Journal article
A Phase I Trial of Immunostimulatory CpG 7909 Oligodeoxynucleotide and 90Yttrium Ibritumomab Tiuxetan Radioimmunotherapy for Relapsed B-cell Non-Hodgkin Lymphoma
American journal of hematology, Vol.88(7), pp.589-593
07/2013
DOI: 10.1002/ajh.23460
PMCID: PMC3951424
PMID: 23619698
Abstract
Radioimmunotherapy (RIT) for relapsed indolent non-Hodgkin lymphoma produces overall response rates (ORR) of 80% with mostly partial remissions. Synthetic CpG oligonucleotides change the phenotype of malignant B-cells, are immunostimulatory, and can produce responses when injected intratumorally and combined with conventional radiation. In this phase I trial we tested systemic administration of both CpG and RIT. Eligible patients had biopsy-proven previously treated CD20+ B-cell NHL and met criteria for RIT. Patients received rituximab 250 mg/m
2
days 1,8, and 15;
111
In-ibritumomab tiuxetan days 1, 8; CpG 7909 days 6, 13, 20, 27; and 0.4 mCi/kg of
90
Y-ibritumomab tiuxetan day 15. The doses of CpG 7909 tested were 0.08, 0.16, 0.32 (six patients each) and 0.48 mg/kg (12 patients) IV over 2 hours without dose limiting toxicity. The ORR was 93% (28/30) with 63% (19/30) complete remission (CR); median progression free survival of 42.7 months (95% CI 18-NR); and median duration of response (DR) of 35 months (4.6-76+). Correlative studies demonstrated a decrease in IL10 and TNFα, and an increase in IL1β, in response to therapy. CpG 7909 at a dose of 0.48 mg/kg is safe with standard RIT and produces a high CR rate and long DR; these results warrant confirmation.
Details
- Title: Subtitle
- A Phase I Trial of Immunostimulatory CpG 7909 Oligodeoxynucleotide and 90Yttrium Ibritumomab Tiuxetan Radioimmunotherapy for Relapsed B-cell Non-Hodgkin Lymphoma
- Creators
- Thomas E Witzig - Department of Internal Medicine and the Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IowaGregory A Wiseman - Department of Internal Medicine and the Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IowaMatthew J Maurer - Department of Internal Medicine and the Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IowaThomas M Habermann - Department of Internal Medicine and the Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IowaIvana N. M Micallef - Department of Internal Medicine and the Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IowaGrzegorz S Nowakowski - Department of Internal Medicine and the Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IowaStephen M Ansell - Department of Internal Medicine and the Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IowaJoseph P Colgan - Department of Internal Medicine and the Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IowaDavid J Inwards - Department of Internal Medicine and the Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IowaLuis F Porrata - Department of Internal Medicine and the Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IowaBrian K Link - Department of Internal Medicine and the Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IowaClive S Zent - Department of Internal Medicine and the Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IowaPatrick B Johnston - Department of Internal Medicine and the Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IowaTait D Shanafelt - Department of Internal Medicine and the Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IowaCristine Allmer - Department of Internal Medicine and the Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IowaYan W Asmann - Department of Internal Medicine and the Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IowaMamta Gupta - Department of Internal Medicine and the Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IowaZuhair K Ballas - Department of Internal Medicine and the Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IowaBrian J Smith - Department of Internal Medicine and the Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IowaGeorge J Weiner - Department of Internal Medicine and the Holden Comprehensive Cancer Center, University of Iowa, Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- American journal of hematology, Vol.88(7), pp.589-593
- DOI
- 10.1002/ajh.23460
- PMID
- 23619698
- PMCID
- PMC3951424
- ISSN
- 0361-8609
- eISSN
- 1096-8652
- Language
- English
- Date published
- 07/2013
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Biostatistics; Holden Comprehensive Cancer Center; Internal Medicine
- Record Identifier
- 9983997369102771
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