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Current Treatment Options in Cardiovascular Medicine
Published in: Current Treatment Options in Cardiovascular Medicine 3/2018

01-03-2018 | Cardio-oncology (M Fradley, Section Editor)

Cardiovascular Complications of Multiple Myeloma Treatment: Evaluation, Management, and Prevention

Authors: Dae Hyun Lee, MD, Michael G. Fradley, MD

Published in: Current Treatment Options in Cardiovascular Medicine | Issue 3/2018

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Abstract

Purpose of review

Multiple myeloma treatment regimens consist of proteasome inhibitors (bortezomib, carfilzomib, and ixazomib), immunomodulatory drugs (thalidomide, lenalidomide, and pomalidomide), and steroids. In this paper, we will review the pathophysiology and associated cardiotoxicities of the different multiple myeloma therapeutic modalities and present methods to mitigate the development of cardiovascular complications.

Recent findings

Although proteasome inhibitors and immunomodulatory drugs have led to significant improvements in oncologic outcomes, there is increasing evidence of serious cardiovascular side effects which may be exacerbated in the setting of underlying cardiovascular risk factors or disease. Cardiotoxicities include cardiomyopathy and heart failure, accelerated hypertension, arrhythmias, and both arterial and venous thromboembolism.

Summary

Given the frequency of cardiovascular risk factors in multiple myeloma patients as well as the cardiotoxicities associated with the different treatment regimens, it is essential to closely monitor these patients. Collaboration between cardiologists and oncologists is necessary to ensure patients receive optimal cancer treatment while minimizing cardiovascular risk.
Literature
1.
2.
3.
4.
Quach H, Ritchie D, Stewart AK, Neeson P, Harrison S, Smyth MJ, et al. Mechanism of action of immunomodulatory drugs (IMiDS) in multiple myeloma. Leukemia. 2010;24:22–32.PubMedCrossRef
5.
Lu G, Middleton RE, Sun H, Naniong M, Ott CJ, Mitsiades CS, et al. The myeloma drug lenalidomide promotes the cereblon-dependent destruction of Ikaros proteins. Science. 2014;343:305–9.PubMedCrossRef
6.
7.
Alexanian R, Dimopoulos MA, Delasalle K, Barlogie B. Primary dexamethasone treatment of multiple myeloma. Blood. 1992;80:887.PubMed
8.
Li W, Cornell RF, Lenihan D, Slosky D, Jagasia M, Piazza G, et al. Cardiovascular complications of novel multiple myeloma treatments. Circulation. 2016;133:908–12.PubMedCrossRef
9.
• Kistler KD, Kalman J, Sahni G, Murphy B, Werther W, Rajangam K, et al. Incidence and risk of cardiac events in patients with previously treated multiple myeloma versus matched patients without multiple myeloma: an observational, retrospective, cohort study. Clin Lymphoma Myeloma Leuk. 2017;17:89–96.e3. Large insurance database study demonstrating increased rates of cardiovascular disease in multiple myeloma patients compared to matched control patients.PubMedCrossRef
10.
Falanga A, Marchetti M. Venous thromboembolism in the hematologic malignancies. J Clin Oncol. 2009;27:4848–57.PubMedCrossRef
11.
•• Siegel D, Martin T, Nooka A, Harvey RD, Vij R, Niesvizky R, et al. Integrated safety profile of single-agent carfilzomib: experience from 526 patients enrolled in 4 phase II clinical studies. Haematologica. 2013;98:1753–61. This study provides a comprehensive assessment of carfilzomib-associated cardiotoxicity from data compiled from four phase II clinical trials.PubMedPubMedCentralCrossRef
12.
Richardson PG, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin D, et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med. 2003;348:2609–17.PubMedCrossRef
13.
Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, Facon T, et al. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med. 2005;352:2487–98.PubMedCrossRef
14.
Jagannath S, Barlogie B, Berenson J, Siegel D, Irwin D, Richardson PG, et al. A phase 2 study of two doses of bortezomib in relapsed or refractory myeloma. Br J Haematol. 2004;127:165–72.PubMedCrossRef
15.
