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

Stephen Heitner, Jessica Minnier, Aynun Naher, Ryan Van Woerkem, Alexandra Ritts, Maros Ferencik, Craig Broberg, Eva Medvedova, Rebecca Silbermann, Emma Scott

Research output: Contribution to journalArticle

Abstract

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 (ΔLVEF, −2.17%; P =.15). Magnetic resonance imaging confirmed no changes in structure or function (ΔLVEF, −2.6%; P =.54) and extracellular volume fraction (Δ = 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.

Original languageEnglish (US)
JournalClinical Lymphoma, Myeloma and Leukemia
DOIs
StateAccepted/In press - Jan 1 2018

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Multiple Myeloma
Cardiovascular Diseases
Drug Therapy
Stroke Volume
Biomarkers
Magnetic Resonance Imaging
Echocardiography
Serum
Proteasome Inhibitors
Cardiotoxicity
Bortezomib
Comorbidity
Cell Death
Maintenance
Proteins

Keywords

  • Bortezomib
  • Cardiooncology
  • Cardiotoxicity
  • Multiple myeloma

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Bortezomib-based Chemotherapy for Multiple Myeloma Patients Without Comorbid Cardiovascular Disease Shows No Cardiotoxicity. / Heitner, Stephen; Minnier, Jessica; Naher, Aynun; Van Woerkem, Ryan; Ritts, Alexandra; Ferencik, Maros; Broberg, Craig; Medvedova, Eva; Silbermann, Rebecca; Scott, Emma.

In: Clinical Lymphoma, Myeloma and Leukemia, 01.01.2018.

Research output: Contribution to journalArticle

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title = "Bortezomib-based Chemotherapy for Multiple Myeloma Patients Without Comorbid Cardiovascular Disease Shows No Cardiotoxicity",
abstract = "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 (ΔLVEF, −2.17{\%}; P =.15). Magnetic resonance imaging confirmed no changes in structure or function (ΔLVEF, −2.6{\%}; P =.54) and extracellular volume fraction (Δ = 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.",
keywords = "Bortezomib, Cardiooncology, Cardiotoxicity, Multiple myeloma",
author = "Stephen Heitner and Jessica Minnier and Aynun Naher and {Van Woerkem}, Ryan and Alexandra Ritts and Maros Ferencik and Craig Broberg and Eva Medvedova and Rebecca Silbermann and Emma Scott",
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T1 - Bortezomib-based Chemotherapy for Multiple Myeloma Patients Without Comorbid Cardiovascular Disease Shows No Cardiotoxicity

AU - Heitner, Stephen

AU - Minnier, Jessica

AU - Naher, Aynun

AU - Van Woerkem, Ryan

AU - Ritts, Alexandra

AU - Ferencik, Maros

AU - Broberg, Craig

AU - Medvedova, Eva

AU - Silbermann, Rebecca

AU - Scott, Emma

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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 (ΔLVEF, −2.17%; P =.15). Magnetic resonance imaging confirmed no changes in structure or function (ΔLVEF, −2.6%; P =.54) and extracellular volume fraction (Δ = 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.

AB - 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 (ΔLVEF, −2.17%; P =.15). Magnetic resonance imaging confirmed no changes in structure or function (ΔLVEF, −2.6%; P =.54) and extracellular volume fraction (Δ = 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.

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