Literature Reviews

doi: 10.25005/2074-0581-2021-23-3-395-409
SOME ASPECTS OF EPIDEMIOLOGY, PATHOGENESIS, DIAGNOSIS AND TREATMENT OF MULTIPLE MYELOMA

S.N. Abdullaeva

Department of Internal Medicine № 3, Avicenna Tajik State Medical University, Dushanbe, Republic of Tajikistan

A literature review article provides a comprehensive overview of literature related to epidemiology, pathogenesis, diagnosis and treatment of multiple myeloma (MM). Literature data show that MM has unclear patterns of the disease distribution, and there are trends in rising incidence. Although the aetiology of MM is not fully understood, according to most researchers, risk factors (RFs) leading to a progressively high incidence of MM include advanced age, male gender, exposure to harmful environmental factors (ionising radiation, chemical agents), family predisposition, an increased prevalence of autoimmune diseases and obesity. MM is characterised by the absence of specific clinical manifestations and similarity with other conditions, which is one of the factors associated with delay in diagnosis of MM. Damage to internal organs, particularly the heart and kidneys, a frequent complication of MM, leads to mutual burdening and is also one of the factors of adverse outcomes early during the disease. The International Myeloma Working Group (IMWG) diagnostic criteria and additional investigation techniques allow high accuracy to diagnose MM and its complications. Despite the development and introduction of new drugs and treatments, the long-term survival rates in MM patient remains low. Therefore there is a need for further research in this direction.

Keywords: Multiple myeloma, cardiorenal complications, diagnostics, free light chains of immunoglobulins, treatment.

