A low serum level of soluble tumor necrosis factor receptor p55 predicts response to thalidomide in advanced multiple myeloma.
OBJECTIVE
Thalidomide modulates the production of tumor necrosis factor (TNF-alpha). Soluble TNF receptors, TNFR p55 and TNFR p75, modify TNF-alpha activity. In this study, we explored the relation between soluble TNF receptors and outcome in patients with advanced multiple myeloma treated with thalidomide.


METHODS
The levels of soluble TNF receptor p55 and p75 were assessed in serum from 34 myeloma patients with relapsed or refractory disease before starting thalidomide treatment. Serial measurements were performed for 16 patients in serum collected during treatment.


RESULTS
The pre-treatment serum level of soluble TNFR p55 in thalidomide responders was significantly lower than that in non-responders (median 1.75 ng/mL (range 1.19-2.84) vs. 2.79 ng/mL (1.36-5.51), p=0.004). The levels of p55 declined significantly during treatment. The levels of p75 showed the same pattern as p55, but the differences were not significant. The median survival of myeloma patients with pre-treatment levels of p55 < 2.79 ng/mL was 404 days; the median survival of patients with pre-treatment levels >or= 2.79 ng/mL was shorter (65 days, log-rank test p=0.02).


CONCLUSIONS
We conclude that soluble TNFR p55 is an adverse prognostic factor in myeloma patients with relapsed or refractory disease treated with thalidomide. Patients with a low pre-treatment level of this receptor have a better response rate and a longer overall survival.
Brenne
Anne-Tove
AT
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, MTFS, N-7489 Trondheim, Norway. anne-tove.brenne@medisin.ntnu.no
Romstad
Lene Hejna
LH
Gimsing
Peter
P
Juliusson
Gunnar
G
Turesson
Ingemar
I
Romundstad
Pål
P
Borset
Magne
M
Sundan
Anders
A
Waage
Anders
A
D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy*; D011379:Prognosis; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood; D015996:Survival Rate; D013792:Thalidomide / Q000627:therapeutic use*
D007166:Immunosuppressive Agents; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D013792:Thalidomide