Polymorphisms of the tumor necrosis factor-α gene promoter predict for outcome after thalidomide therapy in relapsed and refractory multiple myeloma

• Verfasst von: Neben, Kai [VerfasserIn]
• Verfasst von: Mytilineos, Joannis [VerfasserIn]
• Verfasst von: Möhler, Thomas [VerfasserIn]
• Verfasst von: Preiss, Astrid [VerfasserIn]
• Verfasst von: Krämer, Alwin [VerfasserIn]
• Verfasst von: Ho, Anthony Dick [VerfasserIn]
• Verfasst von: Opelz, Gerhard [VerfasserIn]
• Verfasst von: Goldschmidt, Hartmut [VerfasserIn]
• Titel: Polymorphisms of the tumor necrosis factor-α gene promoter predict for outcome after thalidomide therapy in relapsed and refractory multiple myeloma
• Verf.angabe: Kai Neben, Joannis Mytilineos, Thomas M. Moehler, Astrid Preiss, Alwin Kraemer, Anthony D. Ho, Gerhard Opelz, and Hartmut Goldschmidt
• E-Jahr: 2002
• Jahr: [15 September 2002]
• Umfang: 3 S.
• Illustrationen: Diagramme
• Fussnoten: Gesehen am 10.12.2021
• Titel Quelle: Enthalten in: Blood
• Ort Quelle: Washington, DC : American Society of Hematology, 1946
• Jahr Quelle: 2002
• Band/Heft Quelle: 100(2002), 6, Seite 2263-2265
• ISSN Quelle: 1528-0020
• DOI: doi:10.1182/blood.V100.6.2263
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1780935943

Abstract

Thalidomide (Thal) is a drug with antiangiogenic, anti-inflammatory, and immunomodulatory properties that was found to inhibit the production of tumor necrosis factor-α (TNF-α) in vitro. We studied single nucleotide polymorphisms at positions −308 and −238 of the TNF-α gene promoter and measured the corresponding TNF-α 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-α 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 andP = .07) in pts with the TNF-238G allele, respectively. These findings suggest that regulatory polymorphisms of the TNF-α gene can affect TNF-α production and predict the outcome after Thal therapy, particularly in those MM pts who are genetically defined as “high producers” of TNF-α.