A phase II study of dacetuzumab (SGN-40) in patients with relapsed diffuse large B-cell lymphoma (DLBCL) and correlative analyses of patient-specific factors

Sven De Vos, Andres Forero-Torres, Stephen Maxted Ansell, Brad Kahl, Bruce D. Cheson, Nancy L. Bartlett, Richard R. Furman, Jane N. Winter, Henry Kaplan, John Timmerman, Nancy C. Whiting, Jonathan G. Drachman, Ranjana Advani

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Background: Patients with DLBCL who are ineligible for or have relapsed after aggressive salvage chemotherapy have a poor prognosis. CD40 is expressed on multiple B-cell neoplasms including DLBCL and is a potential target for immunotherapy. Dacetuzumab (SGN-40), a non-blocking, partial agonist, humanized IgG1, anti-CD40 monoclonal antibody, has previously demonstrated anti-lymphoma activity in a phase I study. Methods. A phase II study was undertaken to evaluate the rate and duration of objective responses and safety of single-agent dacetuzumab in relapsed DLBCL. Forty-six adult patients with relapsed/refractory DLBCL received up to 12 cycles of intravenous dacetuzumab using intrapatient dose-escalation to a target dose of 8 mg/kg/week in an initial 5-week cycle, followed by 4-week cycles of 8 mg/kg/week. Study endpoints included rate and duration of objective responses, safety, survival, pharmacokinetics, immunogenicity, and exploratory correlative studies. Results: Overall response rate was 9% and disease control rate (complete remission + partial remission + stable disease) was 37%. Common non-hematologic adverse events (AEs) included fatigue, headache, chills, fever, and nausea. The most frequent Grade 3-4 non-hematologic AE was deep venous thrombosis (3 patients). Grade 3-4 lymphopenia (41%), neutropenia (13%), or thrombocytopenia (19%) occurred without associated infection or bleeding. Reversible ocular events, including conjunctivitis and ocular hyperemia, occurred in 8 patients (17%). Patient-specific factors, including Fc-gamma-RIIIa polymorphism, did not appear to correlate with antitumor activity. Conclusions: Single-agent dacetuzumab has modest activity and manageable toxicity in unselected patients with relapsed DLBCL. Combination regimens and robust methods of patient selection may be necessary for further development. Trial registration. ClinicalTrials.gov identifier NCT00435916.

Original languageEnglish (US)
Article number44
JournalJournal of Hematology and Oncology
Volume7
Issue number1
DOIs
StatePublished - Jun 12 2014

Fingerprint

Lymphoma, Large B-Cell, Diffuse
Safety
Chills
Lymphopenia
Conjunctivitis
Hyperemia
Neutropenia
Venous Thrombosis
Thrombocytopenia
Immunotherapy
Nausea
Patient Selection
Fatigue
Headache
dacetuzumab
Lymphoma
B-Lymphocytes
Fever
Pharmacokinetics
Immunoglobulin G

Keywords

  • CD40
  • Dacetuzumab
  • Diffuse large B-cell lymphoma
  • DLBCL

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research
  • Molecular Biology

Cite this

A phase II study of dacetuzumab (SGN-40) in patients with relapsed diffuse large B-cell lymphoma (DLBCL) and correlative analyses of patient-specific factors. / De Vos, Sven; Forero-Torres, Andres; Ansell, Stephen Maxted; Kahl, Brad; Cheson, Bruce D.; Bartlett, Nancy L.; Furman, Richard R.; Winter, Jane N.; Kaplan, Henry; Timmerman, John; Whiting, Nancy C.; Drachman, Jonathan G.; Advani, Ranjana.

In: Journal of Hematology and Oncology, Vol. 7, No. 1, 44, 12.06.2014.

