Anti-CD20 and CD22 Therapy Is Effective in Non-Hodgkin Lymphoma

Rituximab is a monoclonal antibody approved for treatment of non-Hodgkin lymphomas that targets CD20, an antigen expressed by mature B cells. Single-agent rituximab treatment elicits clinical responses in many patients with non-Hodgkin lymphomas such as follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL), but few treatment options are available for patients who relapse or are refractory to rituximab. Another B-cell antigen, CD22, which is expressed by the vast majority of B-cell cancers but not by lymphocyte precursors or memory B cells, also represents an attractive target for non-Hodgkin lymphoma therapy. Inotuzumab ozogamicin (INO) is a CD22-targeted therapy in which a humanized CD22 antibody is conjugated to calicheamicin, a cytotoxic antibiotic. In a multicenter open-label phase I/II study, Fayad and colleagues evaluated the combination of rituximab and inotuzumab ozogamicin (R-INO) in patients with relapsed FL, relapsed DLBCL, or refractory non-Hodgkin lymphomas. A dose-escalation study was first performed to determine the maximum tolerated dose followed by analysis of an expanded cohort to determine safety and efficacy. R-INO treatment led to sharp decreases in CD19⁺ B-cell counts and CD22 expression and overall response rates of 87%, 74%, and 20% in relapsed FL, relapsed DLBCL, and refractory non-Hodgkin lymphomas, respectively, including complete responses in 62% of FL patients and 50% of DLBCL patients. Responses were durable, and the median overall survival had not yet been reached in patients with relapsed FL or DLBCL after over 2 years. Common adverse events were generally reversible and included thrombocytopenia, neutropenia, and altered liver function. Although direct comparison with previous single-agent studies is difficult due to patient population differences, the activity of R-INO in relapsed and refractory disease suggests that further evaluation of this combination approach is warranted in CD20⁺/CD22⁺ B-cell non-Hodgkin lymphoma.

Fayad L, Offner F, Smith MR, Verhoef G, Johnson P, Kaufman JL, et al. 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. J Clin Oncol 2013 Jan 7 [Epub ahead of print].