Blood Journal
Leading the way in experimental and clinical research in hematology

The role of maintenance thalidomide therapy in multiple myeloma: MRC Myeloma IX results and meta-analysis

  1. Gareth J. Morgan1,*,
  2. Walter M. Gregory2,*,
  3. Faith E. Davies1,
  4. Sue E. Bell2,
  5. Alexander J. Szubert2,
  6. Julia M. Brown2,
  7. Nuria N. Coy2,
  8. Gordon Cook3,
  9. Nigel H. Russell4,
  10. Claudius Rudin5,
  11. Huw Roddie6,
  12. Mark T. Drayson7,
  13. Roger G. Owen3,
  14. Fiona M. Ross8,
  15. Graham H. Jackson9,
  16. J. Anthony Child2, and
  17. on behalf of the National Cancer Research Institute Haematological Oncology Clinical Studies Group
  1. 1Institute of Cancer Research, Royal Marsden Hospital, London, United Kingdom;
  2. 2Clinical Trials Research Unit, University of Leeds, Leeds, United Kingdom;
  3. 3St James's University Hospital, Leeds, United Kingdom;
  4. 4Nottingham University Hospital, Nottingham, United Kingdom;
  5. 5Royal Devon and Exeter Hospital, Exeter, United Kingdom;
  6. 6Western General Hospital, Edinburgh, United Kingdom;
  7. 7University of Birmingham, Birmingham, United Kingdom;
  8. 8Wessex Regional Genetics Laboratory, University of Southampton, Salisbury, United Kingdom; and
  9. 9University of Newcastle, Newcastle-upon-Tyne, United Kingdom

Abstract

Thalidomide maintenance has the potential to modulate residual multiple myeloma (MM) after an initial response. This trial compared the effect of thalidomide maintenance and no maintenance on progression-free survival (PFS) and overall survival (OS) in MM patients. After intensive or nonintensive induction therapy, 820 newly diagnosed MM patients were randomized to open-label thalidomide maintenance until progression, or no maintenance. Interphase FISH (iFISH) analysis was performed at study entry. Median PFS was significantly longer with thalidomide maintenance (log-rank P < .001). Median OS was similar between regimens (log-rank P = .40). Patients with favorable iFISH showed improved PFS (P = .004) and a trend toward a late survival benefit. Patients with adverse iFISH receiving thalidomide showed no significant PFS benefit and worse OS (P = .009). Effective relapse therapy enhanced survival after progression, translating into a significant OS benefit. Meta-analysis of this and other studies show a significant late OS benefit (P < .001, 7-year difference hazard ratio = 12.3; 95% confidence interval, 5.5-19.0). Thalidomide maintenance significantly improves PFS and can be associated with improved OS. iFISH testing is important in assessing the clinical impact of maintenance therapy. Overview analysis demonstrated that thalidomide maintenance was associated with a significant late OS benefit. This trial was registered at www.isrctn.org as #ISRCTN68454111.

  • Submitted June 6, 2011.
  • Accepted October 11, 2011.
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