A phase I trial of immunostimulatory CpG 7909 oligodeoxynucleotide and 90yttrium ibritumomab tiuxetan radioimmunotherapy for relapsed B-cell non-Hodgkin lymphoma

Thomas Elmer Witzig, Gregory A. Wiseman, Matthew J. Maurer, Thomas Matthew Habermann, Ivana Micallef, Grzegorz S Nowakowski, Stephen Maxted Ansell, Joseph P. Colgan, David J. Inwards, Luis F. Porrata, Brian K. Link, Clive S. Zent, Patrick Bruce Johnston, Tait D. Shanafelt, Cristine Allmer, Yan Asmann, Mamta Gupta, Zuhair K. Ballas, Brian J. Smith, George J. Weiner

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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/m2 days 1,8, and 15; 111In-ibritumomab tiuxetan days 1, 8; CpG 7909 days 6, 13, 20, 27; and 0.4 mCi/kg of 90Y-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 hr 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.

Original languageEnglish (US)
Pages (from-to)589-593
Number of pages5
JournalAmerican Journal of Hematology
Volume88
Issue number7
DOIs
StatePublished - Jul 2013

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ASJC Scopus subject areas

  • Hematology

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