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

作者：Witzig Thomas E^*; Wiseman Gregory A; Maurer Matthew J; Habermann Thomas M; Micallef Ivana N 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

来源：American Journal of Hematology, 2013, 88(7): 589-593.

DOI：10.1002/ajh.23460

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 TNF, and an increase in IL1, 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.

• 出版日期2013-7