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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.

AbstractBACKGROUND:
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.
AuthorsSven de Vos, Andres Forero-Torres, Stephen M 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
JournalJournal of hematology & oncology (J Hematol Oncol) Vol. 7 Pg. 44 (Jun 12 2014) ISSN: 1756-8722 [Electronic] England
PMID24919462 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Monoclonal, Humanized
  • CD40 Antigens
  • FCGR3A protein, human
  • Fc gamma receptor IIA
  • Receptors, IgG
  • dacetuzumab
Topics
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized (adverse effects, pharmacokinetics, therapeutic use)
  • CD40 Antigens (immunology, metabolism)
  • Chills (chemically induced)
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Fatigue (chemically induced)
  • Female
  • Headache (chemically induced)
  • Humans
  • Kaplan-Meier Estimate
  • Lymphoma, Large B-Cell, Diffuse (drug therapy, pathology)
  • Lymphopenia (chemically induced)
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Polymorphism, Single Nucleotide
  • Receptors, IgG (genetics)
  • Remission Induction
  • Treatment Outcome
  • Young Adult

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