Title: Safety and Clinical Activity of a Combination Therapy Comprising Two Antibody-Based Targeting Agents for the Treatment of Non-Hodgkin Lymphoma: Results of a Phase I/II Study Evaluating the Immunoconjugate Inotuzumab Ozogamicin With Rituximab
Authors: Fayad, Luis ×
Offner, Fritz
Smith, Mitchell R
Verhoef, Gregor
Johnson, Peter
Kaufman, Jonathan L
Rohatiner, Ama
Advani, Anjali
Foran, James
Hess, Georg
Coiffier, Bertrand
Czuczman, Myron
Gine, Eva
Durrant, Simon
Kneissl, Michelle
Luu, Kenneth T
Hua, Steven Y
Boni, Joseph
Vandendries, Erik
Dang, Nam H #
Issue Date: Feb-2013
Publisher: Grune & Stratton
Series Title: Journal of Clinical Oncology vol:31 issue:5 pages:573-583
Abstract: PURPOSEInotuzumab ozogamicin (INO) is an antibody-targeted chemotherapy agent composed of a humanized anti-CD22 antibody conjugated to calicheamicin, a potent cytotoxic agent. We performed a phase I/II study to determine the maximum-tolerated dose (MTD), safety, efficacy, and pharmacokinetics of INO plus rituximab (R-INO) for treatment of relapsed/refractory CD20(+)/CD22(+) B-cell non-Hodgkin lymphoma (NHL). PATIENTS AND METHODSA dose-escalation phase to determine the MTD of R-INO was followed by an expanded cohort to further evaluate the efficacy and safety at the MTD. Patients with relapsed follicular lymphoma (FL), relapsed diffuse large B-cell lymphoma (DLBCL), or refractory aggressive NHL received R-INO every 4 weeks for up to eight cycles.ResultsIn all, 118 patients received one or more cycles of R-INO (median, four cycles). Most common grade 3 to 4 adverse events were thrombocytopenia (31%) and neutropenia (22%). Common low-grade toxicities included hyperbilirubinemia (25%) and increased AST (36%). The MTD of INO in combination with rituximab (375 mg/m(2)) was confirmed to be the same as that for single-agent INO (1.8 mg/m(2)). Treatment at the MTD yielded objective response rates of 87%, 74%, and 20% for relapsed FL (n = 39), relapsed DLBCL (n = 42), and refractory aggressive NHL (n = 30), respectively. The 2-year progression-free survival (PFS) rate was 68% (median, not reached) for FL and 42% (median, 17.1 months) for relapsed DLBCL. CONCLUSIONR-INO demonstrated high response rates and long PFS in patients with relapsed FL or DLBCL. This and the manageable toxicity profile suggest that R-INO may be a promising option for CD20(+)/CD22(+) B-cell NHL.
ISSN: 0732-183X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Cell and Gene Therapy Applications (-)
× corresponding author
# (joint) last author

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