Chemotherapy Foundation Symposium XXV

Update on Galiximab Combined with Rituximab (Rituxan) for Lymphoma

Presenter: Myron S. Cruczman, Roswell Park Institute, Buffalo, N.Y. CD80 is a membrane-bound, glycoprotein costimulatory molecule and a member of the B7 ligand family (B7.1). It is known for its role in regulating T-cell activity. Several studies suggest that it is involved in regulating normal and malignant cells. CD80 is temporarily exposed on the surface of activated B-cells, antigen-presenting cells, and T cells, but it is constantly expressed in various non-Hodgkin’s lymphomas (NHLs), such as follicular lymphoma, and in Hodgkin’s lym-phoma.

Galiximab (Biogen Idec) is a chimeric anti-CD80 monoclonal antibody with low immunogenicity. Cross-linking CD80 with anti-CD80 on lymphoma cells in vitro induces antibody-dependent cellular toxicity, up-regulates pro-apoptotic molecules, and inhibits cell proliferation. canadian antibiotics

A phase 1-2 study of galiximab in combination with rituximab (Rituxan, Genentech), was conducted. Rituximab is a chimeric anti-CD20 monoclonal antibody used to treat relapsed or refractory follicular lymphoma. The overall response rate for patients receiving galiximab 500 mg/m2 was 66%: 19% of patients had a complete response, 14% had an unconfirmed complete response, and 33% had a partial response. The median progression-free survival time was 12.1 months.

Patients in lower-risk groups, based on the Follicular Lym-phoma International Prognostic Index, and patients with no previous exposure to rituximab tended to have better clinical outcomes, as measured by overall response rates and progression-free survival.

Thus, galiximab/rituximab was considered safe and effective, with the possibility of prolonging event-free survival. Rit-uxi mab-naive patients may also have better outcomes with this combination.

The author is President of Pharmaceutical and Scientific Services at MarvinMGoldenberg, LLC, in Westfield, N.J.

On the basis of these findings, an “up-front” Cancer and Leukemia Group B (CALGB) phase 2 trial of prolonged dosing of eight doses of combination galiximab plus rituximab was initiated. The trial was recently closed after reaching full patient accrual. (An “up-front” trial has identified agents worthy of inclusion in multiagent trials for standard-risk patients.) Rituximab/galiximab therapy for 62 patients consisted of four weekly (induction) phases, followed by every-other-month treatment for four months (extended induction). Clinical results will be presented at a later conference.
Current or proposed galiximab trials include an international phase 3, randomized, double-blind study comparing rituximab/placebo with rituximab/galiximab in relapsed or refractory follicular lymphoma; a CALGB phase 2 monotherapy study of relapsed Hodgkin’s lymphoma; and an in vivo pilot study of low-risk patients with follicular lymphoma. Researchers are hoping to gain further insight into the mechanism of action of this exciting novel monoclonal antibody, including its direct antitumor and immunomodulatory effects.