April 28–30, 2010.

de Larrea CF, Zingone A, Manasanch EE, et al. Plasma circulating proteasomes as biomarkers along natural history of asymptomatic monoclonal gammopathies. Blood. 2013;122(21):3133.

Reece DE, Zaman F, Trieu Y, et al. Relationship of treatment effects on hemoglobin and M-protein levels in relapsed or refractory multiple myeloma: final analysis of a retrospective chart review study. Blood. 2009;114(22):4892.

Pappa CA, Tsirakis G, Kanellou P, et al. Monitoring serum levels ELR+ CXC chemokines and the relationship between microvessel density and angiogenic growth factors in multiple myeloma. Cytokine. 2011;56(3):616–20. PubMed

Li C, Chen L, Gao X, et al. Plasma cell labeling index correlates with deletion of 13q14 in multiple myeloma. Leuk Lymphoma. 2011;52(2):260–4. PubMed

Landry C, Londono D, Devlin SM, et al. Multiple copies of MLL is the most commonly detected cytogenetic abnormality in newly diagnosed multiple myeloma and may modify disease risk. Blood. 2013;122(21):1910.

Alexandrakis G, Tsirakis G. Circulating levels of soluble angiogenic factors in multiple myeloma: correlation with parameters of disease activity and prognosis. Curr Angiogenesis. 2013;2(2):76–95.

Andersen NF, Vogel U, Klausen TW, et al. Vascular endothelial growth factor (VEGF) gene polymorphisms may influence the efficacy of thalidomide in multiple myeloma. Int J Cancer. 2012;131(5):E636–E642. PubMed

Andrade VC, Vettore AL, Felix RS, et al. Prognostic impact of cancer/testis antigen expression in advanced stage multiple myeloma patients. Cancer Immun. 2008;8:2–10. PubMed PMC

Barragan CS, Hansson SB, Cicchini SA, et al. Multiple myeloma, detection of four unfavorable genetic prognostic factor by interphase two-color fluorescence in situ hybridization analyses: a study of 33 patients at diagnosis or relapse. Blood. 2012;120(21):5004.

Braga W, Silva B, Bortoluzo A, et al. Impact of the expression of genes related to T regulatory cells on the survival of patients with multiple myeloma. Blood. 2012;120:4005.

Calderón C, Montero I, Vallejo A, Martín J, Martino ML. Clinical-biological profile of a group of patients with plasmacytomas: a review of homing behaviour in 68 patients with multiple myeloma. Haematologica. 2010;95:568.

Calimeri T, Fulciniti M, Lin J, et al. Aberrant non-homologous end joining in multiple myeloma: a role in genomic instability and as potential prognostic marker. Blood. 2012;120(21):2932.

Calimeri T, Samur MK, Amodio N, et al. Non Homologous end joining, a marker of genomic instability is elevated in multiple myeloma: a new prognostic factor. Blood. 2013;122(21):124. PubMed

Chung TH, Fonseca R, Chng WJ. A novel measure of chromosome instability is an independent prognostic factor in multiple myeloma. Blood. 2011;118(21):1824.

Durak BA, Akay OM, Sungar G, et al. Conventional and molecular cytogenetic analyses in Turkish patients with multiple myeloma. Turk J Haematol. 2012;29(2):135–42. PubMed PMC

Fiala MA, Finney JD, Liu J, et al. The impact of race and socioeconomic status on survival in multiple myeloma. J Clin Oncol. 2014;32(15 Suppl.):e17554.

Fonti R, Larobina M, De Luca S, et al. Metabolic tumor volume assessed by 18F-FDG-PET/CT in the evaluation of plasma cell mass and prediction of outcome in patients with multiple myeloma. Poster presented at: 23rd Annual Congress of the European Association of Nuclear Medicine; (EANM); October 9–13, 2010; Vienna, Austria.

He J, Yang L, Meng X, et al. A retrospective analysis of cytogenetic and clinical characteristics in patients with multiple myeloma. Am J Med Sci. 2013;345(2):88–93. PubMed

Heintel DH, Schreder M, Bolomsky A, et al. Treatment with lenalidomide overcomes the poor predictive influence of high IRF4 in patients with multiple myeloma. Haematologica. 2010;95:144. PubMed

Hekimgil M, Cağirgan S, Pehlivan M, Doğanavşargil B, Tombuloğlu M, Soydan S. Immunohistochemical detection of CD 95 (Fas) & Fas ligand (Fas-L) in plasma cells of multiple myeloma and its correlation with survival. Leuk Lymphoma. 2006;47(2):271–80. PubMed

Kara IO, Sahin B, Gunesacar R, Unsal C. Clinical significance of hepatocyte growth factor, platelet-derived growth factor-AB, and transforming growth factor-alpha in bone marrow and peripheral blood of patients with multiple myeloma. Adv Ther. 2006;23(4):635–45. PubMed

Kelkitli E, Atay MH, Yildiz L, Turgut M. Effect of LIM domain only (LMO2) protein expression on survival in multiple myeloma patients. J Clin Oncol. 2013;31(15 Suppl.):e19500.

