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

Stephen B. Heitner, Jessica Minnier, Aynun Naher, Ryan C. Van Woerkom, Alexandra Ritts, Maros Ferencik, Craig Broberg, Eva Medvedova, Rebecca Silbermann, Emma C. 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)
Pages (from-to)796-802
Number of pages7
JournalClinical Lymphoma, Myeloma and Leukemia
Volume18
Issue number12
DOIs
Publication statusPublished - Dec 2018
Externally publishedYes

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Keywords

  • Bortezomib
  • Cardiooncology
  • Cardiotoxicity
  • Multiple myeloma

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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