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References
  1. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391-405. Available from: https://doi.org/10.1182/blood-2016-03-643544
  2. Cid Ruzafa J, Merinopoulou E, Baggaley RF, Leighton P, Werther W, Felici D, et al. Patient population with multiple myeloma and transitions across different lines of therapy in the USA: An epidemiologic model. Pharmacoepidemiol Drug Saf. 2016;25(8):871-9. Available from: https://doi.org/10.1002/pds.3927
  3. Palumbo A, Bringhen S, Ludwig H, Dimopoulos MA, Bladé J, Mateos MV, et al. Personalized therapy in multiple myeloma according to patient age and vulnerability: A report of the European Myeloma Network (EMN). Blood. 2011;118(17):4519-29. Available from: https://doi.org/10.1182/ blood-2011-06-358812
  4. Cowan AJ, Allen C, Barac A, Basaleem H, Bensenor I, Curado MP, et al. Global burden of multiple myeloma: A systematic analysis for the Global Burden of Disease Study 2016. JAMA Oncol. 2018;4(9):1221-7. Available from: https:// doi.org/10.1001/jamaoncol.2018.2128
  5. Ozaki S. Treatment algorithms for multiple myeloma in Japan. Rinsho Ketsueki. 2017;58(8):1014-23. Available from: https://doi.org/10.11406/rinketsu. 58.1014
  6. Hong J, Lee JH. Recent advances in multiple myeloma: A Korean perspective. Korean J Intern Med. 2016;31(5):820-34. Available from: https://doi. org/10.3904/kjim.2015.408
  7. Chen XC, Chen XZ. Epidemiological differences in haematological malignancies between Europe and China. Lancet Oncol. 2014;15(11):e471-2. Available from: https://doi.org/10.1016/S1470-2045(14)70441-3
  8. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68(1):7-30. Available from: https://doi.org/10.3322/caac.21442
  9. Kazandjian D. Multiple myeloma epidemiology and survival: A unique malignancy. Semin Oncol. 2016;43(6):676-681. Available from: https://doi. org/10.1053/j.seminoncol.2016.11.004
  10. Wang S, Xu L, Feng J, Liu Y, Liu L, Wang J, et al. Prevalence and incidence of multiple myeloma in urban area in China: A national population-based analysis. Front Oncol. 2020;9:1513. Available from: https://doi.org/10.3389/ fonc.2019.01513
  11. Park EH, Lee H, Won YJ, Ju HY, Oh CM, Ingabire C, et al. Nationwide statistical analysis of myeloid malignancies in Korea: Incidence and survival rate from 1999 to 2012. Blood Res. 2015;50(4):204-17. Available from: https://doi. org/10.5045/br.2015.50.4.204
  12. Kaprin AD, Starinskiy VV, Petrova GV. Sostoyanie onkologicheskoy pomoshchi naseleniyu Rossii v 2016 godu [The state of cancer care to the population of Russia in 2016]. Moscow, RF: MNIOI im. P.A. Gertsena – filial FGBU «NMIRC» Minzdrava Rossii; 2017. 236 p.
  13. Merabishvili VM. Srednesrochnyy variantnyy prognoz smertnosti naseleniya Rossii ot zlokachestvennykh novoobrazovaniy [Medium-term prognosis of cancer mortality among the population of Russia]. Sibirskiy onkologicheskiy zhurnal. 2019;18(4):5-12. Available from: https://doi.org/10.21294/1814- 4861-2019-18-4-5-12
  14. Vinogradova OYu, Ptushkin VV, Chernikov MV, Kochkaryova YuB, Zherebtsova VA. Epidemiologiya mnozhestvennoy mielomy v gorode Moskva [Epidemiology of multiple myeloma in city Moscow]. Terapevticheskiy arkhiv. 2019;91(7):83- 92. Available from: https://doi.org/10.26442/00403660.2019.07.000305
  15. Maluskova D, Svobodová I, Kucerova M, Brozova L, Muzik J, Jarkovský J, et al. Epidemiology of multiple myeloma in the Czech Republic. Klin Onkol. 2017;30(S2):35-42. Available from: https://doi.org/10.14735/amko20172S35
  16. Curado MP, Oliveira MM, Silva DRM, Souza DLB. Epidemiology of multiple myeloma in 17 Latin American countries: An update. Cancer Med. 2018;7(5):2101- 8. Available from: https://doi.org/10.1002/cam4.1347
  17. Chang-Chan DY, Ríos-Tamayo R, Rodríguez Barranco M, Redondo-Sánchez D, González Y, Marcos-Gragera R, et al. Trends of incidence, mortality and survival of multiple myeloma in Spain. A twenty-three-year population-based study. Clin Transl Oncol. 2021. Available from: https://doi.org/10.1007/s12094-020- 02541-1
