Multiple myeloma and cardiovascular risk (a literature review)

Authors

  • B. B. Samura Zaporizhzhia State Medical University, Ukraine,
  • M. O. Panasenko Zaporizhzhia State Medical University, Ukraine,
  • S. Ya. Dotsenko Zaporizhzhia State Medical University, Ukraine,

DOI:

https://doi.org/10.14739/2409-2932.2020.3.216234

Keywords:

multiple myeloma, cardiovascular events, chemotherapy, diagnostics, prognostic factors

Abstract

 

Multiple myeloma is a plasma cell clonal malignancy that accounts for 10 % of hematological cancers. It predominantly affects elderly people; median age at diagnosis is 70 years. Consequently, many patients with MM have cardiovascular comorbidities or risk factors. MM can cause cardiac comorbidities such as cardiomyopathy and heart failure caused by cardiac amyloidosis and/or anemia. Heart dysfunction occuring after cytostatic drugs and monoclonal antibodies intake may act as a limiting factor in multiple myeloma treatment. Side effects of chemotherapy include hypotension, hypertension, arrhythmias, conduction disturbances, pericarditis, thromboembolic events, heart failure, death.

Advances in pharmacotherapy for MM, such as the introduction of immunomodulators, proteasome inhibitors, and monoclonal antibodies, have dramatically improved life expectancy, but new agent classes are associated with adverse effects, including cardiovascular events.

The risk of cardiotoxicity may be increased by some factors that include drug exposure, age, history of heart diseases, arterial hypertension, drug combination, previous radiotherapy or chemotherapy.

However, with careful risk assessment, monitoring, and prophylactic therapy, many of these cardiovascular complications can be managed or treated successfully. It is important to detect cardiovascular toxicity before clinical signs of heart and vessel disturbance appear. The role of markers in elicitation of cardiovascular events risk group is still uncertain.

Early definition of risk factors for prognosis of cardiovascular events appearing after polychemotherapy of multiple myeloma is an important and yet unsolved problem.

 

References

Kocoglu, M., & Badros, A. (2016). The Role of Immunotherapy in Multiple Myeloma. Pharmaceuticals, 9(1), 3. https://doi.org/10.3390/ph9010003

Palumbo, A., Bringhen, S., Ludwig, H., Dimopoulos, M. A., Bladé, J., … Sonneveld, P. (2011). Personalized therapy in multiple myeloma according to patient age and vulnerability: a report of the European Myeloma Network (EMN). Blood, 118(17), 4519-4529. https://doi.org/10.1182/blood-2011-06-358812

Kistler, K., Rajangam, K., Faich, G., & Lanes, S. (2012). Cardiac Event Rates in Patients with Newly Diagnosed and Relapsed Multiple Myeloma in US Clinical Practice. Blood, 120, 2916.

Bahlis, N. J., & Lazarus, H. M. (2006). Multiple myeloma-associated AL amyloidosis: is a distinctive therapeutic approach warranted?. Bone marrow transplantation, 38(1), 7-15. https://doi.org/10.1038/sj.bmt.1705395

Arous, S., Bensahi, I., Noureddine, M., & Habbal, R. (2015). A Typical case of a multiple myeloma revealed by cardiac amyloidosis. Angiology, 3(4), 1000163. https://doi.org/10.4172/2329-9495.1000163

International Myeloma Working Group. (2017, May 31). International Myeloma Working Group (IMWG) Criteria for the Diagnosis of Multiple Myeloma. International Myeloma Foundation. https://www.myeloma.org/international-myeloma-working-group-imwg-criteria-diagnosis-multiple-myeloma

Mayo Clinic. (2020, March 31). Mayo Foundation for Medical Education and Research. Hypercalcemia. http://www.mayoclinic.org/diseases-conditions/hypercalcemia/basics/complications/con-20031513

Gansevoort, R. T., Correa-Rotter, R., Hemmelgarn, B. R., Jafar, T. H., Heerspink, H. J., Mann, J. F., Matsushita, K., & Wen, C. P. (2013). Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention. Lancet, 382(9889), 339-352. https://doi.org/10.1016/S0140-6736(13)60595-4

Sarnak, M. J., Tighiouart, H., Manjunath, G., MacLeod, B., Griffith, J., Salem, D., & Levey, A. S. (2002). Anemia as a risk factor for cardiovascular disease in The Atherosclerosis Risk in Communities (ARIC) study. Journal of the American College of Cardiology, 40(1), 27-33. https://doi.org/10.1016/s0735-1097(02)01938-1

National Heart Lung and Blood Institute. (n.d.). Anemia. Also known as Iron-poor blood, Low blood, Tired blood. https://www.nhlbi.nih.gov/health/health-topics/topics/anemia/signs