San Miguel JF, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M, et al. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med. 2008;359:906–17.PubMedCrossRef
16.
Dasanu CA. Complete heart block secondary to bortezomib use in multiple myeloma. J Oncol Pharm Pract. 2010;17:282–4.PubMedCrossRef
17.
Lee W-S, Kim D-H, Shin S-H, Woo S-I, Kwan J, Park K-S, et al. Complete atrioventricular block secondary to bortezomib use in multiple myeloma. Yonsei Med J. 2011;52:196.PubMedCrossRef
18.
Diwadkar S, Patel AA, Fradley MG. Bortezomib-induced complete heart block and myocardial scar: the potential role of cardiac biomarkers in monitoring cardiotoxicity. Case Rep Cardiol. 2016;2016(3):456,287–5.
19.
Orciuolo E, Buda G, Cecconi N, Galimberti S, Versari D, Cervetti G, et al. Unexpected cardiotoxicity in haematological bortezomib treated patients. Br J Haematol. 2007;138:396–7.CrossRef
20.
Gupta A, Pandey A, Sethi S. Bortezomib-induced congestive cardiac failure in a patient with multiple myeloma. Cardiovasc Toxicol. 2011;12:184–7.CrossRef
21.
Bockorny M, Chakravarty S, Schulman P, Bockorny B, Bona R. Severe heart failure after bortezomib treatment in a patient with multiple myeloma: a case report and review of the literature. Acta Haematol. 2012;128:244–7.PubMedCrossRef
22.
Takamatsu H, Yamashita T, Kotani T, Sawazaki A, Okumura H, Nakao S. Ischemic heart disease associated with bortezomib treatment combined with dexamethasone in a patient with multiple myeloma. Int J Hematol. 2010;91:903–6.PubMedCrossRef
23.
Honton B, Despas F, Dumonteil N, Rouvellat C, Roussel M, Carrie D, et al. Bortezomib and heart failure: case-report and review of the French Pharmacovigilance database. Fundam Clin Pharmacol. 2013;28:349–52.PubMedCrossRef
24.
Xiao Y, Yin J, Wei J, Shang Z. Incidence and risk of cardiotoxicity associated with bortezomib in the treatment of cancer: a systematic review and meta-analysis. Moretti C, editor. PLoS ONE. 2014;9:e87671.
25.
•• Laubach JP, Moslehi JJ, Francis SA, San Miguel JF, Sonneveld P, Orlowski RZ, et al. A retrospective analysis of 3954 patients in phase 2/3 trials of bortezomib for the treatment of multiple myeloma: towards providing a benchmark for the cardiac safety profile of proteasome inhibition in multiple myeloma. Br J Haematol. 2017;178:547–60. Large retrospective analysis confirming the lack of significant cardiotoxicity with the proteasome inhibitor bortezomib.PubMedCrossRef
26.
•• Dimopoulos MA, Moreau P, Palumbo A, Joshua D, Pour L, Hájek R, et al. Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study. Lancet Oncol. 2016;17:27–38. The ENDEAVOR trial demonstrated improved efficacy and cancer outcomes with carfilzomib compared to bortezomib but also reported increased rates of cardiotoxicities with carfilzomib.PubMedCrossRef
27.
Orlowski RZ, Nagler A, Sonneveld P, Bladé J, Hájek R, Spencer A, et al. Randomized phase III study of pegylated liposomal doxorubicin plus bortezomib compared with bortezomib alone in relapsed or refractory multiple myeloma: combination therapy improves time to progression. J Clin Oncol. 2007;25:3892–901.PubMedCrossRef
28.
Moreau P, Pylypenko H, Grosicki S, Karamanesht I, Leleu X, Grishunina M, et al. Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study. Lancet Oncol. 2011;12:431–40.PubMedCrossRef
29.
Hájek R, Masszi T, Petrucci MT, Palumbo A, Rosiñol L, Nagler A, et al. A randomized phase III study of carfilzomib vs low-dose corticosteroids with optional cyclophosphamide in relapsed and refractory multiple myeloma (FOCUS). Leukemia. 2016;31:107–14.PubMedPubMedCentralCrossRef
30.