Research output: Contribution to journalArticle

De Vos, S, Forero-Torres, A, Ansell, SM, Kahl, B, Cheson, BD, Bartlett, NL, Furman, RR, Winter, JN, Kaplan, H, Timmerman, J, Whiting, NC, Drachman, JG & Advani, R 2014, 'A phase II study of dacetuzumab (SGN-40) in patients with relapsed diffuse large B-cell lymphoma (DLBCL) and correlative analyses of patient-specific factors', Journal of Hematology and Oncology, vol. 7, no. 1, 44. https://doi.org/10.1186/1756-8722-7-44
De Vos, Sven ; Forero-Torres, Andres ; Ansell, Stephen Maxted ; Kahl, Brad ; Cheson, Bruce D. ; Bartlett, Nancy L. ; Furman, Richard R. ; Winter, Jane N. ; Kaplan, Henry ; Timmerman, John ; Whiting, Nancy C. ; Drachman, Jonathan G. ; Advani, Ranjana. / A phase II study of dacetuzumab (SGN-40) in patients with relapsed diffuse large B-cell lymphoma (DLBCL) and correlative analyses of patient-specific factors. In: Journal of Hematology and Oncology. 2014 ; Vol. 7, No. 1.
@article{2c18ca4dd8c541fcb788cd65c24317fb,
title = "A phase II study of dacetuzumab (SGN-40) in patients with relapsed diffuse large B-cell lymphoma (DLBCL) and correlative analyses of patient-specific factors",
abstract = "Background: Patients with DLBCL who are ineligible for or have relapsed after aggressive salvage chemotherapy have a poor prognosis. CD40 is expressed on multiple B-cell neoplasms including DLBCL and is a potential target for immunotherapy. Dacetuzumab (SGN-40), a non-blocking, partial agonist, humanized IgG1, anti-CD40 monoclonal antibody, has previously demonstrated anti-lymphoma activity in a phase I study. Methods. A phase II study was undertaken to evaluate the rate and duration of objective responses and safety of single-agent dacetuzumab in relapsed DLBCL. Forty-six adult patients with relapsed/refractory DLBCL received up to 12 cycles of intravenous dacetuzumab using intrapatient dose-escalation to a target dose of 8 mg/kg/week in an initial 5-week cycle, followed by 4-week cycles of 8 mg/kg/week. Study endpoints included rate and duration of objective responses, safety, survival, pharmacokinetics, immunogenicity, and exploratory correlative studies. Results: Overall response rate was 9{\%} and disease control rate (complete remission + partial remission + stable disease) was 37{\%}. Common non-hematologic adverse events (AEs) included fatigue, headache, chills, fever, and nausea. The most frequent Grade 3-4 non-hematologic AE was deep venous thrombosis (3 patients). Grade 3-4 lymphopenia (41{\%}), neutropenia (13{\%}), or thrombocytopenia (19{\%}) occurred without associated infection or bleeding. Reversible ocular events, including conjunctivitis and ocular hyperemia, occurred in 8 patients (17{\%}). Patient-specific factors, including Fc-gamma-RIIIa polymorphism, did not appear to correlate with antitumor activity. Conclusions: Single-agent dacetuzumab has modest activity and manageable toxicity in unselected patients with relapsed DLBCL. Combination regimens and robust methods of patient selection may be necessary for further development. Trial registration. ClinicalTrials.gov identifier NCT00435916.",
keywords = "CD40, Dacetuzumab, Diffuse large B-cell lymphoma, DLBCL",
author = "{De Vos}, Sven and Andres Forero-Torres and Ansell, {Stephen Maxted} and Brad Kahl and Cheson, {Bruce D.} and Bartlett, {Nancy L.} and Furman, {Richard R.} and Winter, {Jane N.} and Henry Kaplan and John Timmerman and Whiting, {Nancy C.} and Drachman, {Jonathan G.} and Ranjana Advani",
year = "2014",
month = "6",
day = "12",
doi = "10.1186/1756-8722-7-44",
language = "English (US)",
volume = "7",
journal = "Journal of Hematology and Oncology",
issn = "1756-8722",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - A phase II study of dacetuzumab (SGN-40) in patients with relapsed diffuse large B-cell lymphoma (DLBCL) and correlative analyses of patient-specific factors

AU - De Vos, Sven

AU - Forero-Torres, Andres

AU - Ansell, Stephen Maxted

AU - Kahl, Brad

AU - Cheson, Bruce D.

AU - Bartlett, Nancy L.

AU - Furman, Richard R.

AU - Winter, Jane N.

AU - Kaplan, Henry

AU - Timmerman, John

AU - Whiting, Nancy C.

AU - Drachman, Jonathan G.

