Phase III randomised study of dexamethasone with or without oblimersen sodium for patients with advanced multiple myeloma

• Published in: Leukemia & lymphoma Vol. 50; no. 4; pp. 559 - 565
• Main Authors: Chanan-Khan, Asher A., Niesvizky, Ruben, Hohl, Raymond J., Zimmerman, Todd M., Christiansen, Neal P., Schiller, Gary J., Callander, Natalie, Lister, John, Oken, Martin, Jagannath, Sundar
• Format: Journal Article
• Language: English
• Published: United States Informa UK Ltd 01.01.2009; Taylor & Francis
• Subjects: Antineoplastic Agents, Hormonal - administration & dosage; Antineoplastic Agents, Hormonal - adverse effects; Antineoplastic Agents, Hormonal - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bcl-2 antisense; Dexamethasone - administration & dosage; Dexamethasone - adverse effects; Dexamethasone - therapeutic use; Drug Administration Schedule; Fatigue - chemically induced; Female; Fever - chemically induced; G3139; Genasense; Humans; Male; Middle Aged; Multiple myeloma; Multiple Myeloma - drug therapy; Multiple Myeloma - pathology; Nausea - chemically induced; oblimersen; Oligonucleotides, Antisense - administration & dosage; Thionucleotides - administration & dosage; Treatment Outcome
• ISSN: 1042-8194; 1029-2403
• DOI: 10.1080/10428190902748971

Upregulation of the Bcl-2 antiapoptotic protein is reported to be associated with aggressive clinical course in multiple myeloma. Oblimersen sodium is a bcl-2 antisense oligonucleotide complementary to the first six codons of the open-reading frame of bcl-2 mRNA that can decrease transcription of Bcl-2 protein and increase myeloma cell susceptibility to cytotoxic agents. In this phase III randomised trial, we investigated in patients with relapsed refractory myeloma whether addition of oblimersen to dexamethasone improved clinical outcomes vs. dexamethasone alone. Two hundred and twenty-four patients were randomised to receive either oblimersen dexamethasone (N = 110) or dexamethasone alone (N = 114). The primary endpoint was time to tumor progression (TTP). Final results of this study demonstrated no significant differences between the two groups in TTP or objective response rate. The oblimersen dexamethasone regimen was generally well tolerated with fatigue, fever and nausea, the most common adverse events reported.