Robinson, D., Jr, Esseltine, D. L., Regnault, A., Meunier, J., Liu, K., & van de Velde, H. (2016). The influence of baseline characteristics and disease stage on health-related quality of life in multiple myeloma: findings from six randomized controlled trials. British journal of haematology, 174(3), 368-381. https://doi.org/10.1111/bjh.14058

Moreau, P., San Miguel, J., Sonneveld, P., Mateos, M. V., Zamagni, E., Avet-Loiseau, H., Hajek, R., Dimopoulos, M. A., Ludwig, H., Einsele, H., Zweegman, S., Facon, T., Cavo, M., Terpos, E., Goldschmidt, H., Attal, M., Buske, C., & ESMO Guidelines Committee (2017). Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of oncology, 28(suppl_4), iv52-iv61. https://doi.org/10.1093/annonc/mdx096

Ludwig, H., Miguel, J. S., Dimopoulos, M. A., Palumbo, A., Garcia Sanz, R., Powles, R., Lentzsch, S., Ming Chen, W., Hou, J., Jurczyszyn, A., Romeril, K., Hajek, R., Terpos, E., Shimizu, K., Joshua, D., Hungria, V., Rodriguez Morales, A., Ben-Yehuda, D., Sondergeld, P., Zamagni, E., … Durie, B. (2014). International Myeloma Working Group recommendations for global myeloma care. Leukemia, 28(5), 981-992. https://doi.org/10.1038/leu.2013.293

Talamo, G., Dimaio, C., Abbi, K. K., Pandey, M. K., Malysz, J., Creer, M. H., Zhu, J., Mir, M. A., & Varlotto, J. M. (2015). Current role of radiation therapy for multiple myeloma. Frontiers in oncology, 5, 40. https://doi.org/10.3389/fonc.2015.00040

Shah, J. J., Orlowski, R. Z., & Thomas, S. K. (2009). Role of combination bortezomib and pegylated liposomal doxorubicin in the management of relapsed and/or refractory multiple myeloma. Therapeutics and clinical risk management, 5(1), 151-159. https://doi.org/10.2147/tcrm.s3340

European Medicines Agency. (2006, May19). Caelyx (doxorubicin hydrochloride): Janssen–Cilag International N. V. summary of product characteristics. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000089/WC500020180.pdf

Medac GmbH. (2020, May). Doxorubicin hydrochloride 2mg/ml solution for infusion. https://www.medicines.org.uk/emc/print-document?documentId=24588

Geisberg, C. A., & Sawyer, D. B. (2010). Mechanisms of anthracycline cardiotoxicity and strategies to decrease cardiac damage. Current hypertension reports, 12(6), 404-410. https://doi.org/10.1007/s11906-010-0146-y

Liu, J., Mao, W., Ding, B., & Liang, C. S. (2008). ERKs/p53 signal transduction pathway is involved in doxorubicin-induced apoptosis in H9c2 cells and cardiomyocytes. American journal of physiology. Heart and circulatory physiology, 295(5), H1956-H1965. https://doi.org/10.1152/ajpheart.00407.2008

Amgen. (2015, Novembe r19). Kyprolis (carfilzomib): summary of product characteristics. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003790/WC500197692.pdf

Takeda Pharma A/S. (2019, September 16). Ninlaro (ixazomib): summary of product characteristics. https://www.ema.europa.eu/en/documents/product-information/ninlaro-epar-product-information_en.pdf

Millennium Pharmaceuticals Ins. (2014, November). VELCADE (bortezomib): highlights of prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021602s040lbl.pdf

Kubiczkova, L., Pour, L., Sedlarikova, L., Hajek, R., & Sevcikova, S. (2014). Proteasome inhibitors - molecular basis and current perspectives in multiple myeloma. Journal of cellular and molecular medicine, 18(6), 947-961. https://doi.org/10.1111/jcmm.12279

Tannous, P., Zhu, H., Nemchenko, A., Berry, J. M., Johnstone, J. L., Shelton, J. M., Miller, F. J., Jr, Rothermel, B. A., & Hill, J. A. (2008). Intracellular protein aggregation is a proximal trigger of cardiomyocyte autophagy. Circulation, 117(24), 3070-3078. https://doi.org/10.1161/CIRCULATIONAHA.107.763870

Zhang, C., Jiang, H., Wang, P., Liu, H., & Sun, X. (2017). Transcription factor NF-kappa B represses ANT1 transcription and leads to mitochondrial dysfunctions. Scientific reports, 7, 44708. https://doi.org/10.1038/srep44708