Siegel DS, Martin T, Wang M, Vij R, Jakubowiak AJ, Lonial S, et al. A phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma. Blood. 2012;120:2817–25.PubMedPubMedCentralCrossRef
31.
Vij R, Wang M, Kaufman JL, Lonial S, Jakubowiak AJ, Stewart AK, et al. An open-label, single-arm, phase 2 (PX-171-004) study of single-agent carfilzomib in bortezomib-naive patients with relapsed and/or refractory multiple myeloma. Blood. 2012;119:5661–70.PubMedPubMedCentralCrossRef
32.
Weber D, Rankin K, Gavino M, Delasalle K, Alexanian R. Thalidomide alone or with dexamethasone for previously untreated multiple myeloma. J Clin Oncol. 2003;21:16–9.PubMedCrossRef
33.
Carrier M, Le Gal G, Tay J, Wu C, Lee AY. Rates of venous thromboembolism in multiple myeloma patients undergoing immunomodulatory therapy with thalidomide or lenalidomide: a systematic review and meta-analysis. J Thromb Haemost. 2011;9:653–63.PubMedCrossRef
34.
Cavo M, Tacchetti P, Patriarca F, Petrucci MT, Pantani L, Galli M, et al. Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study. Lancet. 2010;376:2075–85.PubMedCrossRef
35.
Palumbo A, Cavo M, Bringhen S, Cavalli M, Patriarca F, Rossi D, et al. A phase III study of enoxaparin vs aspirin vs low-dose warfarin as thromboprophylaxis for newly diagnosed myeloma patients treated with thalidomide based-regimens. Blood. 2009;114:492.
36.
Rosiñol L, Oriol A, Teruel AI, Hernández D, López-Jiménez J, de la Rubia J, et al. Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: a randomized phase 3 PETHEMA/GEM study. Blood. 2012;120:1589–96.PubMedCrossRef
37.
Stewart AK, Rajkumar SV, Dimopoulos MA, Masszi T, Špička I, Oriol A, et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2015;372:142–52.PubMedCrossRef
38.
Mateos M-V, Masszi T, Grzasko N, Hansson M, Sandhu I, Pour L, et al. Impact of prior therapy on the efficacy and safety of oral ixazomib-lenalidomide-dexamethasone vs. placebo-lenalidomide-dexamethasone in patients with relapsed/refractory multiple myeloma in TOURMALINE-MM1. Haematologica. 2017;102:1767–75.PubMedPubMedCentralCrossRef
39.
Weber DM, Chen C, Niesvizky R, Wang M, Belch A, Stadtmauer EA, et al. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med. 2007;357:2133–42.PubMedCrossRef
40.
Dimopoulos M, Spencer A, Attal M, Prince HM, Harousseau J-L, Dmoszynska A, et al. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med. 2007;357:2123–32.PubMedCrossRef
41.
Knight R, DeLap RJ, Zeldis JB. Lenalidomide and venous thrombosis in multiple myeloma. N Engl J Med. 2006;354:2079–80.PubMedCrossRef
42.
Durie BGM, Hoering A, Abidi MH, Rajkumar SV, Epstein J, Kahanic SP, et al. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. Lancet. 2017;389:519–27.PubMedCrossRef
43.
Rajkumar SV, Jacobus S, Callander NS, Fonseca R, Vesole DH, Williams ME, et al. 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. Lancet Oncol. 2010;11:29–37.PubMedCrossRef
44.
Menon SP, Rajkumar SV, Lacy M, Falco P, Palumbo A. Thromboembolic events with lenalidomide-based therapy for multiple myeloma. Cancer. 2008;112:1522–8.PubMedPubMedCentralCrossRef
45.
Zonder JA, Barlogie B, Durie BGM, McCoy J, Crowley J, Hussein MA. Thrombotic complications in patients with newly diagnosed multiple myeloma treated with lenalidomide and dexamethasone: benefit of aspirin prophylaxis. Blood. 2006;108:403–4.PubMedCrossRef
46.
