Treatment of cutaneous T cell lymphoma
Dr Madeleine Duvic - Anderson Cancer Center, Houston, USA
I’m talking about a defucosylated antibody to CCR4 called mogamulizumab. It has been tested in a phase I/II trial and shown there’s no maximum tolerated dose so patients were dosed at 1mg/kg and there was a good response rate of 37% overall, higher in Sézary’s, lower in patients which was enough to justify a randomised phase III trial that’s still going on.
Are you working within any specific patient subgroups?
It seems that the Sézary patients respond very well to it, it gets rid of their circulating tumour cells in the blood with only one or two infusions. It’s capable of giving long term remissions that are durable and complete.
Are you working specifically within skin cancer?
Because it takes out T regulatory cells it has a generalised potential activity in removing T regulatory cells that would suppress reactions to any kind of cancer. It has also been approved for Japanese HTLV1 induced T-cell lymphoma so it works there and it has potential for other kinds of cancer as well through removal of T regulatory cells.
CCR4 receptor is a transmembrane receptor on the cell surface and it binds to TARC which is on endothelial cells so it’s really important in cell trafficking, getting out of the blood vessels and into the skin. The antibody works through ADCC which is enhanced by removing the fucosylated group on the antibody so it’s a new kind of antibody, a genetically engineered antibody that this is the first test of that concept of removing the fucosylated group there.
Has anything caught your eye at the conference?
I think that the melanoma story is compelling, there are so many targeted therapies and immunotherapies and I just hope some of the other cancers like CTCL will benefit from this explosion of checkpoint inhibitors and targeted trials.
Are there any upcoming studies that will draw more attention to CTCL?
There are several studies in progress, there’s a cure antibody that looks active. There are some new inhibitors of microRNA that are being tested so this is really an exciting time for CTCL research but we still don’t have the magic bullet that cures people so we have a lot of work still left to do.