Fanale, Michelle, Assouline, Sarit, Kuruvilla, John, Solal-Celigny, Philippe, Heo, Dae S., Verhoef, Gregor, Corradini, Paolo ORCID: 0000-0002-9186-1353, Abramson, Jeremy S., Offner, Fritz, Engert, Andreas, Dyer, Martin J. S., Carreon, Daniel, Ewald, Brett, Baeck, Johan, Younes, Anas and Freedman, Arnold S. (2014). Phase IA/II, multicentre, open-label study of the CD40 antagonistic monoclonal antibody lucatumumab in adult patients with advanced non-Hodgkin or Hodgkin lymphoma. Br. J. Haematol., 164 (2). S. 258 - 266. HOBOKEN: WILEY. ISSN 1365-2141

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Abstract

Despite advancements in the treatment of non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL), patients continue to relapse and thus a need for new targeted therapies remains. The CD40 receptor is highly expressed on neoplastic B cells and activation leads to enhanced proliferation and survival. Lucatumumab (HCD122) is a fully human antagonistic CD40 monoclonal antibody. A phase IA/II study was designed to determine the maximum tolerated dose (MTD) and activity of lucatumumab in patients with relapsed/refractory lymphoma. Determination of the MTD was the primary objective of the phase IA dose escalation portion and clinical response was the primary objective of the phase II dose expansion portion. Patients received escalating doses of lucatumumab administered intravenously once weekly for 4 weeks of an 8-week cycle. MTD was determined at 4mg/kg of lucatumumab. A total of 111 patients with NHL (n=74) and HL (n=37) were enrolled. Responses were observed across various lymphoma subtypes. The overall response rate by computed tomography among patients with follicular lymphoma (FL) and marginal zone lymphoma of mucosa-associated lymphatic tissue (MZL/MALT) was 33.3% and 42.9%, respectively. Lucatumumab demonstrates modest activity in relapsed/refractory patients with advanced lymphoma, suggesting that targeting of CD40 warrants further investigation.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Fanale, MichelleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Assouline, SaritUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kuruvilla, JohnUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Solal-Celigny, PhilippeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heo, Dae S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Verhoef, GregorUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Corradini, PaoloUNSPECIFIEDorcid.org/0000-0002-9186-1353UNSPECIFIED
Abramson, Jeremy S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Offner, FritzUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Engert, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dyer, Martin J. S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Carreon, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ewald, BrettUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baeck, JohanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Younes, AnasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Freedman, Arnold S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-451817
DOI: 10.1111/bjh.12630
Journal or Publication Title: Br. J. Haematol.
Volume: 164
Number: 2
Page Range: S. 258 - 266
Date: 2014
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1365-2141
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
REED-STERNBERG CELLS; ANTIGEN-EXPRESSION; ANTI-CD40; DACETUZUMAB; RITUXIMAB; LEUKEMIA; EFFICACY; CRITERIA; TRIALS; HCD122Multiple languages
HematologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/45181

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