The impact of cytogenetics on duration of response and overall survival in patients with relapsed multiple myeloma (long-term follow-up results from BSBMT/UKMF Myeloma X Relapse [Intensive]): a randomised, open-label, phase 3 trial

Research output: Contribution to journalArticlepeer-review

Authors

External organisations

  • University of Leeds
  • Leeds Teaching Hospitals NHS Trust
  • Nottingham City Hospitals
  • Barts and The London NHS Trust
  • Sheffield Teaching Hospitals NHS Foundation Trust
  • Ipswich Hospital NHS Trust
  • Manchester Royal Infirmary
  • Medway Maritime Hospital
  • University Hospital Southampton NHS Foundation Trust
  • University College London
  • Manchester Academic Health Science Centre
  • Plymouth Hospitals Trust
  • University of Bristol
  • Queen's University, Belfast
  • Heart of England NHS Foundation Trust
  • St. George's Healthcare National Health Service Trust

Abstract

The Myeloma X trial (ISCRTN60123120) registered patients with relapsed multiple myeloma. Participants were randomised between salvage autologous stem cell transplantation (ASCT) or weekly cyclophosphamide following re-induction therapy. Cytogenetic analysis performed at trial registration defined t(4;14), t(14;16) and del(17p) as high-risk. The effect of cytogenetics on time to progression (TTP) and overall survival was investigated. At 76 months median follow-up, ASCT improved TTP compared to cyclophosphamide (19 months (95% confidence interval [95% CI] 16–26) vs. 11 months (9–12), hazard ratio [HR]: 0·40, 95% CI: 0·29–0·56, P < 0·001), on which the presence of any single high-risk lesion had a detrimental impact [likelihood ratio test (LRT): P = 0·011]. ASCT also improved OS [67 months (95% CI 59-not reached) vs. 55 months (44–67), HR: 0·64, 95% CI: 0·42–0·99, = 0·0435], with evidence of a detrimental impact with MYC rearrangement (LRT: P = 0·021). Twenty-one (24·7%) cyclophosphamide patients received an ASCT post-trial, median OS was not reached (95% CI: 39-not reached) for these participants compared to 31 months (22–39), in those who did not receive a post-trial ASCT. The analysis further supports the benefit of salvage ASCT, which may still be beneficial after second relapse in surviving patients. There is evidence that this benefit reduces in cytogenetic high-risk patients, highlighting the need for targeted study in this patient group.

Details

Original languageEnglish
Pages (from-to)450-467
Number of pages18
JournalBritish Journal of Haematology
Volume185
Issue number3
Early online date6 Feb 2019
Publication statusPublished - May 2019

Keywords

  • cytogenetics, duration of response, overall survival, relapsed multiple myeloma, salvage ASCT

ASJC Scopus subject areas