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Ansell, S.M. et al.

Ansell, Witzig, Kurtin, Sloan, Jelinek, Howell, Markovic, Habermann, Klee, Atherton, Erlichman,

Phase 1 study of interleukin-12 in combination with rituximab in patients with B-cell non-Hodgkin lymphoma.

Rituximab is a chimeric murine/human monoclonal antibody that binds to CD20 on B lymphocytes. Although binding of the Fab domain may induce apoptosis, the Fc domain recruits immune effector functions to mediate cell lysis. Interleukin-12 (IL-12) facilitates cytolytic T-cell responses, enhances the lytic activity of natural killer (NK) cells, and induces the secretion of interferon gamma (IFN-gamma) by both T and NK cells. Therefore, the hypothesis was considered that combining IL-12 with rituximab would augment the immune-mediated cell lysis induced by rituximab. A phase 1 study of IL-12 in combination with rituximab was conducted in 43 adults with B-cell lymphoma to determine the optimal immunologic dose of this combination. Rituximab was administered at a dose of 375 mg/m(2) by intravenous infusion weekly for 4 weeks, and IL-12 was given subcutaneously twice weekly. The starting dose of IL-12 was 30 ng/kg and this was escalated to 500 ng/kg. Constitutional symptoms and liver enzyme elevations at 500 ng/kg of IL-12 were dose limiting. A greater than 20-fold increase in the serum levels of IFN-gamma and a 2.5- to 5-fold increase in inducible protein 10 ( IP-10) levels was seen at IL-12 doses of 100 ng/kg or greater. Objective responses occurred in 29 of the 43 patients (69%), with 8 of 11 complete responses seen at IL-12 doses of 300 ng/kg or greater. The optimal immunologic dose of IL-12 in combination with rituximab was determined to be 300 ng/kg subcutaneously twice weekly starting on day 2. These data suggest that IL-12 and rituximab is an active combination and further studies of this combination in B-cell non-Hodgkin lymphoma are warranted.[1]

References

Phase 1 study of interleukin-12 in combination with rituximab in patients with B-cell non-Hodgkin lymphoma. Ansell, S.M., Witzig, T.E., Kurtin, P.J., Sloan, J.A., Jelinek, D.F., Howell, K.G., Markovic, S.N., Habermann, T.M., Klee, G.G., Atherton, P.J., Erlichman, C. Blood (2002) [Pubmed]

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