TY - JOUR
T1 - Pilot study of dacetuzumab in combination with rituximab and gemcitabine for relapsed or refractory diffuse large B-cell lymphoma
AU - Forero-Torres, Andres
AU - Bartlett, Nancy
AU - Beaven, Anne
AU - Myint, Han
AU - Nasta, Sunita
AU - Northfelt, Donald W.
AU - Whiting, Nancy C.
AU - Drachman, Jonathan G.
AU - Lobuglio, Albert F.
AU - Moskowitz, Craig H.
N1 - Funding Information:
The study was sponsored by Seattle Genetics, Inc. The authors and sponsor were jointly responsible for the study design. The sponsor verified the accuracy of collected data and conducted the statistical analyses. The decision to submit the manuscript for publication was jointly made by the sponsor and all the authors. The sponsor assisted in preparation of the manuscript, including assistance with the editorial/submission process.
PY - 2013/2
Y1 - 2013/2
N2 - 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/m2 IV weekly in cycle 1, then every 28 days) and gemcitabine (1000 mg/m2 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%.
AB - 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/m2 IV weekly in cycle 1, then every 28 days) and gemcitabine (1000 mg/m2 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%.
KW - Antibody-based immunotherapy
KW - Chemotherapeutic approaches
KW - Lymphoma and Hodgkin disease
UR - http://www.scopus.com/inward/record.url?scp=84872047730&partnerID=8YFLogxK
U2 - 10.3109/10428194.2012.710328
DO - 10.3109/10428194.2012.710328
M3 - Article
C2 - 22775314
AN - SCOPUS:84872047730
SN - 1042-8194
VL - 54
SP - 277
EP - 283
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 2
ER -