title: A phase I trial of immunostimulatory CpG 7909 oligodeoxynucleotide and 90 yttrium ibritumomab tiuxetan radioimmunotherapy for relapsed B-cell non-Hodgkin lymphoma.
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 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.
authors.affiliation: Department of Internal Medicine, Division of Hematology, Mayo Clinic College of Medicine and Mayo Foundation, Rochester, Minnesota.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Witzig
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Wiseman
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Maurer
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Habermann
authors.forename: Ivana N M
authors.initials: IN
authors.lastname: Micallef
authors.forename: Grzegorz S
authors.initials: GS
authors.lastname: Nowakowski
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Ansell
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Colgan
authors.forename: David J
authors.initials: DJ
authors.lastname: Inwards
authors.forename: Luis F
authors.initials: LF
authors.lastname: Porrata
authors.forename: Brian K
authors.initials: BK
authors.lastname: Link
authors.forename: Clive S
authors.initials: CS
authors.lastname: Zent
authors.forename: Patrick B
authors.initials: PB
authors.lastname: Johnston
authors.forename: Tait D
authors.initials: TD
authors.lastname: Shanafelt
authors.forename: Cristine
authors.initials: C
authors.lastname: Allmer
authors.forename: Yan W
authors.initials: YW
authors.lastname: Asmann
authors.forename: Mamta
authors.initials: M
authors.lastname: Gupta
authors.forename: Zuhair K
authors.initials: ZK
authors.lastname: Ballas
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Smith
authors.forename: George J
authors.initials: GJ
authors.lastname: Weiner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000187:drug effects / Q000473:pathology; D004334:Drug Administration Schedule; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D008228:Lymphoma, Non-Hodgkin / Q000097:blood / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides / Q000627:therapeutic use*; D016499:Radioimmunotherapy; D019275:Radiopharmaceuticals / Q000627:therapeutic use*; D012008:Recurrence; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015021:Yttrium Radioisotopes
chemical_list: D000911:Antibodies, Monoclonal; C508609:IL10 protein, human; D007155:Immunologic Factors; D053583:Interleukin-1beta; D009838:Oligodeoxyribonucleotides; C483020:ProMune; D019275:Radiopharmaceuticals; D014409:Tumor Necrosis Factor-alpha; D015021:Yttrium Radioisotopes; D016753:Interleukin-10; C422802:ibritumomab tiuxetan