Tuesday, October 28, 2014

Ixazomib (Another Inhibitor)

The Blood Cancer Journal recently published the results of a phase I clinical study on Ixazomib, a proteasome inhibitor. It showed some promise for use on Follicular Lymphoma.

The article compares Ixazomib to Bortezomib (also known as Velcade), which was the first proteasome inhibitor to get approval. (It was approved for Mantle Cell Lymphoma, though some clinical trials for Follicular Lymphoma have looked good.) Bortezomib/Velcade works by blocking proteasomes, which help keeps cells healthy by getting rid of older and messed-up proteins. Protease inhibitors block that process in cancer cells, so all of those messed up proteins pile up in the cell and cause it to die.

Ixazomib will work in a similar way, though it has a different structure than Bortezomib/Velcade, which the developers hope will result in greater effectiveness and fewer side effects.

The phase I trial was meant to test whether or not it would work on certain types of lymphomas, to measure side effects, and to determine what the ideal dose would be. Of the 26 patients who went through the trial, 11 had Follicular Lymphoma, and 4 of them had a response. This is good enough to move on to a phase II trial.

The usual warnings apply here:

Phase I is very early. There will be a lot of time between now and when (and if) this gets approval, and clinical trial volunteers will be needed. It will also face the hurdle of needing to show it is better than what we have now, with Velcade. A response from 4 out of 11 FL patients is good, though not overwhelmingly good. We've seen a few  monoclonal antibodies try to outperform Rituxan, and so far no one has hit on the magic formula that will do that. Will the same thing happen with some of these attempts to improve various inhibitors?

We shall see.


Anonymous said...

Bob, I am your regular reader thanks for writing. I log on everyday to see what new treatments we have out there or in the making. You keep us so updated thanks again.if you can please let me know other than rituxin what other monoclonal antibodies we have that can be used that are fda approved as treatment outside clinical trials. That insurances will cover. I have already had rchop to treat my grade3a fnhl in stage 2, am thankfully in remission and on maintanence. Always worried that it will come back tomorrow or who knows when. Worried but hopeful. Thanks please keep writing.

Evan said...

Interesting article... never heard of TGR-1202 and ublituximab. FL is mentioned in this article: http://www.onclive.com/conference-coverage/cfs-2014/TGR-1202-and-Ublituximab-Show-Promise-in-CLL

Lymphomaniac said...

Sorry it's taken a while to respond. Here's a nice article with a rundown of antibodies that have been approved for various blood cancers:

Be warned -- it's over a year old, and I don't know where all of them are in terms of clinical trials and approvals. But it's a good start if you want to do some googling on your own. There may be a similar list out there that's more up-to-date.
Hope this helps.

Anonymous said...

Thank you Bob truely appreciate your input.