Zamorano, J. L., Lancellotti, P., Rodriguez Muñoz, D., Aboyans, V., Asteggiano, R., … Agewall, S. (2017). 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines: The Task Force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC). European journal of heart failure, 19(1), 9-42. https://doi.org/10.1002/ejhf.654

Celgene Europe Ltd. (2017, February 16). Revlimid (lenalidomide): summary of product characteristics. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000717/WC500056018.pdf

Bayer Pharma A. G. (2011, July 21). Nexavar (sorafenib): summary of product characteristics. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000690/WC500027704.pdf

Roche Registration Ltd. (2015, January 14). Avastin, INN-bevacizumab. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000582/WC500029271.pdf

Mayo Сlinic. (2019, October 9). Prednisone and other corticosteroids. http://www.mayoclinic.org/steroids/art-20045692

Rajkumar, S. V., Jacobus, S., Callander, N. S., Fonseca, R., Vesole, D. H., Williams, M. E., Abonour, R., Siegel, D. S., Katz, M., Greipp, P. R., & Eastern Cooperative Oncology Group (2010). Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial. The Lancet. Oncology, 11(1), 29-37. https://doi.org/10.1016/S1470-2045(09)70284-0

Dimopoulos, M., Spencer, A., Attal, M., Prince, H. M., Harousseau, J. L., Dmoszynska, A., … Knight, R. D. (2007). Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. The New England journal of medicine, 357(21), 2123-2132. https://doi.org/10.1056/NEJMoa070594

Aspen trading. (2014, August). Melphalan 50 mg Powder and Solvent for Solution for Injection/Infusion. https://www.medicines.org.uk/emc/medicine/703

Medac GmbH. (2018, April). Bendamustine hydrochloride 2.5 mg/ml powder for concentrate for solution for infusion. https://www.medicines.org.uk/emc/medicine/31620

Sandoz Ltd. (2017, June 7). Cyclophosphamide 1000 mg Powder for Solution for Injection or Infusion. https://www.medicines.org.uk/emc/medicine/29592

Singla, A., Hogan, W. J., Ansell, S. M., Buadi, F. K., Dingli, D., Dispenzieri, A., … Kumar, S. K. (2013). Incidence of supraventricular arrhythmias during autologous peripheral blood stem cell transplantation. Biology of blood and marrow transplantation, 19(8), 1233-1237. https://doi.org/10.1016/j.bbmt.2013.05.019

Tzogani, K., Camarero Jiménez, J., Garcia, I., Sancho-López, A., Martin, M., Moreau, A., … Pignatti, F. (2017). The European Medicines Agency Review of Carfilzomib for the Treatment of Adult Patients with Multiple Myeloma Who Have Received at Least One Prior Therapy. The oncologist, 22(11), 1339-1346. https://doi.org/10.1634/theoncologist.2017-0184

Bovelli, D., Plataniotis, G., Roila, F., & ESMO Guidelines Working Group (2010). Cardiotoxicity of chemotherapeutic agents and radiotherapy-related heart disease: ESMO Clinical Practice Guidelines. Annals of oncology, 21 Suppl 5, v277-v282. https://doi.org/10.1093/annonc/mdq200

South west Clinical Network. (2017, December). Bortezomib, Melphalan and Prednisolone (VMP). http://www.swscn.org.uk/wp/wp-content/uploads/2014/12/VMP-1.pdf

Ludwig, H., Delforge, M., Facon, T., Einsele, H., Gay, F., Moreau, P., … Sonneveld, P. (2017). Prevention and management of adverse events of Novel agents in multiple myeloma: A consensus of the european myeloma network. Leukemia, 10.1038/leu.2017.353. https://doi.org/10.1038/leu.2017.353

Russell, S., Lyon, A., Lenihan, D., Moreau, P., Joshua, D., Chng, W., … Dimopoulos, M. (2015). Serial Echocardiographic Assessment of Patients (Pts) with Relapsed Multiple Myeloma (RMM) Receiving Carfilzomib and Dexamethasone (Kd) Vs Bortezomib and Dexamethasone (Vd): A Substudy of the Phase 3 Endeavor Trial (NCT01568866). Blood, 126, 4250.

