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

Research output: Contribution to journalArticle

17 Citations (Scopus)

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

Fingerprint

Radioimmunotherapy
Oligodeoxyribonucleotides
B-Cell Lymphoma
Non-Hodgkin's Lymphoma
B-Lymphocytes
Oligonucleotides
Interleukin-10
Disease-Free Survival
Radiation
Phenotype
Biopsy
ibritumomab tiuxetan
ProMune

ASJC Scopus subject areas

  • Hematology

Cite this

A phase I trial of immunostimulatory CpG 7909 oligodeoxynucleotide and 90yttrium ibritumomab tiuxetan radioimmunotherapy for relapsed B-cell non-Hodgkin lymphoma. / Witzig, Thomas Elmer; Wiseman, Gregory A.; Maurer, Matthew J.; Habermann, Thomas Matthew; Micallef, Ivana; Nowakowski, Grzegorz S; Ansell, Stephen Maxted; Colgan, Joseph P.; Inwards, David J.; Porrata, Luis F.; Link, Brian K.; Zent, Clive S.; Johnston, Patrick Bruce; Shanafelt, Tait D.; Allmer, Cristine; Asmann, Yan; Gupta, Mamta; Ballas, Zuhair K.; Smith, Brian J.; Weiner, George J.

In: American Journal of Hematology, Vol. 88, No. 7, 07.2013, p. 589-593.

Research output: Contribution to journalArticle

Witzig, Thomas Elmer ; Wiseman, Gregory A. ; Maurer, Matthew J. ; Habermann, Thomas Matthew ; Micallef, Ivana ; Nowakowski, Grzegorz S ; Ansell, Stephen Maxted ; Colgan, Joseph P. ; Inwards, David J. ; Porrata, Luis F. ; Link, Brian K. ; Zent, Clive S. ; Johnston, Patrick Bruce ; Shanafelt, Tait D. ; Allmer, Cristine ; Asmann, Yan ; Gupta, Mamta ; Ballas, Zuhair K. ; Smith, Brian J. ; Weiner, George J. / A phase I trial of immunostimulatory CpG 7909 oligodeoxynucleotide and 90yttrium ibritumomab tiuxetan radioimmunotherapy for relapsed B-cell non-Hodgkin lymphoma. In: American Journal of Hematology. 2013 ; Vol. 88, No. 7. pp. 589-593.
@article{e2d7e1c0d0f342479cdb7928fedb2f2f,
title = "A phase I trial of immunostimulatory CpG 7909 oligodeoxynucleotide and 90yttrium 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/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.",
author = "Witzig, {Thomas Elmer} and Wiseman, {Gregory A.} and Maurer, {Matthew J.} and Habermann, {Thomas Matthew} and Ivana Micallef and Nowakowski, {Grzegorz S} and Ansell, {Stephen Maxted} and Colgan, {Joseph P.} and Inwards, {David J.} and Porrata, {Luis F.} and Link, {Brian K.} and Zent, {Clive S.} and Johnston, {Patrick Bruce} and Shanafelt, {Tait D.} and Cristine Allmer and Yan Asmann and Mamta Gupta and Ballas, {Zuhair K.} and Smith, {Brian J.} and Weiner, {George J.}",
year = "2013",
month = "7",
doi = "10.1002/ajh.23460",
language = "English (US)",
volume = "88",
pages = "589--593",
journal = "American Journal of Hematology",
issn = "0361-8609",
publisher = "Wiley-Liss Inc.",
number = "7",

}

TY - JOUR

T1 - A phase I trial of immunostimulatory CpG 7909 oligodeoxynucleotide and 90yttrium ibritumomab tiuxetan radioimmunotherapy for relapsed B-cell non-Hodgkin lymphoma

AU - Witzig, Thomas Elmer

AU - Wiseman, Gregory A.

AU - Maurer, Matthew J.

AU - Habermann, Thomas Matthew

AU - Micallef, Ivana

AU - Nowakowski, Grzegorz S

AU - Ansell, Stephen Maxted

AU - Colgan, Joseph P.

AU - Inwards, David J.

AU - Porrata, Luis F.

AU - Link, Brian K.

AU - Zent, Clive S.

AU - Johnston, Patrick Bruce

AU - Shanafelt, Tait D.

AU - Allmer, Cristine

AU - Asmann, Yan

AU - Gupta, Mamta

AU - Ballas, Zuhair K.

AU - Smith, Brian J.

AU - Weiner, George J.

PY - 2013/7

Y1 - 2013/7

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84879416242&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84879416242&partnerID=8YFLogxK

U2 - 10.1002/ajh.23460

DO - 10.1002/ajh.23460

M3 - Article

C2 - 23619698

AN - SCOPUS:84879416242

VL - 88

SP - 589

EP - 593

JO - American Journal of Hematology

JF - American Journal of Hematology

SN - 0361-8609

IS - 7

ER -