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Updated: Feb 5, 2026

Establishment of a Human Multiple Myeloma Xenograft Model in the Chicken to Study Tumor Growth, Invasion and Angiogenesis
Published on: May 1, 2015
Bortezomib-based Chemotherapy for Multiple Myeloma Patients Without Comorbid Cardiovascular Disease Shows No
Stephen B Heitner1, Jessica Minnier2, Aynun Naher1
1Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR.
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.
Insights
Bortezomib-based chemotherapy for multiple myeloma did not show evidence of cardiotoxicity in patients without prior cardiovascular disease. Comprehensive cardiac evaluations found no cumulative or transient myocardial dysfunction, indicating cardiovascular safety.
Area of Science:
- Cardiology
- Oncology
- Pharmacology
Background:
- Proteasome inhibitors, like bortezomib, treat multiple myeloma by inducing proteotoxic stress, leading to cancer cell death.
- Concerns exist regarding potential off-target cardiotoxicity from bortezomib, necessitating investigation into its cardiovascular effects.
Purpose of the Study:
- To assess for evidence of myocardial dysfunction associated with bortezomib-based chemotherapy in multiple myeloma patients.
- To evaluate both subclinical and transient cardiotoxicity using advanced cardiac imaging and biomarkers.
Main Methods:
- Eleven patients (18-70 years) without significant cardiovascular disease received bortezomib chemotherapy.
- Evaluations included echocardiography (assessing global longitudinal strain - GLS), serum biomarkers, and cardiac MRI before and after treatment.
- Global longitudinal strain (GLS) was the primary method for detecting subclinical myocardial dysfunction.
Main Results:
- No significant cumulative or transient myocardial dysfunction was detected by echocardiography (GLS, LVEF) or cardiac MRI.
- Average change in absolute GLS was -1.17 (P=.064), and LVEF showed no significant changes (ΔLVEF, -2.17%; P=.15).
- Cardiac MRI confirmed no structural or functional changes, and serum biomarkers remained stable.
Conclusions:
- Bortezomib-based chemotherapy did not induce cardiotoxicity in this cohort of patients without pre-existing cardiovascular disease.
- Intensive multimodal cardiac assessments revealed no cumulative or transient alterations, supporting the cardiovascular safety of bortezomib.
- Findings suggest bortezomib can be safely administered from a cardiovascular perspective in eligible multiple myeloma patients.
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