Kleber M, Höck K, Ihorst G, et al. Second malignant neoplasms following multiple myeloma: a cohort study on 744 patients treated 1997–2011. Blood. 2013;122(21):3100.

Landry CA, Londono D, Devlin S, et al. Multiple copies of MLL as a commonly detected cytogenetic abnormality in newly diagnosed symptomatic multiple myeloma. J Clin Oncol. 2014;32(15 Suppl.):e19585.

Lee JH, Kim K, Kim JS, et al. Clinical profile of multiple myeloma in Asia: an Asian Myeloma Network (AMN) study. J Clin Oncol. 2012;30(15 Suppl.):8097.

Maltezas D, Tzenou T, Papanikolaou X, et al. Elevated serum B-lymphocyte stimulator levels in diagnosis are related to disease aggressiveness and adverse survival in multiple myeloma. Haematologica. 2009;94:388.

Preet M, Liu J, Axiotis CA, Braverman AS, Sidhu GS. Impact of bone marrow fibrosis (BMF) at diagnosis in patients with multiple myeloma (MM). J Clin Oncol. 2013;31(15 Suppl.):e19522.

Shah PK, Avet-Loiseau H, Minvielle S, et al. A combined survival model integrating gene expression and alternative splicing events provides higher predicative power for risk stratification. Blood. 2010;116(21):1929.

Tsirakis G, Fragioudaki M, Kaparou M, et al. Clinical and prognostic significance of elevated serum baff levels in multiple myeloma. Haematologica. 2010;95:387.

Uprety D, Churilla TM. Is overall survival in multiple myeloma associated with a shortage in health care providers? A SEER database analysis. J Clin Oncol. 2014;32(15 Suppl.):e19588.

Wu KL, Beverloo B, Lokhorst HM, et al. Abnormalities of chromosome 1p/q are highly associated with chromosome 13/13q deletions and are an adverse prognostic factor for the outcome of high-dose chemotherapy in patients with multiple myeloma. Br J Haematol. 2007;136(4):615–23. PubMed

Himani B, Meera S, Usha R. Ki67 immunostaining and its correlation with microvessel density in patients with multiple myeloma. Indian J Hematol Blood Transfus. 2013;29:324–5. PubMed

Jakob C, Sterz J, Zavrski I, et al. Angiogenesis in multiple myeloma. Eur J Cancer. 2006;42(11):1581–90. PubMed

Joshi S, Khan R, Sharma M, Kumar L, Sharma A. Angiopoietin-2: a potential novel diagnostic marker in multiple myeloma. Clin Biochem. 2011;44(8–9):590–5. PubMed

Terpos E, Christoulas D, Gkotzamanidou M, et al. Circulating periostin is elevated in patients with multiple myeloma and correlates with advanced disease features and high bone resorption. Blood. 2011;118(21):3922. PubMed

Sampaio MS, Vettore AL, Yamamoto M, Chauffaille Mde L, Zago MA, Colleoni GW. Expression of eight genes of nuclear factor-kappa B pathway in multiple myeloma using bone marrow aspirates obtained at diagnosis. Histol Histopathol. 2009;24(8):991–7. PubMed

Chae H, Ryu H, Cha K, Kim M, Kim Y, Min CK. Neutrophil gelatinase-associated lipocalin as a biomarker of renal impairment in patients with multiple myeloma. Clin Lymphoma Myeloma Leuk. 2015;15(1):35–40. PubMed

Cleeland CS, Wang XS, Thomas SK, et al. Predictive value of baseline serum MIP-1α and CRP on symptom burden and tumor response to induction therapy in patients with multiple myeloma. J Clin Oncol. 2012;30(Suppl.):8091.

Sailors MH, Wang XS, Liu P, et al. Longitudinal relationship between inflammatory markers and patient-reported symptom severity during induction therapy for multiple myeloma. J Clin Oncol. 2012;30(15 Suppl.):9083.

Vichaya EG, Wang XS, Boyette-Davis JA, et al. Baseline subclinical sensory deficits and the development of pain and numbness in patients with multiple myeloma (MM) being treated with chemotherapy. J Clin Oncol. 2012;30(15 Suppl.):9082.

Terpos E, Christoulas D, Bagratuni T, et al. High levels of periostin in patients with multiple myeloma correlate with low bone formation, increased fracture rate and diffuse MRI pattern: implications into the biology of myeloma bone disease. Blood. 2012;120(21):3967. PubMed PMC

Terpos E, Tasidou A, Roussou M, et al. Increased expression of macrophage inflammatory protein-1 alpha on trephine biopsies correlates with advanced myeloma extensive bone disease and elevated microvessel density in newly diagnosed patients with multiple myeloma. Haematologica. 2009;94:146. PubMed

Management of patients with multiple myeloma beyond the clinical-trial setting: understanding the balance between efficacy, safety and tolerability, and quality of life

Novel risk stratification algorithm for estimating the risk of death in patients with relapsed multiple myeloma: external validation in a retrospective chart review

Methodology of a Novel Risk Stratification Algorithm for Patients with Multiple Myeloma in the Relapsed Setting

Development and validation of a novel risk stratification algorithm for relapsed multiple myeloma