TY - JOUR
T1 - Humanized anti-CD20 antibody, veltuzumab, in refractory/recurrent non-Hodgkin's lymphoma
T2 - Phase I/II results
AU - Morschhauser, Franck
AU - Leonard, John P.
AU - Fayad, Luis
AU - Coiffier, Bertrand
AU - Petillon, Marie Odile
AU - Coleman, Morton
AU - Schuster, Stephen J.
AU - Dyer, Martin J.S.
AU - Horne, Heather
AU - Teoh, Nick
AU - Wegener, William A.
AU - Goldenberg, David M.
PY - 2009/7/10
Y1 - 2009/7/10
N2 - 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.
AB - 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.
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U2 - 10.1200/JCO.2008.19.9117
DO - 10.1200/JCO.2008.19.9117
M3 - Article
C2 - 19451441
AN - SCOPUS:70249106098
SN - 0732-183X
VL - 27
SP - 3346
EP - 3353
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 20
ER -