Irreversible proteasome inhibition with carfilzomib as first line therapy in patients with newly diagnosed multiple myeloma: Early in vivo cardiovascular effects

Eur J Pharmacol. 2018 Nov 5:838:85-90. doi: 10.1016/j.ejphar.2018.09.014. Epub 2018 Sep 7.

Abstract

Patients who experienced cardiovascular side effects during cancer therapy with carfilzomib for multiple myeloma had relapsed multiple myeloma, so have be previously treated with other cancer therapies. The present is a single center cohort study to evaluate early cardiovascular effects of administration of irreversible proteasome inhibitor carfilzomib in naïve patients. We included 24 patients and collected cardiovascular side effects, echocardiographic parameters and endothelial function at baseline and after 4 cycles. At early follow up we observed increase in blood arterial pressure values (mean change in systolic pressure of 10 mmHg (P-value < 0.01; diastolic arterial pressure and mean arterial pressure of 3.3 mmHg and 5.4 mmHg, both P-value < 0.01). Reactive hyperemia PAT index was reduced in the whole cohort by a mean of 0.46 points (P-value < 0.01); diastolic function was changed: E-wave-deceleration-time (EDT) was reduced by 49,96 ± 31 ms, P-value < 0.05 and early diastolic tissue Doppler velocity (e') by a mean value of 1.46 cm/s, P - value 0.04. At early follow up we did not observe events of grade 3 or 4. We observe correlation between events and endothelial dysfunction at baseline and age (OR 1.9, CI 95% 0.05-5.804, P- value: 0.038 for RHI<1.67; OR 1,4, CI 95%0.99-2.56, P- value: 0.04 for age). Our results suggest that therapy with carfilzomib when used as first line therapy is responsible for increase in systemic blood pressure, alteration of endothelium-mediated vascular dilatation and early myocardial diastolic dysfunction.

Keywords: Cancer therapy; Cardiovascular effects; Carfilzomib; EndoPAT.

MeSH terms

  • Age Factors
  • Antineoplastic Agents / adverse effects*
  • Blood Pressure / drug effects
  • Cohort Studies
  • Diastole / drug effects
  • Echocardiography, Doppler
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiopathology
  • Female
  • Heart / diagnostic imaging
  • Heart / drug effects
  • Heart / physiopathology
  • Humans
  • Hyperemia / chemically induced
  • Hyperemia / diagnostic imaging
  • Hyperemia / epidemiology
  • Hyperemia / physiopathology
  • Male
  • Middle Aged
  • Multiple Myeloma / drug therapy*
  • Oligopeptides / adverse effects*
  • Proteasome Inhibitors / adverse effects*
  • Treatment Outcome
  • Vasodilation / drug effects

Substances

  • Antineoplastic Agents
  • Oligopeptides
  • Proteasome Inhibitors
  • carfilzomib