Richardson PG, Siegel DS, Vij R, Hofmeister CC, Baz R, Jagannath S, et al. Pomalidomide alone or in combination with low-dose dexamethasone in relapsed and refractory multiple myeloma: a randomized phase 2 study. Blood. 2014;123:1826–32.PubMedPubMedCentralCrossRef
47.
Leleu X, Attal M, Arnulf B, Moreau P, Traulle C, Marit G, et al. Pomalidomide plus low-dose dexamethasone is active and well tolerated in bortezomib and lenalidomide-refractory multiple myeloma: Intergroupe Francophone du Myelome 2009-02. Blood. 2013;121:1968–75.PubMedCrossRef
48.
Moreau P, Dimopoulos MA, Richardson PG, Siegel DS, Cavo M, Corradini P, et al. Adverse event management in patients with relapsed and refractory multiple myeloma taking pomalidomide plus low-dose dexamethasone: a pooled analysis. Eur J Haematol. 2017;99:199–206.PubMedCrossRef
49.
Lacy MQ, Allred JB, Gertz MA, Hayman SR, Short KD, Buadi F, et al. Pomalidomide plus low-dose dexamethasone in myeloma refractory to both bortezomib and lenalidomide: comparison of 2 dosing strategies in dual-refractory disease. Blood. 2011;118:2970–5.PubMedPubMedCentralCrossRef
50.
Richardson PG, Siegel D, Baz R, Kelley SL, Munshi NC, Laubach J, et al. Phase 1 study of pomalidomide MTD, safety, and efficacy in patients with refractory multiple myeloma who have received lenalidomide and bortezomib. Blood. 2013;121:1961–7.PubMedPubMedCentralCrossRef
51.
Lacy MQ, LaPlant BR, Laumann KM, Kumar S, Gertz MA, Hayman SR, et al. Pomalidomide, bortezomib and dexamethasone (PVD) for patients with relapsed lenalidomide refractory multiple myeloma (MM). Blood. 2014;124:304.
52.
Sonneveld P, Asselbergs E, Zweegman S, van der Holt B, Kersten MJ, Vellenga E, et al. Phase 2 study of carfilzomib, thalidomide, and dexamethasone as induction/consolidation therapy for newly diagnosed multiple myeloma. Blood. 2015;125:449–56.PubMedPubMedCentralCrossRef
53.
Danhof S, Schreder M, Rasche L, Strifler S, Einsele H, Knop S. “Real-life” experience of preapproval carfilzomib-based therapy in myeloma—analysis of cardiac toxicity and predisposing factors. Eur J Haematol. 2015;97:25–32.PubMedCrossRef
54.
Shah JJ, Stadtmauer EA, Abonour R, Cohen AD, Bensinger WI, Gasparetto C, et al. Carfilzomib, pomalidomide, and dexamethasone for relapsed or refractory myeloma. Blood. 2015;126:2284–90.PubMedPubMedCentralCrossRef
55.
Moreau P, Masszi T, Grzasko N, Bahlis NJ, Hansson M, Pour L, et al. Oral ixazomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;374:1621–34.PubMedCrossRef
56.
Lonial S, Richardson PG, San Miguel J, Sonneveld P, Schuster MW, Bladé J, et al. Characterisation of haematological profiles and low risk of thromboembolic events with bortezomib in patients with relapsed multiple myeloma. Br J Haematol. 2008;143:222–9.PubMedCrossRef
57.
Zangari M, Fink L, Zhan F, Tricot G. Low venous thromboembolic risk with bortezomib in multiple myeloma and potential protective effect with thalidomide/lenalidomide-based therapy: review of data from phase 3 trials and studies of novel combination regimens. Clin Lymphoma Myeloma Leuk. 2011;11:228–36.PubMedCrossRef
58.
Pye J, Ardeshirpour F, McCain A, Bellinger DA, Merricks E, Adams J, et al. Proteasome inhibition ablates activation of NF-κB in myocardial reperfusion and reduces reperfusion injury. Am J Physiol Heart Circ Physiol. 2003;284:H919–26.PubMedCrossRef
59.
