The role of maintenance thalidomide therapy in multiple myeloma: MRC Myeloma IX results and meta-analysis.
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.
Institute of Cancer Research, Royal Marsden Hospital, London, United Kingdom. gareth.morgan@icr.ac.uk
Gareth J
GJ
Morgan
Walter M
WM
Gregory
Faith E
FE
Davies
Sue E
SE
Bell
Alexander J
AJ
Szubert
Julia M
JM
Brown
Nuria N
NN
Coy
Gordon
G
Cook
Nigel H
NH
Russell
Claudius
C
Rudin
Huw
H
Roddie
Mark T
MT
Drayson
Roger G
RG
Owen
Fiona M
FM
Ross
Graham H
GH
Jackson
J Anthony
JA
Child
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D060046:Maintenance Chemotherapy; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality*; D015996:Survival Rate; D013792:Thalidomide / Q000627:therapeutic use*; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D013792:Thalidomide