Friday, June 19, 2015

Temsirolimus for Follicular Lymphoma

The journal Cancer has published an early preview of an article called "A Phase 2 study of Weekly Temsirolimus and Bortezomib for Relapsed or Refractory B-cell Non-Hodgkin Lymphoma: A Wisconsin Oncology Network Study." 

The study involved Temsirolimus, also known as Torisel, and Bortezomib, also known as Velcade.  The two treatments are both in the general category of "inhibitors," meaning they keep something from happening -- something that cancer cells need to happen.

We already know about Bortezomib/Velcade. It's been around for a while, and is approved for use with a couple of other blood cancers, and has been in some trials for Follicular Lymphoma. It is a proteasome inhibitor, meaning it keep proteasomes from working. Proteasomes' job is to break down proteins in the cell when they are no longer needed -- kind of like taking out the garbage. When they stop working, the proteins don't get broken down. Instead, they pile up and basically kill the cell from the inside.

I don't know much about Temsirolimus. It has been around for about as long as Velcade has, but it is usually used on renal cell carcinoma, a cancer of the kidneys. It is another type of inhibitor, a Rapamycin Inhibitor, sometimes called a mammilian target of rapamycin (or mTOR) inhibitor. Like other inhbitors, Temsirolimus messes with the processes that cancer cells need to happen in order to survive. In this case, Temsirolimus messes with mTOR, which seems to be an important target, since it controls a lot of other processes inside the cell that determine its survival. If the enzyme is blocked by Temsirolimus, important stuff doesn't happen, and the cell can't grow and survive.

So these two different treatments, Temsirolimus and Bortezomib/Velcade, block different things that are both important to the cell. Combining them seems like a smart strategy -- a double attack on the cancer cells, coming from two different directions.

The phase 2 study described in the article involved 39 patients with different types of B-cell NHL, including Follicular Lymphoma. All 39 patients were heavily pre-treated -- they had already received different treatments, which either stopped working or didn't work in the first place. Of the 39 patients, 3 had a Complete Responses and 9 had a partial Response.

Overall, the patients had a median Progression-Free Survival of 4.9 months. However, the median PFS for the 9 patients with Follicular Lymphoma was 16.5 months, more than three times the median for the entire study.

The authors of the study believe the results justify further study of this combination for patients with  different types of NHL, especially Follicular Lymphoma.

There is certainly some cause for hope here, though it is important to remember that this is a very small study, especially the number of Follicular Lymphoma patients (just 9). What does give me reason for hope, though, is that we have more data here for the effectiveness of inhibitors in general. This type of treatment seems like it will play a big part in our near-term futures as Follicular Lymphoma patients, and the more we can learn about them, the better off we will be in figuring out which ones work on FL, which work best together, and which combinations might make sense to try in the future.

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