Bortezomib-based Chemotherapy for Multiple Myeloma Patients Without Comorbid Cardiovascular Disease Shows No Cardiotoxicity

被引:2
作者
Heitner, Stephen B. [1 ]
Minnier, Jessica [1 ,2 ]
Naher, Aynun [1 ]
Van Woerkom, Ryan C. [1 ]
Ritts, Alexandra [1 ]
Ferencik, Maros [1 ]
Broberg, Craig [1 ]
Medvedova, Eva [2 ]
Silbermann, Rebecca [2 ]
Scott, Emma C. [2 ]
机构
[1] Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, UHN62, Portland, OR 97239 USA
[2] Oregon Hlth & Sci Univ, OHSU PSU Sch Publ Hlth, Portland, OR 97201 USA
关键词
Bortezomib; Cardiooncology; Cardiotoxicity; Multiple myeloma; SINGLE-AGENT CARFILZOMIB; ANTHRACYCLINE CARDIOTOXICITY; EUROPEAN ASSOCIATION; AMERICAN SOCIETY; EXPERT CONSENSUS; CARDIAC-FAILURE; CANCER-THERAPY; ADULT PATIENTS; OPEN-LABEL; DEXAMETHASONE;
D O I
10.1016/j.clml.2018.08.004
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Bortezomib has been used to treat multiple myeloma; however, the potential cardiotoxicity has never been prospectively evaluated. We studied 11 patients without cardiovascular comorbidities using strain echocardiography, cardiac magnetic resonance imaging, and serum biomarkers. We did not observe cumulative or transient alterations in these cardiac metrics, suggesting that bortezomib is safe from a cardiovascular standpoint for patients free of cardiovascular disease. Background: Proteasome inhibitors used in the treatment of multiple myeloma act primarily through the disruption of intrinsic cellular protein quality maintenance, resulting in proteotoxic stress, cellular dysfunction, and, ultimately, cell death. We assessed whether evidence has shown off-target myocardial dysfunction related to the administration of bortezomib-based chemotherapy for multiple myeloma. Patients and Methods: Patients aged 18 to 70 years who were free of significant cardiovascular disease were included. They underwent evaluations before and after each dose of bortezomib to assess for clinical, subclinical, and transient cardiotoxicity using echocardiography and serum biomarker measurement. Cardiac magnetic resonance imaging was performed at 3 separately defined intervals. The primary modality for determining subclinical myocardial dysfunction was echocardiographic assessment of the global longitudinal strain (GLS). Results: Eleven patients (7 men) with an average age of 55 years were included. No evidence of cumulative myocardial dysfunction was found using echocardiographic markers, primarily GLS (average change in absolute GLS, -1.17; P =.064). Additionally, no echocardiographic evidence of transient cardiotoxicity was found. The left ventricular ejection fraction (LVEF) also did not show any significant changes (Delta LVEF, -2.17%; P =.15). Magnetic resonance imaging confirmed no changes in structure or function (Delta LVEF, -2.6%; P =.54) and extracellular volume fraction (Delta = 2%; P =.46). The serum biomarker levels also did not change significantly over time. Conclusion: We did not observe cardiotoxicity from bortezomib-based chemotherapy despite very intensive evaluation with multiple modalities. Neither cumulative nor transient alterations were found in our metrics, suggesting that bortezomib is safe from a cardiovascular standpoint for patients free of cardiovascular disease. (C) 2018 Elsevier Inc. All rights reserved.
引用
收藏
页码:796 / 802
页数:7
相关论文
共 28 条
  • [1] The Relationship Between Serum Markers of Collagen Turnover and Cardiovascular Outcome in the Elderly The Cardiovascular Health Study
    Barasch, Eddy
    Gottdiener, John S.
    Aurigemma, Gerard
    Kitzman, Dalane W.
    Han, Jing
    Kop, Willem J.
    Tracy, Russell P.
    [J]. CIRCULATION-HEART FAILURE, 2011, 4 (06) : 733 - 739
  • [2] Prevention of high-dose chemotherapy-induced cardiotoxicity in high-risk patients by angiotensin-converting enzyme inhibition
    Cardinale, Daniela
    Colombo, Alessandro
    Sandri, Maria T.
    Lamantia, Giuseppina
    Colombo, Nicola
    Civelli, Maurizio
    Martinelli, Giovanni
    Veglia, Fabrizio
    Fiorentini, Cesare
    Cipolla, Carlo M.