AU - Advani, Ranjana

PY - 2014/6/12

Y1 - 2014/6/12

N2 - Background: Patients with DLBCL who are ineligible for or have relapsed after aggressive salvage chemotherapy have a poor prognosis. CD40 is expressed on multiple B-cell neoplasms including DLBCL and is a potential target for immunotherapy. Dacetuzumab (SGN-40), a non-blocking, partial agonist, humanized IgG1, anti-CD40 monoclonal antibody, has previously demonstrated anti-lymphoma activity in a phase I study. Methods. A phase II study was undertaken to evaluate the rate and duration of objective responses and safety of single-agent dacetuzumab in relapsed DLBCL. Forty-six adult patients with relapsed/refractory DLBCL received up to 12 cycles of intravenous dacetuzumab using intrapatient dose-escalation to a target dose of 8 mg/kg/week in an initial 5-week cycle, followed by 4-week cycles of 8 mg/kg/week. Study endpoints included rate and duration of objective responses, safety, survival, pharmacokinetics, immunogenicity, and exploratory correlative studies. Results: Overall response rate was 9% and disease control rate (complete remission + partial remission + stable disease) was 37%. Common non-hematologic adverse events (AEs) included fatigue, headache, chills, fever, and nausea. The most frequent Grade 3-4 non-hematologic AE was deep venous thrombosis (3 patients). Grade 3-4 lymphopenia (41%), neutropenia (13%), or thrombocytopenia (19%) occurred without associated infection or bleeding. Reversible ocular events, including conjunctivitis and ocular hyperemia, occurred in 8 patients (17%). Patient-specific factors, including Fc-gamma-RIIIa polymorphism, did not appear to correlate with antitumor activity. Conclusions: Single-agent dacetuzumab has modest activity and manageable toxicity in unselected patients with relapsed DLBCL. Combination regimens and robust methods of patient selection may be necessary for further development. Trial registration. ClinicalTrials.gov identifier NCT00435916.

AB - Background: Patients with DLBCL who are ineligible for or have relapsed after aggressive salvage chemotherapy have a poor prognosis. CD40 is expressed on multiple B-cell neoplasms including DLBCL and is a potential target for immunotherapy. Dacetuzumab (SGN-40), a non-blocking, partial agonist, humanized IgG1, anti-CD40 monoclonal antibody, has previously demonstrated anti-lymphoma activity in a phase I study. Methods. A phase II study was undertaken to evaluate the rate and duration of objective responses and safety of single-agent dacetuzumab in relapsed DLBCL. Forty-six adult patients with relapsed/refractory DLBCL received up to 12 cycles of intravenous dacetuzumab using intrapatient dose-escalation to a target dose of 8 mg/kg/week in an initial 5-week cycle, followed by 4-week cycles of 8 mg/kg/week. Study endpoints included rate and duration of objective responses, safety, survival, pharmacokinetics, immunogenicity, and exploratory correlative studies. Results: Overall response rate was 9% and disease control rate (complete remission + partial remission + stable disease) was 37%. Common non-hematologic adverse events (AEs) included fatigue, headache, chills, fever, and nausea. The most frequent Grade 3-4 non-hematologic AE was deep venous thrombosis (3 patients). Grade 3-4 lymphopenia (41%), neutropenia (13%), or thrombocytopenia (19%) occurred without associated infection or bleeding. Reversible ocular events, including conjunctivitis and ocular hyperemia, occurred in 8 patients (17%). Patient-specific factors, including Fc-gamma-RIIIa polymorphism, did not appear to correlate with antitumor activity. Conclusions: Single-agent dacetuzumab has modest activity and manageable toxicity in unselected patients with relapsed DLBCL. Combination regimens and robust methods of patient selection may be necessary for further development. Trial registration. ClinicalTrials.gov identifier NCT00435916.

KW - CD40

KW - Dacetuzumab

KW - Diffuse large B-cell lymphoma

KW - DLBCL

UR - http://www.scopus.com/inward/record.url?scp=84903272348&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84903272348&partnerID=8YFLogxK

U2 - 10.1186/1756-8722-7-44

DO - 10.1186/1756-8722-7-44

M3 - Article

VL - 7

JO - Journal of Hematology and Oncology

JF - Journal of Hematology and Oncology

SN - 1756-8722

IS - 1

M1 - 44

ER -