Stansfield WE, Tang RH, Moss NC, Baldwin AS, Willis MS, Selzman CH. Proteasome inhibition promotes regression of left ventricular hypertrophy. Am J Physiol Heart Circ Physiol. 2008;294:H645–50.PubMedCrossRef
60.
O’Connor OA, Stewart AK, Vallone M, Molineaux CJ, Kunkel LA, Gerecitano JF, et al. A phase 1 dose escalation study of the safety and pharmacokinetics of the novel proteasome inhibitor carfilzomib (PR-171) in patients with hematologic malignancies. Clin Cancer Res. 2009;15:7085–91.PubMedPubMedCentralCrossRef
61.
Badros AZ, Vij R, Martin T, Zonder JA, Kunkel L, Wang Z, et al. Carfilzomib in multiple myeloma patients with renal impairment: pharmacokinetics and safety. Leukemia. 2013;27:1707–14.PubMedPubMedCentralCrossRef
62.
Vij R, Siegel DS, Jagannath S, Jakubowiak AJ, Stewart AK, McDonagh K, et al. An open-label, single-arm, phase 2 study of single-agent carfilzomib in patients with relapsed and/or refractory multiple myeloma who have been previously treated with bortezomib. Br J Haematol. 2012;158:739–48.PubMedPubMedCentralCrossRef
63.
• Atrash S, Tullos A, Panozzo S, Bhutani M, Van Rhee F, Barlogie B, et al. Cardiac complications in relapsed and refractory multiple myeloma patients treated with carfilzomib. Blood Cancer J. 2015;5:e272. This study reports significant cardiovascular adverse events necessitating hospitalization during the first two cycles of therapy with carfilzomib. It also reviews echocardiogram findings before and after treatment as well as BNP measurements.PubMedPubMedCentralCrossRef
64.
Grandin EW, Ky B, Cornell RF, Carver J, Lenihan DJ. Patterns of cardiac toxicity associated with irreversible proteasome inhibition in the treatment of multiple myeloma. J Card Fail. 2015;21:138–44.PubMedCrossRef
65.
Fradley MG, Groarke JD, Laubach J, Alsina M, Lenihan DJ, Cornell RF, et al. Recurrent cardiotoxicity potentiated by the interaction of proteasome inhibitor and immunomodulatory therapy for the treatment of multiple myeloma. Br J Haematol. 2017;23:2147.
66.
Kumar SK, Berdeja JG, Niesvizky R, Lonial S, Laubach JP, Hamadani M, et al. Safety and tolerability of ixazomib, an oral proteasome inhibitor, in combination with lenalidomide and dexamethasone in patients with previously untreated multiple myeloma: an open-label phase 1/2 study. Lancet Oncol. 2014;15:1503–12.PubMedCrossRef
67.
Jouni H, Aubry MC, Lacy MQ, Vincent Rajkumar S, Kumar SK, Frye RL, et al. Ixazomib cardiotoxicity: a possible class effect of proteasome inhibitors. Am J Hematol. 2017;92:220–1.PubMedCrossRef
68.
Mcbride WG. Thalidomide and congenital abnormalities. Lancet. 1961;278:1358.CrossRef
69.
Rajkumar SV, Gertz MA, Lacy MQ, Dispenzieri A, Fonseca R, Geyer SM, et al. Thalidomide as initial therapy for early-stage myeloma. Leukemia. 2003;17:775–9.PubMedCrossRef
70.
Singhal S, Mehta J, Desikan R, Ayers D, Roberson P, Eddlemon P, et al. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med. 1999;341:1565–71.PubMedCrossRef
71.
Kristinsson SY, Fears TR, Gridley G, Turesson I, Mellqvist UH, Bjorkholm M, et al. Deep vein thrombosis after monoclonal gammopathy of undetermined significance and multiple myeloma. Blood. 2008;112:3582–6.PubMedPubMedCentralCrossRef
72.