    [J]. CIRCULATION, 2006, 114 (23) : 2474 - 2481
  • [3] Carfilzomib or bortezomib in relapsed or refractory multiple myeloma (ENDEAVOR): an interim overall survival analysis of an open-label, randomised, phase 3 trial
    Dimopoulos, Meletios A.
    Goldschmidt, Hartmut
    Niesvizky, Ruben
    Joshua, Douglas
    Chng, Wee-Joo
    Oriol, Albert
    Orlowski, Robert Z.
    Ludwig, Heinz
    Facon, Thierry
    Hajek, Roman
    Weisel, Katja
    Hungria, Vania
    Minuk, Leonard
    Feng, Shibao
    Zahlten-Kumeli, Anita
    Kimball, Amy S.
    Moreau, Philippe
    [J]. LANCET ONCOLOGY, 2017, 18 (10) : 1327 - 1337
  • [4] Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study
    Dimopoulos, Meletios A.
    Moreau, Philippe
    Palumbo, Antonio
    Joshua, Douglas
    Pour, Ludek
    Hajek, Roman
    Facon, Thierry
    Ludwig, Heinz
    Oriol, Albert
    Goldschmidt, Hartmut
    Rosinol, Laura
    Straub, Jan
    Suvorov, Aleksandr
    Araujo, Carla
    Rimashevskaya, Elena
    Pika, Tomas
    Gaidano, Gianluca
    Weisel, Katja
    Goranova-Marinova, Vesselina
    Schwarer, Anthony
    Minuk, Leonard
    Masszi, Tamas
    Karamanesht, Ievgenii
    Offidani, Massimo
    Hungria, Vania
    Spencer, Andrew
    Orlowski, Robert Z.
    Gillenwater, Heidi H.
    Mohamed, Nehal
    Feng, Shibao
    Chng, Wee-Joo
    [J]. LANCET ONCOLOGY, 2016, 17 (01) : 27 - 38
  • [5] Acute cardiac functional and morphological changes after Anthracycline infusions in children
    Ganame, Javier
    Claus, Piet
    Eyskens, Benedicte
    Uyttebroeck, Anne
    Renard, Marleen
    D'hooge, Jan
    Gewillig, Marc
    Bijnens, Bart
    Sutherland, George R.
    Mertens, Luc
    [J]. AMERICAN JOURNAL OF CARDIOLOGY, 2007, 99 (07) : 974 - 977
  • [6] Acute severe cardiac failure in a myeloma patient due to proteasome inhibitor bortezomib
    Hacihanefioglu, Abdullah
    Tarkun, Pinar
    Gonullu, Emel
    [J]. INTERNATIONAL JOURNAL OF HEMATOLOGY, 2008, 88 (02) : 219 - 222
  • [7] Use of myocardial deformation imaging to detect preclinical myocardial dysfunction before conventional measures in patients undergoing breast cancer treatment with trastuzumab
    Hare, James L.
    Brown, Joseph K.
    Leano, Rodel
    Jenkins, Carly
    Woodward, Natasha
    Marwick, Thomas H.
    [J]. AMERICAN HEART JOURNAL, 2009, 158 (02) : 294 - 301
  • [8] Functional monitoring of anthracycline cardiotoxicity: a prospective, blinded, long-term observational study of outcome in 120 patients
    Jensen, BV
    Skovsgaard, T
    Nielsen, SL
    [J]. ANNALS OF ONCOLOGY, 2002, 13 (05) : 699 - 709
  • [9] Strain Rate Imaging Detects Early Cardiac Effects of Pegylated Liposomal Doxorubicin as Adjuvant Therapy in Elderly Patients with Breast Cancer
    Jurcut, Ruxandra
    Wildiers, Hans
    Ganame, Javier
    D'hooge, Jan
    De Backer, Julie
    Denys, Hannelore
    Paridaens, Robert
    Rademakers, Frank
    Voigt, Jens-Uwe
    [J]. JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY, 2008, 21 (12) : 1283 - 1289
  • [10] Cardiac Event Rates in Patients with Newly Diagnosed and Relapsed Multiple Myeloma in US Clinical Practice
    Kistler, Kristin D.
    Rajangam, Kanya
    Faich, Gerald
    Lanes, Stephan
    [J]. BLOOD, 2012, 120 (21)