Tuesday, October 20, 2015

Targeted Approaches to Follicular Lymphoma

Cancer Network  published a review article from Dr. Chaitra Ujjani a few days ago called "Targeted Approaches to the Management of Follicular Lymphoma." I think it's as good a summary of where we are with FL treatments as you're going to find -- pretty up-to-the-minute stuff.

Dr. Ujjani attempts to describe the targeted approaches to Follicular Lymphoma that are out there, either as approved treatments or in various stages of clinical trials. "Targeted" basically means a treatment that doesn't try to kill off cancer cells the way traditional chemotherapy does, but instead uses our understanding of how cancer cells grow and survive to attack those processes. The "target" isn't the cancer cell, but the things that let the cell live, usually unique to that type of cell.

The article opens with a basic understanding of how Follicular Lymphoma has usually been treated with chemotherapy, and of how that understanding has changed what we know, and how we treat it.

The article then goes on to describe the different types of treatments, how they work, and how successful they have been so far. Before I get into some of those types of treatments, I want to share a table from the article that lists those treatments:

Targeted Approaches to the Management of Follicular Lymphoma - See more at: http://www.cancernetwork.com/oncology-journal/targeted-approaches-management-follicular-lymphoma#sthash.yijmoBYx.dpuf

That's a pretty nice list. Even if you don't understand any of what is on the list, it's pretty cool to see just how many treatments are out there in various stages of development. Even if half of them, even one quarter of them, were eventually approved, we'd have a bunch more options than we have now. That's just a chart full of hope right there.

As for the specific types of treatments, Dr. Ujjani gives a nice description of them:

Newer Anti-CD20 Monoclonal Antibodies: The granddaddy of targeted FL treatments is Rituxan, which has really changed FL patients' lives in amazing ways. Rituxan targets CD20, a protein on the surface of FL cells. As amazing as Rituxan is, it has its problems, and researchers are working on alternatives to Rituxan that can be even more successful with fewer side effects. These include Ofatumumab and Obinutuzumab, which have approved for CLL, but not yet for FL.
ofatumumab and obinutuzumab
ofatumumab and obinutuzumab

Monoclonal Antibodies to Alternative Targets: CD20 isn't the only protein on FL cells that can be targeted. Others include CD80 and CD22. But most promising seems to be antibodies that target CD19. There are a couple of treatments in development that target this protein.

RadioImmunoTherapy: I've written a lot about RIT, and how underused it is (for lots of reasons that seem to have more to do with how it is administered than how effective it might be). RIT involves putting a dash of radiation onto a monoclonal antibody, so the radiation can be delivered directly to the FL cells.

Antibody-Drug Conjugates: ADCs are sort of like RIT, in that they involve using something like a monoclonal antibody that can track down an FL cell, and attaching a small bit of a drug to it, so that the drug is delivered directly to the cancer cell. So instead of traditional chemo, which will kill any cell in its path, the ADCs make sure only targeted cells get the drug delivered to them. The article mentions four ADCs in development.

Tumor Microenvironment: These treatments don't focus on the cancer cells themselves, but on the stuff happening around the cell that is necessary for the cell to survive. An example of this is Lenalidomide, also known as Revlimid. Lenalidomide can affect cancer cells directly, but it can also mess with stromal cells in the bone marrow, which support the blood cells. So tumor microenvironment targets mess with things that support the cancer cells, and not necessarily the cells themselves.

Small-Molecule Kinase Inhibitors: Finally, there are the various Kinase Inhibitors, like Idelalisib. These treatments inhibit certain enzymes from doing their job. These enzymes are usually messed up, and allow cells to grow much longer than they are supposed to. By inhibiting them, they keep cancer cells from growing too large and too long. These treatments are a big step beyond chemo as well because they show that a cell cam be stopped by shutting down important parts of the cell, rather than killing the cell outright.


You can learn more about the different types of treatments by reading the article.

One important thing to remember -- as inspiring as it is to see all of these treatments in one place, they are almost all still in development, working their way through clinical trials. Which makes me think of something I read once from Karl Schwartz, President of Patients Against Lymphoma/ Lymphomation.org: all of these treatments are useless if patients don't volunteer for clinical trials themselves. Great treatments don't get approved if they haven't been shown to work, and the only way to show that is to test the treatments on patients. Something to think about if you ever need treatment (though we also hope that doesn't happen for a long time, or ever).

In the meantime, we have much to be hopeful about.


William May said...

I was surprised that this great article did not mention auto or allo transplant - I wonder why?

Lymphomaniac said...

William, I think, given the focus, the author wouldn't include that as a "targeted" therapy. I don't think it was meant to discuss ALL options, just the ones in that "targeted" category.