  18. Tsang M, Le M, Ghazawi FM, Cyr J, Alakel A, Rahme E, et al. Multiple myeloma epidemiology and patient geographic distribution in Canada: A population study. Cancer. 2019;125(14):2435-44. Available from: https://doi.org/10.1002/ cncr.32128
  19. Mustafakulova NI, Mirzokarimova NS, Kamolova GN, Abdullaeva SN, Kholova ShK. Komorbidnyy status i negativno vliyayushchie faktory na techenie mielomnoy bolezni v zavisimosti ot sezona goda v Respublike Tadzhikistan [Comorbid status and factors that negative influence on the course of myeloma disease depending on the season of the year in the Republic of Tajikistan]. Vestnik Akademii meditsinskikh nauk Tadzhikistana. 2019;9(4):387-94.
  20. Plummer C, Driessen C, Szabo Z, Mateos MV. Management of cardiovascular risk in patients with multiple myeloma. Blood Cancer J. 2019;9(3):26. Available from: https://doi.org/10.1038/s41408-019-0183-y
  21. Cole DC, Frishman WH. Cardiovascular complications of proteasome inhibitors used in multiple myeloma. Cardiol Rev. 2018;26(3):122-9. Available from: https://doi.org/10.1097/CRD.0000000000000183
  22. Mathur P, Thanendrarajan S, Paydak H, Vallurupalli S, Jambhekar K, Bhatti S, et al. Cardiovascular complications of multiple myeloma in the elderly. Expert Rev Cardiovasc Ther. 2017;15(12):933-43. Available from: https://doi.org/10.1080 /14779072.2017.1409114
  23. Arous S, Bensahi I, Noureddine M, Habbal R. A typical case of a multiple myeloma revealed by cardiac amyloidosis. Angiol. 2015;3:163. Available from: https://doi.org/10.4172/2329-9495.1000163
  24. Denguir H, Ben-Hamda K, Gharbi M, Addad F, Hammami S, Mlika A, et al. Cardiac amyloidosis revealing multiple myeloma. Tunis Med. 2005;83(5):300-4.
  25. Sedaghat D, Zakir RM, Choe J, Klapholz M, Saric M. Cardiac amyloidosis in a patient with multiple myeloma: A case report and review of literature. J Clin Ultrasound. 2009;37(3):179-84. Available from: https://doi.org/10.1002/ jcu.20552
  26. Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15(12):e538-48. Available from: https://doi.org/10.1016/S1470-2045(14)70442-5
  27. Gansevoort RT, Correa-Rotter R, Hemmelgarn BR, Jafar TH, Heerspink HJ, Mann JF, et al. Chronic kidney disease and cardiovascular risk: Epidemiology, mechanisms, and prevention. Lancet. 2013;382(9889):339-52. Available from: https://doi.org/10.1016/S0140-6736(13)60595-4
  28. Gulov MK, Rafiev KhK, Abdulloev SM. Epidemiologiya, faktory riska i diagnostika khronicheskoy pochechnoy nedostatochnosti [Epidemiology, risk factors and diagnosis of chronic renal failure]. Vestnik Avitsenny [Avicenna Bulletin]. 2018;20(2-3):190-6. Available from: https://doi.org/10.25005/2074-0581- 2018-20-2-3-190-196
  29. Horváth-Puhó E, Suttorp MM, Frederiksen H, Hoekstra T, Dekkers OM, Pedersen L, et al. Erythropoiesis-stimulating agents and cardiovascular events in patients with myelodysplastic syndrome and multiple myeloma. Clin Epidemiol. 2018;10:1371-80. Available from: https://doi.org/10.2147/CLEP.S172306
  30. Salahuddin AZ, Alam MR, Hossain RM, Feroz S, Zannat H, Mondal MC, et al. Renal involvement as a presenting feature of multiple myeloma. Mymensingh Med J. 2019;28(3):527-35.
  31. Gödecke V, Schmidt JJ, Bräsen JH, Koenecke C, Haller H. Diagnosis and treatment of kidney involvement in plasma cell diseases: Renal involvement in multiple myeloma and monoclonal gammopathies. Internist (Berl). 2019;60(1):10- 22. Available from: https://doi.org/10.1007/s00108-018-0538-7
  32. Hutchison CA, Batuman V, Behrens J, Bridoux F, Sirac C, Dispenzieri A, et al. The pathogenesis and diagnosis of acute kidney injury in multiple myeloma. Nat Rev Nephrol. 2011;8(1):43-51. Available from: https://doi.org/10.1038/ nrneph.2011.168
  33. Heher EC, Rennke HG, Laubach JP, Richardson PG. Kidney disease and multiple myeloma. Clin J Am Soc Nephrol. 2013;8(11):2007-17. Available from: https:// doi.org/10.2215/CJN.12231212
  34. Salogub GN. Oslozhneniya mnozhestvennoy mielomy i metody ikh korrektsii [Complications of multiple myeloma and methods of their correction]. Vestnik gematologii. 2014;10(3):39-50.
