Friday, December 13, 2013

Rituxan + Pidilizumab for Follicular Lymphoma

I think most of the main ASH announcements are over now. We'll have to wait for the post-ASH commentary that will likely come over the next few weeks. (I imagine Patient Power, for example, will have a wrap-up video sometime soon.)

But does that mean the Follicular Lymphoma news is over for now? Absolutely not. In the latest issue of The Lancet Oncology is a report on a phase 2 study of Rituxan and Pidilizumab that shows some promise -- good activity against Follicular Lymphoma cells, with side effects that aren't too horrific.

I'll be honest -- I don't know a whole lot about Pidilizumab. From what I can tell, Pidilizumab has been studied as a treatment for solid tumors as well as lymphomas. A phase 2 study of DLBCL patients after auto stem cell transplant was pretty successful. I believe that this is the first phase 2 on Follicular Lymphoma patients.

Pidilizumab seems pretty cool. It is, like Rituxan, a Monoclonal Antibody (which is why it has that -mab ending on the name). Just as Rituxan targets the protein CD20 on B cells, Pidilizumab targets something called PD-1, which stands for Programmed Cell Death 1. PD-1 does a job we don't want it to do: it blocks T cells from killing off the cell. So when a cell has PD-1 on its surface, it signals to T-cells that it should be left alone.

So guess what kind of cells has PD-1 on it? Yeah. Follicular Lymphoma. Grr. The FL cells have other substances within them that trigger PD-1 to block the T cells.

But Pidilizumab seems to do the job. It targets PD-1 and blocks it, thus allowing T cells to come and do their job. (It "unleashes" the T cells, as the article puts it, which sounds much cooler.)

So how successful is Pidilizumab, when combined with our old pal Rituxan? In this small phase 2 study, 29 Follicular Lymphoma patients were given the -mab combo, and 19 of them (66%) had a response, with 15 of those 19 (a little more than half overall) having a Complete Response. That's pretty good.  Rituxan has about a 40% response rate, with 11% CR. So combining the two increases the effectiveness.

More importantly, it does so with about the same side effects as Rituxan alone.

So Pidilizumab certainly seems like a keeper. Obviously, a phase 3 trial, with more participants, is going to be the next step. There's some suggestion that maybe trying it on its own, in a trial with a direct comparison to Rituxan, might also happen in the future.

Certainly something else to keep an eye on. Maybe another arrow in the quiver.


Anonymous said...

more and more promising new treatments/combos in the pipeline! i remember you mentioned in one of your earlier posts that the next treatment in line if you ever need it will be bendamustine, is that still the choice? - Jeanne

Lymphomaniac said...

As far as I know, that's still the choice. I don't think I talked about it last time I saw Dr. R. I see him after the new year, so maybe I'll mention it again. He has also mentioned trying straight Rituxan again. It will depend on what we're dealing with, I guess. I'd also be open to a trial, which I've told him since I first started. You're right, though -- lots available in the pipeline.