Inotuzumab ozogamicin as novel therapy in lymphomas

Importance of the field: More than 65,000 cases of non-Hodgkin's lymphoma are estimated to have been diagnosed in 2009; the majority are of B-cell lineage, and diffuse large cell lymphoma and follicular together account for nearly half of cases. Despite advances in treatment, most patients are not cured. Areas covered in this review: The antigen CD22 is a transmembrane glycoprotein found on mature B-cells, and on up to 90% of B-cell malignancies. Inotuzumab ozogamicin (CMC-544) is a humanized anti-CD22 monoclonal antibody conjugated with calicheamicin. Preclinical data indicate activity against B-cell tumors, and early results from clinical trials indicate activity against B-cell lymphomas including follicular lymphoma and diffuse large cell lymphoma. This paper reviews the design, pharmacokinetic and pharmacodynamic characteristics, and preclinical and clinical experience of this promising novel targeted therapy, with data derived from abstracts and published reports from 2002 to the present. What the reader will gain: This review will serve as an introduction to and overview of inotuzumab ozogamicin, and describe the rationale guiding advances in development. Take home message: The data thus far confirm the tolerability and clinical activity of inotuzumab ozogamicin in B-cell malignancies, and further investigation as a single agent as well as in combination therapy is warranted.