Evaluation of Cardiovascular Toxicity Associated with Treatments Containing Proteasome Inhibitors in Multiple Myeloma Therapy

  • Andrea Iannaccone
  • G. Bruno
  • A. Ravera
  • F. Gay
  • M. Salvini
  • S. Bringhen
  • L. Sabia
  • E. Avenatti
  • F. Veglio
  • A. Milan
Original Article



Recently new treatment options have substantially increased survival for patients with relapsed and/or refractory multiple myeloma (RRMM). Among these, proteasome inhibitors (PI), such as bortezomib and carfilzomib, offer high response rate and prolonged survival. These agents are generally well tolerated but demonstrated a significant cardiovascular toxicity, mostly for regimen containing carfilzomib.


To assess the cardiovascular damage in patients treated with PI for RRMM.


28 consecutive subjects treated with PI for RRMM were evaluated and compared with a population of 22 control (Con) subjects, matched for age, sex and mean 24 h blood pressure (24hMBP). All individuals underwent trans-thoracic echocardiography, ambulatory blood pressure monitoring and pulse wave velocity (PVW) study.


PI patients did not have significant differences in blood pressure load and PWV compared to controls. Among echocardiographic parameters, the global longitudinal strain (GLS) was significantly decreased in PI subjects (p = 0.02). The GLS was significantly lower also considering only patients treated with carfilzomib. Moreover, among carfilzomib patients, we found increase values of left ventricle mass indexed by BSA (LVMi; p = 0.047). After correction for age, sex, BSA, 24hMBP and morphological and functional parameters of LV, treatment with PI and carfilzomib were significantly associated with GLS (p = 0.01; p = 0.036, respectively).


PI treatment is associated with subclinical LV dysfunction in patients with RRMM compared to controls, as demonstrated by lower GLS values. These results are confirmed also considering patients treated with carfilzomib. Moreover, in this subgroup of patients, the LVMi is also increased, suggesting higher cardiotoxicity with this treatment.


Cardiovascular toxicity Global longitudinal strain Multiple myeloma Proteasome inhibitors Carfilzomib 


Compliance with Ethical Standards

Conflict of interest

The authors have no conflicts of interest. No external funding was used in the production of this work.

Ethical approval

The study was approved by the ethics committees of our Institution and all procedures performed in studies involving human participants were in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

All participants provided written informed consent.

Supplementary material

40292_2018_256_MOESM1_ESM.docx (23 kb)
Supplementary material 1 (DOCX 23 kb)


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Andrea Iannaccone
    • 1
  • G. Bruno
    • 1
  • A. Ravera
    • 1
  • F. Gay
    • 2
  • M. Salvini
    • 2
  • S. Bringhen
    • 2
  • L. Sabia
    • 1
  • E. Avenatti
    • 1
  • F. Veglio
    • 1
  • A. Milan
    • 1
  1. 1.Hypertension Unit, Division of Internal Medicine, Department of Medical Sciences, University Hospital “Città della Salute e della Scienza”University of TorinoTurinItaly
  2. 2.Myeloma Unit, Division of Hematology, Department of Molecular Biotechnology and Health Sciences, University Hospital ‘Città della Salute e della Scienza di Torino’University of TorinoTurinItaly

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