Osman K, Comenzo R, Rajkumar SV. Deep venous thrombosis and thalidomide therapy for multiple myeloma. N Engl J Med. 2001;344:1951–2.PubMedCrossRef
73.
Palumbo A, Rajkumar SV, Dimopoulos MA, Richardson PG, San Miguel J, Barlogie B, et al. Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia. 2007;22:414–23.PubMedCrossRef
74.
Accaoui El RN, Shamseddeen WA, Taher AT. Thalidomide and thrombosis. A meta-analysis. Thromb Haemost. 2007;97:1031–6.CrossRef
75.
Scarpace S, Hahn T, Roy H, Brown K, Paplham P, Chanan-Khan A, et al. Arterial thrombosis in four patients treated with thalidomide. Leuk Lymphoma. 2009;46:239–42.CrossRef
76.
Goz M, Eren MN, Cakir O. Arterial thrombosis and thalidomide. J Thromb Thrombolysis. 2007;25:224–6.CrossRef
77.
Libourel EJ, Sonneveld P, van der Holt B, de Maat MPM, Leebeek FWG. High incidence of arterial thrombosis in young patients treated for multiple myeloma: results of a prospective cohort study. Blood. 2010;116:22–6.PubMedCrossRef
78.
Bowcock SJ, Rassam SMB, Ward SM, Turner JT, Laffan M. Thromboembolism in patients on thalidomide for myeloma. Hematology. 2002;7:51–3.PubMedCrossRef
79.
Arboscello E, Bellodi A, Passalia C, Spallarossa P, Balleari E, Ponassi I, et al. Thalidomide-induced cardiotoxicity in multiple myeloma patients: an underestimated but clinically relevant issue. J Clin Oncol. 2010;28:e18544.CrossRef
80.
Dimopoulos MA, Chen C, Spencer A, Niesvizky R, Attal M, Stadtmauer EA, et al. Long-term follow-up on overall survival from the MM-009 and MM-010 phase III trials of lenalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma. Leukemia. 2009;23:2147–52.PubMedCrossRef
81.
82.
Mikhael J, Rajkumar V, Roy V, Hayman SR, Fonseca R, Detweiler Short K, et al. Efficacy of pomalidomide plus low-dose dexamethasone in multiple myeloma patients despite previous use of lenalidomide. J Clin Oncol. 2011;29:8067.CrossRef
83.
Lacy MQ, Hayman SR, Gertz MA, Dispenzieri A, Buadi F, Kumar S, et al. Pomalidomide (CC4047) plus low-dose dexamethasone as therapy for relapsed multiple myeloma. J Clin Oncol. 2009;27:5008–14.PubMedCrossRef
84.
Miguel JS, Weisel K, Moreau P, Lacy M, Song K, Delforge M, et al. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013;14:1055–66.CrossRef
85.
Dimopoulos MA, Leleu X, Palumbo A, Moreau P, Delforge M, Cavo M, et al. Expert panel consensus statement on the optimal use of pomalidomide in relapsed and refractory multiple myeloma. Leukemia. 2014;28:1573–85.PubMedPubMedCentralCrossRef
86.
Wei Q, Xia Y. Proteasome inhibition down-regulates endothelial nitric-oxide synthase phosphorylation and function. J Biol Chem. 2006;281:21,652–9.CrossRef
87.
Versari D. Dysregulation of the ubiquitin-proteasome system in human carotid atherosclerosis. Arterioscler Thromb Vasc Biol. 2006;26:2132–9.PubMedCrossRef
88.
Aue G, Nelson Lozier J, Tian X, Cullinane AM, Soto S, Samsel L, et al. Inflammation, TNFα and endothelial dysfunction link lenalidomide to venous thrombosis in chronic lymphocytic leukemia. Am J Hematol. 2011;86:835–40.PubMedPubMedCentralCrossRef
89.
Rosovsky R, Hong F, Tocco D, Connell B, Mitsiades C, Schlossman R, et al. Endothelial stress products and coagulation markers in patients with multiple myeloma treated with lenalidomide plus dexamethasone: an observational study. Br J Haematol. 2013;160:351–8.PubMedCrossRef
90.