  35. De S, Kuwahara S, Saito A. The endocytic receptor megalin and its associated proteins in proximal tubule epithelial cells. Membranes (Basel). 2014;4(3):333- 55. Available from: https://doi.org/10.3390/membranes4030333
  36. Herrera GA, Joseph L, Gu X, Hough A, Barlogie B. Renal pathologic spectrum in an autopsy series of patients with plasma cell dyscrasia. Arch Pathol Lab Med. 2004;128(8):875-9. Available from: https://doi.org/10.1043/1543-2165(2004) 128<875:RPSIAA>2.0.CO;2
  37. Durie BG, Salmon SE. A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer. 1975;36(3):842-54. Available from: https://doi.org/10.1002/1097-0142(197509)36:3<842::aid-cncr2820360303> 3.0.co;2-u
  38. Greipp PR, San Miguel J, Durie BG, Crowley JJ, Barlogie B, Bladé J, et al. International staging system for multiple myeloma. J Clin Oncol. 2005;23(15):3412-20. Available from: https://doi.org/10.1200/JCO.2005.04.242
  39. International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: A report of the International Myeloma Working Group. Br J Haematol. 2003;121:749-57.
  40. Kyle RA, Rajkumar SV. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia. 2009;23(1):3-9. Available from: https://doi.org/10.1038/leu.2008.291
  41. Morrison T, Booth RA, Hauff K, Berardi P, Visram A. Laboratory assessment of multiple myeloma. Adv Clin Chem. 2019;89:1-58. Available from: https://doi. org/10.1016/bs.acc.2018.12.001
  42. Dispenzieri A, Kyle RA, Katzmann JA, Therneau TM, Larson D, Benson J, et al. Immunoglobulin free light chain ratio is an independent risk factor for progression of smoldering (asymptomatic) multiple myeloma. Blood. 2008;111(2):785- 9. Available from: https://doi.org/10.1182/blood-2007-08-108357
  43. Kyrtsonis MC, Vassilakopoulos TP, Kafasi N, Sachanas S, Tzenou T, Papadogiannis A, et al. Prognostic value of serum free light chain ratio at diagnosis in multiple myeloma. Br J Haematol. 2007;137(3):240-3. Available from: https:// doi.org/10.1111/j.1365-2141.2007.06561.x
  44. Larsen JT, Kumar SK, Dispenzieri A, Kyle RA, Katzmann JA, Rajkumar SV. Serum free light chain ratio as a biomarker for high-risk smoldering multiple myeloma. Leukemia. 2013;27(4):941-6. Available from: https://doi.org/10.1038/ leu.2012.296
  45. Rugal VI, Bessmeltsev SS. Otsenka opukholevoy infiltratsii kostnogo mozga pri mnozhestvennoy mielome po rezul’tatam issledovaniya trepanobioptatov [Evaluation of tumor infiltration of the bone marrow in multiple myeloma based on the results of a study of trepanobioptates]. Vestnik gematologii. 2009;5(1):49-50.
  46. Hillengass J, Fechtner K, Weber MA, Bäuerle T, Ayyaz S, Heiss C, et al. Prognostic significance of focal lesions in whole-body magnetic resonance imaging in patients with asymptomatic multiple myeloma. J Clin Oncol. 2010;28(9):1606- 10. Available from: https://doi.org/10.1200/JCO.2009.25.53
  47. Kastritis E, Moulopoulos LA, Terpos E, Koutoulidis V, Dimopoulos MA. The prognostic importance of the presence of more than one focal lesion in spine MRI of patients with asymptomatic (smoldering) multiple myeloma. Leukemia. 2014;28(12):2402-3. Available from: https://doi.org/10.1038/leu.2014.230
  48. Dimopoulos MA, Sonneveld P, Leung N, Merlini G, Ludwig H, Kastritis E, et al. International Myeloma Working Group recommendations for the diagnosis and management of myeloma-related renal impairment. J Clin Oncol. 2016;34(13):1544-57. Available from: https://doi.org/10.1200/ JCO.2015.65.0044
  49. Durer C, Durer S, Lee S, Chakraborty R, Malik MN, Rafae A, et al. Treatment of relapsed multiple myeloma: Evidence-based recommendations. Blood Rev. 2020;39:100616. Available from: https://doi.org/10.1016/j.blre.2019.100616
  50. Talamo G, Dimaio C, Abbi KK, Pandey MK, Malysz J, Creer MH, et al. Current role of radiation therapy for multiple myeloma. Front Oncol. 2015;5:40. Available from: https://doi.org/10.3389/fonc.2015.00040
