Treatments for Relapsed and Refractory FL

Every now and then, someone will publish an article that lists the treatments available for Follicular lymphoma patients. It's nice to read. Even if there's nothing new on the list, I always feel better having it all laid out in front me, knowing what's out there if (when) I need it.

Best Practice and Research: Clinical Oncology has gathered some recent articles on indolent lymphomas into its March 2018 issue. A few of them look at Follicular Lymphoma, including one of those articles that lays out treatment options.

It's called "Novel Agents for Relapsed and Refractory Lymphoma," written by Dr. Chan Yoon Cheah and Dr. Nathan Fowler. As the title says, the focus is on treatments for patients who have already been treated at least once, and either did not have a response to the treatment, or who had a response and then had the FL come back.

(Since I've already had treatment, I'm especially interested in all of this.)

The article starts out with a description of indolent lymphomas like FL -- slow-growing, often manageable, usually incurable. Ideally treatment will result in remission that lasts a long time and allows for a good quality of life.

The authors recommend that, if a relapse is suspected, a new biopsy be taken, to make sure the FL has not transformed into a more aggressive form. If it has, then there's a whole different set of considerations (and a whole different article to look at in this issue of the journal).

If there is no transformation, then there are a bunch of options: if no organs are threatened and there are no problems, then watching and waiting is OK. If treatment is necessary, they recommend that patients go into a clinical trial "whenever possible."

That's worth repeating. Patients should consider clinical trials whenever possible. If the symptoms are not life-threatening, then a trial may end up giving a response. If not, there's probably time to try something else (again, the relapsed FL isn't aggressive). And at the very least, the patient has helped us all by trying out something that might be approved for the rest of us (or might not -- that's valuable, too).

From there, the authors list some options:

• Anti-CD20 Monoclonal Antibodies. Rituxan is the biggie here, but Obinutuzumab has been recently approved. They work on their own (I had straight Rituxan), or in lots and lots of combinations with other treatments.
• Lenalidomide. Also known as Revimid, and R-squared when combined with Rituxan. Lenalidomide worked just OK on its own, but it has been great in that R-squared combination. I think it's one of the treatment that gets lymphoma specialists most excited. 
• PI3K Inhibitors. Idelalisib is the one they focus on most, though they also mention Copanlisib and Duvelisib. While these inhibitors have been successful, the authors also point out some serious side effects.
• BTK Inhibitors. Like other inhibitors, these stop (or inhibit) processes that cells go through in order to grow and survive. Ibrutinib is their main example, though there are some others in development. BTK inhibitors are another treatment type that seems to work better when it is combined with something else. (That's a big theme these days.)
• Bcl-2 Inhibitors. Again, these treatments stop cancer cells from doing the things that the immune system can't. Venetoclax is their main example here.
• Antibody Drug Conjugates. Monoclonal antibodies like Rituxan work by seeking out a protein on a lymphoma cell and attaching to it. A conjugate takes advantage of that -- while the antibody is attached, it delivers something else to the cell to kill it. 
• Epigenetic Therapies. This is another group of inhibitors, thugh it targets something different than the ones above. Vorinostat is an example (though it is one that seems to work well on its onw, instead of in combination with something like Rituxan). Abexinostat and Tazemetostat are two others.
• Immune Checkpoint Inhibitors. Nivolumab and Pembrolizumab are two examples. Another type of inhibitor, this one stops something that stops something else. The result is that the immune system is able to find and attack lymphoma cells.
• Chimeric Antigen Receptor T Cell therapy. Also known as CAR-T, which has been in the news quite a bit lately. T cells, part of the immune system, are removed from the patients and changed so that the T cells recognize the lymphoma cells as something that doesn't belong. A very promising treatment. Read more about it at CAR-T and Follicular Non-Hodgkin's Lymphoma, the blog run by our friends Ben and Will.

Note that these are novel agents -- new ones. You may have noticed that they don't even inlcude chemotherapy, RIT, and some other treatments that have been around for a while.

A couple of trends -- lots of these treatments seem to work better when they are combined with others. And lots of newer treatments are kind of anti-chemotherapy -- instead of trying to kill the cancer cells directly, they try to to stop (inhibit) other things from happening that the cancer cells need in order to survive.

The good news with this list is that there are a lot of options being tested for us. Some of them will end up working, though not all of them will.

And it's important to remember that all of these treatments come with side effects. They might be anti-chemo, in a way, and more targeted, but that doesn't mean they won't cause some problems. Ideally, researchers are finding ways to make sure the problems aren't as bad as the solutions -- the success of the treatment is worth the side effects.

Lists like this are valuable because they give you something to talk about with your doctor, if and when the time comes to treat.

And it's worth repeating -- none of this stuff becomes available to patients until it goes through a few clinical trials and then gets approved. "Whenever possible," we should think about participating in clinical trials, and helping to make it all happen.