Carfilzomib and dexamethasone maintenance following salvage ASCT in multiple myeloma: A randomised phase 2 trial by the Nordic Myeloma Study Group

Eur J Haematol. 2022 Jan;108(1):34-44. doi: 10.1111/ejh.13709. Epub 2021 Oct 11.

Abstract

Objective: We investigated the efficacy and safety of carfilzomib-containing induction before salvage high-dose melphalan with autologous stem-cell transplantation (salvage ASCT) and maintenance with carfilzomib and dexamethasone after salvage ASCT in multiple myeloma.

Methods: This randomised, open-label, phase 2 trial included patients with first relapse of multiple myeloma after upfront ASCT who were re-induced with four cycles of carfilzomib, cyclophosphamide and dexamethasone. Two months after salvage, ASCT patients were randomised to either observation or maintenance therapy with iv carfilzomib 27 → 56 mg/sqm and p.o. dexamethasone 20 mg every second week. The study enrolled 200 patients of which 168 were randomised to either maintenance with carfilzomib and dexamethasone (n = 82) or observation (n = 86).

Results: Median time to progression (TTP) after randomisation was 25.1 months (22.5-NR) in the carfilzomib-dexamethasone maintenance group and 16.7 months (14.4-21.8) in the control group (HR 0.46, 95% CI 0.30-0.71; P = .0004). The most common adverse events during maintenance were thrombocytopenia, anaemia, hypertension, dyspnoea and bacterial infections.

Conclusion: In summary, maintenance therapy with carfilzomib and dexamethasone after salvage ASCT prolonged TTP with 8 months. The maintenance treatment was in general well-tolerated with manageable toxicity.

Keywords: carfilzomib; induction chemotherapy; maintenance chemotherapy; multiple myeloma; salvage therapy.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor
  • Clinical Decision-Making
  • Dexamethasone / administration & dosage
  • Disease Management
  • Disease Susceptibility
  • Female
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Hematopoietic Stem Cell Transplantation* / methods
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multiple Myeloma / diagnosis
  • Multiple Myeloma / mortality
  • Multiple Myeloma / therapy*
  • Oligopeptides / administration & dosage
  • Prognosis
  • Transplantation, Autologous
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • Oligopeptides
  • carfilzomib
  • Dexamethasone

Grants and funding