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Blood, 15 September 2002, Vol. 100, No. 6, pp. 2263-2265
BRIEF REPORT
Polymorphisms of the tumor necrosis factor- gene promoter
predict for outcome after thalidomide therapy in relapsed and
refractory multiple myeloma
Kai Neben,
Joannis Mytilineos,
Thomas M. Moehler,
Astrid Preiss,
Alwin Kraemer,
Anthony D. Ho,
Gerhard Opelz, and
Hartmut Goldschmidt
From the Department of Internal Medicine V and
Department of Transplantation Immunology, University of Heidelberg,
Germany.
Thalidomide (Thal) is a drug with antiangiogenic,
anti-inflammatory, and immunomodulatory properties that was found to
inhibit the production of tumor necrosis factor- (TNF-) in vitro.
We studied single nucleotide polymorphisms at positions  308 and 238
of the TNF- gene promoter and measured the corresponding TNF-
cytokine levels in 81 patients (pts) with refractory and relapsed
multiple myeloma (MM) who were treated with Thal. In myeloma pts
carrying the TNF-238A allele (n = 8), we found a correlation with
higher pretreatment TNF- levels in peripheral blood
(P = .047). After Thal administration, this TNF-238A
group had a prolonged 12-month progression-free and overall survival of
86% and 100% versus 44% and 84% (P = .003 and
P = .07) in pts with the TNF-238G allele, respectively.
These findings suggest that regulatory polymorphisms of the TNF-
gene can affect TNF- production and predict the outcome after Thal
therapy, particularly in those MM pts who are genetically defined as
"high producers" of TNF-.
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