Clarithromycin added to bortezomib-cyclophosphamide-dexamethasone impairs health-related quality of life in multiple myeloma patients

Eur J Haematol. 2019 Jan;102(1):70-78. doi: 10.1111/ejh.13175. Epub 2018 Oct 29.

Abstract

Objectives: The Danish Myeloma Study Group initiated a randomized, placebo-controlled, double-blinded phase II study to investigate the efficacy of adding clarithromycin to cyclophosphamide-bortezomib-dexamethasone (VCD) induction therapy in transplant eligible, newly diagnosed multiple myeloma patients. The study was prematurely terminated due to severe complications, and no effect of adding clarithromycin was found. The aim of this study was to compare health-related quality of life (HRQoL) between the two groups and to explore the coherence hereof with adverse event (AE) registration by clinicians.

Methods: Patients completed three validated HRQoL questionnaires at inclusion, before cyclophosphamide priming, and two months after high-dose therapy (HDT). The mean score difference was interpreted by clinically relevant differences between groups. Spearman's correlation analysis was used to compare patient-reported toxicities with AEs.

Results: Of 58 included patients, 55 participated in the HRQoL reporting. Before cyclophosphamide priming, patients in the clarithromycin group reported clinically relevant reduced HRQoL for eleven domains with persistent reduction in four domains two months after HDT. Poor correlation between patient-reported toxicities and clinician-reported AEs was observed.

Conclusions: Despite the premature study termination, our data demonstrate impaired HRQoL when clarithromycin was added to the VCD regimen. We found clear underreporting of toxicities by clinicians. ClinicalTrials.gov number NCT02573935.

Keywords: clinical trials; multiple myeloma; quality of life; transplantation.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bortezomib / administration & dosage
  • Clarithromycin / administration & dosage
  • Clinical Protocols
  • Cyclophosphamide / administration & dosage
  • Denmark / epidemiology
  • Dexamethasone / administration & dosage
  • Female
  • Humans
  • Induction Chemotherapy
  • Male
  • Middle Aged
  • Multiple Myeloma / diagnosis
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / mortality
  • Neoplasm Staging
  • Quality of Life*
  • Treatment Outcome

Substances

  • Bortezomib
  • Dexamethasone
  • Cyclophosphamide
  • Clarithromycin

Associated data

  • ClinicalTrials.gov/NCT02573935