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Lancet Oncol. 2014 Jul;15(8):874-85. doi: 10.1016/S1470-2045(14)70245-1. Epub 2014 Jun 16.

High-dose chemotherapy plus autologous stem-cell transplantation as consolidation therapy in patients with relapsed multiple myeloma after previous autologous stem-cell transplantation (NCRI Myeloma X Relapse [Intensive trial]): a randomised, open-label, phase 3 trial.

Author information

1
St James's Institute of Oncology, Leeds Teaching Hospitals NHS Trust and University of Leeds, Leeds, UK. Electronic address: g.cook@leeds.ac.uk.
2
Centre for Clinical Haematology, Nottingham University Hospitals NHS Trust, Nottingham, UK.
3
Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.
4
Department of Haematology, Barts and The London NHS Trust, London, UK.
5
Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust and University of Sheffield, Sheffield, UK.
6
Mid Yorkshire Hospitals NHS Trust, Wakefield, UK.
7
St James's Institute of Oncology, Leeds Teaching Hospitals NHS Trust and University of Leeds, Leeds, UK.
8
Department of Haematology, University College Hospital, London, UK.
9
Department of Haematology, The Christie NHS Foundation Trust, Manchester, UK.
10
Department of Haematology, Plymouth Hospitals NHS Trust, Plymouth, UK.
11
Department of Haematology, United Bristol Hospitals NHS Trust, Bristol, UK.
12
Haematology Malignancy Diagnostic Service, Leeds Teaching Hospitals NHS Trust and University of Leeds, Leeds, UK.
13
University of Birmingham, Birmingham, UK.
14
Queen's University, Belfast, UK.

Erratum in

  • Lancet Oncol. 2014 Aug;15(9):e365. Dosage error in article text.

Abstract

BACKGROUND:

Relapsed multiple myeloma has no standard treatment, and the role of autologous stem-cell transplantation (ASCT) has not been fully defined. We aimed to compare high-dose melphalan plus salvage ASCT with cyclophosphamide in patients with relapsed multiple myeloma who had previously undergone ASCT.

METHODS:

This multicentre, randomised, open-label, phase 3 study recruited patients aged at least 18 years with multiple myeloma who needed treatment for first progressive or relapsed disease at least 18 months after a previous ASCT from 51 centres across the UK. Before randomisation, eligible patients received bortezomib, doxorubicin, and dexamethasone (PAD) induction therapy and then underwent peripheral blood stem-cell mobilisation and harvesting if applicable. Eligible patients (with adequate stem-cell harvest) were randomly assigned (1:1), using an automated telephone randomisation line, to either high-dose melphalan 200 mg/m(2) plus salvage ASCT or oral cyclophosphamide (400mg/m(2) per week for 12 weeks). Randomisation was stratified by length of first remission or plateau and response to PAD re-induction therapy. The primary endpoint was time to disease progression, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00747877, and EudraCT, number 2006-005890-24.

FINDINGS:

Between April 16, 2008, and Nov 19, 2012, 297 patients were registered, of whom 293 received PAD re-induction therapy. Between Aug 26, 2008, and Nov 16, 2012, 174 patients with sufficient PBSCs were randomised to salvage ASCT (n=89) or cyclophosphamide (n=85). After a median follow-up of 31 months (IQR 19-42), median time to progression was significantly longer in the salvage ASCT than in the cyclophosphamide group (19 months [95% CI 16-25] vs 11 months [9-12]; hazard ratio 0·36 [95% CI 0·25-0·53]; p<0·0001). Frequently reported (in >10% of patients) grade 3-4 adverse events with PAD induction, salvage ASCT, and cyclophosphamide were: neutropenia (125 [43%] of 293 patients after PAD, and 63 [76%] of 83 patients in the salvage ASCT group vs 11 [13%] of 84 patients in the cyclophosphamide group), thrombocytopenia (150 [51%] after PAD, and 60 [72%] vs four [5%], respectively), and peripheral neuropathy (35 [12%] after PAD, and none vs none, respectively).

INTERPRETATION:

This study provides evidence for the improved efficacy of high-dose melphalan plus salvage ASCT when compared with cyclophosphamide in patients with relapsed multiple myeloma eligible for intensive therapy, which might help to guide clinical decisions regarding the management of such patients.

FUNDING:

Cancer Research UK.

PMID:
24948586
DOI:
10.1016/S1470-2045(14)70245-1
[Indexed for MEDLINE]

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