Format

Send to

Choose Destination
Br J Haematol. 2019 May;185(3):450-467. doi: 10.1111/bjh.15782. Epub 2019 Feb 6.

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.

Author information

1
Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
2
Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.
3
HMDS, Leeds Teaching Hospitals Trust, Leeds, UK.
4
Mid-Yorkshire NHS Trust, Wakefield, UK.
5
Department of Haematology, Centre for Clinical Haematology, Nottingham City Hospitals, Nottingham, UK.
6
Department of Haematology, Barts & The London NHS Trust, London, UK.
7
Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
8
Ipswich Hospital NHS Trust, Ipswich, UK.
9
Department of Haematology, Manchester Royal Infirmary, Manchester, UK.
10
Medway Maritime Hospital, Kent, UK.
11
University Hospital Southampton NHS Foundation, Southampton, UK.
12
Department of Haematology, University College Hospital, London, UK.
13
Department of Haematology, The Christie NHS Foundation Trust, Manchester, UK.
14
Department of Haematology, Plymouth Hospitals Trust, Plymouth, UK.
15
Department of Haematology, University Hospitals Bristol NHS Trust, Bristol, UK.
16
Department of Haematology, Heart of England NHS Trust, Birmingham, UK.
17
University of Birmingham, Birmingham, UK.
18
Queen's University, Belfast, UK.

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, P = 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.

KEYWORDS:

cytogenetics; duration of response; overall survival; relapsed multiple myeloma; salvage ASCT

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center