  51. Bringhen S, Milan A, D’Agostino M, Ferri C, Wäsch R, Gay F, et al. Prevention, monitoring and treatment of cardiovascular adverse events in myeloma patients receiving carfilzomib: A consensus paper by the European Myeloma Network and the Italian Society of Arterial Hypertension. J Intern Med. 2019;286(1):63-74. Available from: https://doi.org/10.1111/joim.12882
  52. Attal M, Richardson PG, Rajkumar SV, San-Miguel J, Beksac M, Spicka I, et al. Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): A randomised, multicentre, open-label, phase 3 study. Lancet. 2019;394(10214):2096-107. Available from: https://doi. org/10.1016/S0140-6736(19)32556-5
  53. Dimopoulos MA, Dytfeld D, Grosicki S, Moreau P, Takezako N, Hori M, et al. Elotuzumab plus pomalidomide and dexamethasone for multiple myeloma. N Engl J Med. 2018;379(19):1811-22. Available from: https://doi.org/10.1056/ NEJMoa1805762
  54. Richardson PG, Oriol A, Beksac M, Liberati AM, Galli M, Schjesvold F. Pomalidomide, bortezomib, and dexamethasone for patients with relapsed or refractory multiple myeloma previously treated with lenalidomide (OPTIMISMM): A randomised, open-label, phase 3 trial. Lancet Oncol. 2019;20(6):781-94. Available from: https://doi.org/10.1016/S1470-2045(19)30152-4
  55. Wildes TM, Rosko A, Tuchman SA. Multiple myeloma in the older adult: Better prospects, more challenges. J Clin Oncol. 2014;32(24):2531-40. Available from: https://doi.org/10.1200/JCO.2014.55.1028
  56. Blimark C, Holmberg E, Mellqvist UH, Landgren O, Björkholm M, Hultcrantz M, et al. Multiple myeloma and infections: A population-based study on 9253 multiple myeloma patients. Haematologica. 2015;100(1):107-13. Available from: https://doi.org/10.3324/haematol.2014.107714
  57. Kistler KD, Rajangam K, Faich G, Lanes S. Cardiac event rates in patients with newly diagnosed and relapsed multiple myeloma in US clinical practice. Blood. 2012;120(21):2916. Available from: https://doi.org/10.1182/blood. V120.21.2916.2916
  58. Mohammadi M, Cao Y, Glimelius I, Bottai M, Eloranta S, Smedby KE. The impact of comorbid disease history on all-cause and cancer-specific mortality in myeloid leukemia and myeloma – a Swedish population-based study. BMC Cancer. 2015;15:850. Available from: https://doi.org/10.1186/s12885-015-1857-x
  59. Gregersen H, Vangsted AJ, Abildgaard N, Andersen NF, Pedersen RS, Frølund UC, et al. The impact of comorbidity on mortality in multiple myeloma: A Danish nationwide population-based study. Cancer Med. 2017;6(7):1807-16. Available from: https://doi.org/10.1002/cam4.1128
  60. Hari P, Romanus D, Luptakova K, Blazer M, Yong C, Raju A, et al. The impact of age and comorbidities on practice patterns and outcomes in patients with relapsed/refractory multiple myeloma in the era of novel therapies. J Geriatr Oncol. 2018;9(2):138-44. Available from: https://doi.org/10.1016/j. jgo.2017.09.007
  61. Lyon AR, Dent S, Stanway S, Earl H, Brezden-Masley C, Cohen-Solal A, et al. Baseline cardiovascular risk assessment in cancer patients scheduled to receive cardiotoxic cancer therapies: A position statement and new risk assessment tools from the Cardio-Oncology Study Group of the Heart Failure Association of the European Society of Cardiology in collaboration with the International Cardio-Oncology Society. Eur J Heart Fail. 2020;22(11):1945-60. Available from: https://doi.org/10.1002/ejhf.1920
  62. Bovelli D, Plataniotis G, Roila F; ESMO Guidelines Working Group. Cardiotoxicity of chemotherapeutic agents and radiotherapy-related heart disease: ESMO Clinical Practice Guidelines. Ann Oncol. 2010;21 Suppl 5:v277-82. Available from: https://doi.org/10.1093/annonc/mdq200

Author information:


Abdullaeva Sitora Navruzovna
PhD Student, Department of Internal Medicine № 3, Avicenna Tajik State Medical University
ORCID ID: 0000-0001-6834-3972
E-mail: saidxoja@gmail.com

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Abdullaeva Sitora Navruzovna
PhD Student, Department of Internal Diseases № 3, Avicenna Tajik State Medical University

734003, Republic of Tajikistan, Dushanbe, Rudaki Ave., 139

Tel.: +992 (44) 6003659

E-mail: saidxoja@gmail.com