Srkalovic, G., Cameron, M. G., Rybicki, L., Deitcher, S. R., Kattke-Marchant, K., & Hussein, M. A. (2004). Monoclonal gammopathy of undetermined significance and multiple myeloma are associated with an increased incidence of venothromboembolic disease. Cancer, 101(3), 558-566. https://doi.org/10.1002/cncr.20405

Hájek, R., Masszi, T., Petrucci, M. T., Palumbo, A., Rosiñol, L., Nagler, A., … Ludwig, H. (2017). A randomized phase III study of carfilzomib vs low-dose corticosteroids with optional cyclophosphamide in relapsed and refractory multiple myeloma (FOCUS). Leukemia, 31(1), 107-114. https://doi.org/10.1038/leu.2016.176

Dimopoulos, M. A., Goldschmidt, H., Niesvizky, R., Joshua, D., Chng, W. J., Oriol, A., Orlowski, R. Z., Ludwig, H., Facon, T., Hajek, R., Weisel, K., Hungria, V., Minuk, L., Feng, S., Zahlten-Kumeli, A., Kimball, A. S., & Moreau, P. (2017). Carfilzomib or bortezomib in relapsed or refractory multiple myeloma (ENDEAVOR): an interim overall survival analysis of an open-label, randomised, phase 3 trial. The Lancet. Oncology, 18(10), 1327-1337. https://doi.org/10.1016/S1470-2045(17)30578-8

Garderet, L., Iacobelli, S., Moreau, P., Dib, M., Lafon, I., Niederwieser, D., … Gahrton, G. (2012). Superiority of the triple combination of bortezomib-thalidomide-dexamethasone over the dual combination of thalidomide-dexamethasone in patients with multiple myeloma progressing or relapsing after autologous transplantation: the MMVAR/IFM 2005-04 Randomized Phase III Trial from the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Journal of clinical oncology, 30(20), 2475-2482. https://doi.org/10.1200/JCO.2011.37.4918

Moreau, P., Masszi, T., Grzasko, N., Bahlis, N. J., Hansson, M., Pour, L., … Laubach, J. P. (2016). Oral Ixazomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. The New England journal of medicine, 374(17), 1621-1634. https://doi.org/10.1056/NEJMoa1516282

Dimopoulos, M. A., Lonial, S., White, D., Moreau, P., Palumbo, A., San-Miguel, J., … Richardson, P. (2017). Elotuzumab plus lenalidomide/dexamethasone for relapsed or refractory multiple myeloma: ELOQUENT-2 follow-up and post-hoc analyses on progression-free survival and tumour growth. British journal of haematology, 178(6), 896-905. https://doi.org/10.1111/bjh.14787

Ludwig, H., Delforge, M., Facon, T., Einsele, H., Gay, F., Moreau, P., … Sonneveld, P. (2018). Prevention and management of adverse events of novel agents in multiple myeloma: a consensus of the European Myeloma Network. Leukemia, 32(7), 1542-1560. https://doi.org/10.1038/s41375-018-0040-1

Palumbo, A., Rajkumar, S. V., Dimopoulos, M. A., Richardson, P. G., San Miguel, J., Barlogie, B., . . . Westin, J. Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia, 22(2), 414-423. https://doi.org/10.1038/sj.leu.2405062

European Medicines Agency. (2016, April 1). Neofordex : EPAR - Product Information. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/004071/WC500204050.pdf

Chari, A., Stewart, A. K., Russell, S. D., Moreau, P., Herrmann, J., Banchs, J., . . . Lenihan, D. (2018). Analysis of carfilzomib cardiovascular safety profile across relapsed and/or refractory multiple myeloma clinical trials. Blood advances, 2(13), 1633-1644. https://doi.org/10.1182/bloodadvances.2017015545

Chari, A., Mezzi, K., Zhu, S., Werther, W., Felici, D., & Lyon, A. R. (2016). Incidence and risk of hypertension in patients newly treated for multiple myeloma: a retrospective cohort study. BMC cancer, 16(1), 912. https://doi.org/10.1186/s12885-016-2955-0

Chen-Scarabelli, C., Corsetti, G., Pasini, E., Dioguardi, F. S., Sahni, G., Narula, J., Gavazzoni, M., . . . Scarabelli, T. M. (2017). Spasmogenic Effects of the Proteasome Inhibitor Carfilzomib on Coronary Resistance, Vascular Tone and Reactivity. EBioMedicine, 21, 206-212. https://doi.org/10.1016/j.ebiom.2017.05.024

Palumbo, A., Chanan-Khan, A., Weisel, K., Nooka, A. K., Masszi, T., Beksac, M., . . . Sonneveld, P. (2016). Daratumumab, Bortezomib, and Dexamethasone for Multiple Myeloma. The New England journal of medicine, 375(8), 754-766. https://doi.org/10.1056/NEJMoa1606038

How to Cite

1.
Samura BB, Panasenko MO, Dotsenko SY. Multiple myeloma and cardiovascular risk (a literature review). Current issues in pharmacy and medicine: science and practice [Internet]. 2020Nov.16 [cited 2024Nov.23];13(3). Available from: http://pharmed.zsmu.edu.ua/article/view/216234

Issue

Section

Review