Abstract |
Dacetuzumab, a CD40-targeted, humanized antibody, mediates antitumor activity through effector cell functions and direct apoptotic signal transduction. Preclinical studies demonstrated synergistic activity between dacetuzumab, gemcitabine and rituximab against non-Hodgkin lymphoma in vivo. A phase 1b safety/efficacy study of dacetuzumab in combination with rituximab and gemcitabine was conducted in relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Patients received dacetuzumab at doses of 8 or 12 mg/kg IV weekly with rituximab (375 mg/m(2) IV weekly in cycle 1, then every 28 days) and gemcitabine (1000 mg/m(2) IV, days 1, 8 and 15, or days 1 and 15). Thirty-three patients with a median age of 67 years were enrolled. Common adverse events (≥ 15%) were grade 1/2 cytokine release syndrome, nausea, fatigue, thrombocytopenia, headache, decreased appetite, dyspnea, neutropenia, pyrexia, anemia, diarrhea, edema, constipation and cough. Dacetuzumab-related grade 3/4 adverse events occurred infrequently. Six of 30 evaluable patients achieved a complete response (CR) and eight a partial response (PR) per investigator assessment for an overall response rate (ORR) of 47%.
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Authors | Andres Forero-Torres, Nancy Bartlett, Anne Beaven, Han Myint, Sunita Nasta, Donald W Northfelt, Nancy C Whiting, Jonathan G Drachman, Albert F Lobuglio, Craig H Moskowitz |
Journal | Leukemia & lymphoma
(Leuk Lymphoma)
Vol. 54
Issue 2
Pg. 277-83
(Feb 2013)
ISSN: 1029-2403 [Electronic] United States |
PMID | 22775314
(Publication Type: Journal Article)
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Chemical References |
- Antibodies, Monoclonal, Humanized
- Antibodies, Monoclonal, Murine-Derived
- Deoxycytidine
- Rituximab
- dacetuzumab
- Gemcitabine
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Antibodies, Monoclonal, Humanized
(administration & dosage, adverse effects)
- Antibodies, Monoclonal, Murine-Derived
(administration & dosage)
- Antineoplastic Combined Chemotherapy Protocols
(adverse effects, therapeutic use)
- Deoxycytidine
(administration & dosage, analogs & derivatives)
- Female
- Humans
- Lymphoma, Large B-Cell, Diffuse
(drug therapy, mortality)
- Male
- Middle Aged
- Pilot Projects
- Recurrence
- Rituximab
- Treatment Outcome
- Gemcitabine
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