Originally published as JCO Early Release 10.1200/JCO.2008.19.9117 on May 18 2009

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Humanized Anti-CD20 Antibody, Veltuzumab, in Refractory/Recurrent Non-Hodgkin's Lymphoma: Phase I/II Results

From the Service des Maladies du Sang Centre Hospitalier Regional, Lille; Centre Hospitalier Lyon-Sud, Lyon, France; New York Presbyterian Hospital, Weill Cornell Medical College, New York, NY; The University of Texas M. D. Anderson Cancer Center, Houston, TX; Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA; Medical Research Council Toxicology Unit, Leicester University, Leicester, United Kingdom; Immunomedics, Inc, Morris Plains; and Garden State Cancer Center, Belleville, NJ.

Corresponding author: Franck Morschhauser, MD, Lille University Hospital, Service des Maladies du Sang, Rue Michel Polonovski, 59037 Lille, France; e-mail: f-morschhauser{at}chru-lille.fr, fmorschhauser{at}gmail.com.

Purpose This is a multicenter phase I/II dose-finding study in relapsed/refractory B-cell non-Hodgkin's lymphoma (NHL) evaluating veltuzumab, a humanized anti-CD20 antibody with structure-function differences from chimeric rituximab.

Patients and Methods Eighty-two patients (median age, 64 years; 79% stage III/IV, one to nine prior treatments) received four once-weekly doses of 80 to 750 mg/m² of veltuzumab and were assessed for safety, efficacy, pharmacodynamics, pharmacokinetics, and immunogenicity.

Results Veltuzumab was well tolerated, with no grade 3 to 4 drug-related adverse events despite short infusion times (typically 2 hours initially, 1 hour subsequently at doses < 375 mg/m²). In follicular lymphoma, 24 (44%) of 55 patients had objective responses (OR), with 15 (27%) complete responses (CRs) or CRs unconfirmed (CRus) by International Working Group criteria, and with some responses occurring despite two to five prior rituximab-containing regimens, less favorable prognosis (elevated lactate dehydrogenase, tumors > 5 cm, and Follicular Lymphoma International Prognostic Index 2), and at all dose levels. The CRs/CRus were durable (median duration, 19.7 months), with five patients still ongoing (15.9 to 37.6 months duration). In marginal zone lymphoma, five (83%) of six patients had ORs, with two CRs/CRus (33%), and in diffuse large B-cell lymphoma, three (43%) of seven patients achieved partial responses. At all dose levels studied, B cells were depleted after the first infusion, veltuzumab serum half-lives were similar after the fourth infusion, and mean antibody serum levels exceeded values considered important for anti-CD20 therapy (ie, 25 µg/mL).

Conclusion Veltuzumab appeared safe and active at all tested doses, encouraging further study, including dose levels less than those typically used with rituximab.

Presented in part at the 43rd Annual Meeting of the American Society of Clinical Oncology, June 1-5, 2007, Chicago, IL.

ClinicalTrials.gov registry: NCT00285428 (US), NCT00596804 (Europe).

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical Trials repository link available on JCO.org.

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