Moslehi JJ. Cardiovascular toxic effects of targeted cancer therapies. N Engl J Med. 2016;375:1457–67.PubMedCrossRef
91.
Li W, Garcia D, Cornell RF, Gailani D, Laubach J, Maglio ME, et al. Cardiovascular and thrombotic complications of novel multiple myeloma therapies. JAMA Oncol. 2017;3:980.PubMedCrossRef
92.
Lyman GH, Khorana AA, Falanga A, Clarke-Pearson D, Flowers C, Jahanzeb M, et al. American Society of Clinical Oncology guideline: recommendations for venous thromboembolism prophylaxis and treatment in patients with cancer. J Clin Oncol. 2007;25:5490–505.PubMedCrossRef
93.
Palumbo A, Cavo M, Bringhen S, Zamagni E, Romano A, Patriarca F, et al. Aspirin, warfarin, or enoxaparin thromboprophylaxis in patients with multiple myeloma treated with thalidomide: a phase III, open-label, randomized trial. J Clin Oncol. 2011;29:986–93.PubMedCrossRef
94.
Larocca A, Cavallo F, Bringhen S, Di Raimondo F, Falanga A, Evangelista A, et al. Aspirin or enoxaparin thromboprophylaxis for patients with newly diagnosed multiple myeloma treated with lenalidomide. Blood. 2012;119:933–9.quiz1093PubMedCrossRef
95.
Palumbo A, Rajkumar SV, San Miguel JF, Larocca A, Niesvizky R, Morgan G, et al. 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. J Clin Oncol. 2014;32:587–600.PubMedPubMedCentralCrossRef
96.
Kamat AV. Rivaroxaban is an effective and well tolerated anti thrombotic agent in patients on lenalidomide therapy and in multiple myeloma. Blood. 2014;124:5095.
97.
Meseeha MG, Kolade VO, Attia MN. Partially reversible bortezomib-induced cardiotoxicity: an unusual cause of acute cardiomyopathy. J Community Hosp Intern Med Perspect. 2015;5:28,982.CrossRef
98.
Voortman J, Giaccone G. Severe reversible cardiac failure after bortezomib treatment combined with chemotherapy in a non-small cell lung cancer patient: a case report. BMC Cancer. 2006;6:11.CrossRef
99.
Russell SD, Lyon A, Lenihan DJ, Moreau P, Joshua D, Chng W-J, et al. 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. 2015;126:4250.
100.
Imam F, Al-Harbi NO, Al-Harbi MM, Ansari MA, Almutairi MM, Alshammari M, et al. Apremilast reversed carfilzomib-induced cardiotoxicity through inhibition of oxidative stress, NF-κB and MAPK signaling in rats. Toxicol Mech Methods. 2016;26:700–8.PubMedCrossRef
101.
Imam F, Al-Harbi NO, Al-Harbia MM, Korashy HM, Ansari MA, Sayed-Ahmed MM, et al. Rutin attenuates carfilzomib-induced cardiotoxicity through inhibition of NF-κB, hypertrophic gene expression and oxidative stress. Cardiovasc Toxicol. 2017;17:58–66.PubMedCrossRef
102.
Mikhael J. Management of carfilzomib-associated cardiac adverse events. Clin Lymphoma Myeloma Leuk. 2016;16:241–5.PubMedCrossRef
103.
Koulaouzidis G, Lyon AR. Proteasome inhibitors as a potential cause of heart failure. Heart Fail Clin. 2017;13:289–95.PubMedCrossRef
104.
Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults. J Am Coll Cardiol. 2017.
105.
Metadata
Title
Cardiovascular Complications of Multiple Myeloma Treatment: Evaluation, Management, and Prevention
Authors
Dae Hyun Lee, MD
Michael G. Fradley, MD
Publication date
01-03-2018
Publisher
Springer US
Published in
Current Treatment Options in Cardiovascular Medicine / Issue 3/2018
Print ISSN: 1092-8464
Electronic ISSN: 1534-3189
DOI
https://doi.org/10.1007/s11936-018-0618-y

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