A retrospective analysis of 3954 patients in phase 2/3 trials of bortezomib for the treatment of multiple myeloma: towards providing a benchmark for the cardiac safety profile of proteasome inhibition in multiple myeloma

Br J Haematol. 2017 Aug;178(4):547-560. doi: 10.1111/bjh.14708. Epub 2017 May 3.

Abstract

This retrospective analysis aimed to establish the overall cardiac safety profile of bortezomib using patient-level data from one phase 2 and seven phase 3 studies in previously untreated and relapsed/refractory multiple myeloma (MM). Seven clinically relevant primary [congestive heart failure (CHF), arrhythmias, ischaemic heart disease (IHD), cardiac death] and secondary (hypertension, dyspnoea, oedema) cardiac endpoints were defined based on MedDRA v16.0 preferred terms. 2509 bortezomib-treated patients and 1445 patients in non-bortezomib-based control arms were included. The incidence of grade ≥3 CHF was 1·3-4·0% in studies in relapsed/refractory MM and 1·2-4·7% in previously untreated MM (2·0-7·6% all grades), with no significant differences between bortezomib- and non-bortezomib-based arms in comparative studies. Incidences of arrhythmias (1·3-5·9% grade ≥2; 0·6-4·1% grade ≥3), IHD (1·2-2·9% all grades; 0·4-2·7% grade ≥3) and cardiac death (0-1·4%) were low, with no differences between bortezomib-based and non-bortezomib-based arms. Higher rates of oedema (mostly grade 1/2) were seen in bortezomib-based versus non-bortezomib-based arms in one study and a pooled transplant study analysis. Logistic regression analyses of comparative studies showed no impact on cardiac risk with bortezomib-based versus non-bortezomib-based treatment. Bortezomib-based treatment was associated with low incidences of cardiac events.

Keywords: bortezomib; cardiac; cardio-oncology; multiple myeloma.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Benchmarking
  • Bortezomib / adverse effects*
  • Bortezomib / therapeutic use
  • Cardiovascular Diseases / chemically induced*
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Dyspnea / chemically induced
  • Heart Failure / chemically induced
  • Humans
  • Multiple Myeloma / drug therapy*
  • Proteasome Inhibitors / adverse effects*
  • Proteasome Inhibitors / therapeutic use
  • Retrospective Studies
  • Risk Factors

Substances

  • Antineoplastic Agents
  • Proteasome Inhibitors
  • Bortezomib