Pilot study of dacetuzumab in combination with rituximab and gemcitabine for relapsed or refractory diffuse large B-cell lymphoma

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/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%.

Keywords::

• Lymphoma and Hodgkin disease
• antibody-based immunotherapy
• chemotherapeutic approaches

Acknowledgements

The authors gratefully acknowledge the help of Tiffany Griffin (Seattle Genetics, Inc.) and Heather Lewis (University of Alabama at Birmingham Comprehensive Cancer Center) for assistance in preparing the manuscript, Emmanuel Mohandoss for statistical analysis, and Jon Holmlund, MD for assistance in drafting the manuscript as a paid consultant to Seattle Genetics, Inc.

Potential conflict of interest:

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