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A phase I trial of immunostimulatory CpG 7909 oligodeoxynucleotide and 90 yttrium ibritumomab tiuxetan radioimmunotherapy for relapsed B‐cell non‐Hodgkin lymphoma
Author(s) -
Witzig Thomas E.,
Wiseman Gregory A.,
Maurer Matthew J.,
Habermann Thomas M.,
Micallef Iva.M.,
Nowakowski Grzegorz S.,
Ansell Stephen M.,
Colgan Joseph P.,
Inwards David J.,
Porrata Luis F.,
Link Brian K.,
Zent Clive S.,
Johnston Patrick B.,
Shanafelt Tait D.,
Allmer Cristine,
Asmann Yan W.,
Gupta Mamta,
Ballas Zuhair K.,
Smith Brian J.,
Weiner George J.
Publication year - 2013
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.23460
Subject(s) - medicine , radioimmunotherapy , ibritumomab tiuxetan , gastroenterology , rituximab , oncology , lymphoma , nuclear medicine , immunology , monoclonal antibody , antibody
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 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. Am. J. Hematol. 88:589–593, 2013. © 2013 Wiley Periodicals, Inc.