T-cell lymphoma - zanolimumab

Cutaneous T-cell lymphoma (CTCL) is a form of non-Hodgkin lymphoma that largely affects the skin. There are two main forms - mycosis fungoides, where the blood is unaffected, and Sezary syndrome, where abnormal T-cells are found in the blood as well as the skin and lymph glands.

One possible method of treatment is to inhibit the activation and proliferation of T-cells, and the monoclonal antibody zanolimumab is a CD4 antagonist which interacts with an epitope expressed by a subset of T-cells and on human monocytes of membrane bound CD4.¹ It was initially developed for rheumatoid arthritis and psoriasis but this was unsuccessful because of a lack of efficacy; however it has shown promise in CTCL. It was discovered by Genmab and is being developed with Medarex.

Two prospective multicentre open label uncontrolled Phase II trials have been carried out in patients who had failed at least two prior treatments; many of the late stage patients had failed four or more.² In one, 25 patients with treatment refractory and persistent early stage mucosis fungoides were given 280 or 560mg of zanolimumab as an infusion once a week; in the other, 22 patients with treatment refractory and persistent advanced stage CTCL were given weekly infusions of 280 or 980mg. They were given 17 weekly infusions in consecutive weeks, and across the two trials 13 of the 38 MF patients achieved an objective response, and a similar response was seen in two of the nine with Sezary syndrome.

A response rate of 56% was seen in the high-dose MF patients, and 15% in the low dose group. A dose dependent drop in CD4+ T-cells was seen. Two patients who had Type II diabetes experienced cytokine release syndrome, but most of the side-effects observed were minor, including dermatitis, eczema, pruritis and flu-like symptoms. Further Phase II trials are being carried out with patients being given 980mg doses.