Copanlisib for Follicular Lymphoma

A couple of Copanlisib-related items have come across my screen in the last few days, so I thought I'd share.

First, to remind you (since Copanlisib hasn't been in the news much lately, from what I have seen):

Copanlisib (also known as Aliqopa) is a PI3K inhibitor. PI3K is short for phosphatidylinositol-3-kinase, which is an enzyme that cancer cells depend on to grow and live. By inhibiting it, or stopping it, cancer cells don't get the signal that they should stay alive, and so they die. There are a few PI3K inhibitors approved for FL, but Copanlisib is thought to be better in one way -- it works on two of the three different forms of PI3K in the body (others only work on one of them). It has been approved by the FDA for relapsed FL patients who have tried at least two other treatments.

As I said, it's not in the news much lately, though it usually gets mentioned by name when lymphoma experts talk about non-chemotherapy treatments and the future of Follicular Lymphoma. (Search this blog and you'll see what I mean.)

The first thing that came around this week was an article from the journal Cancer Management and Research called "Copanlisib in the Treatment of Relapsed Follicular Lymphoma: Utility and Experience from the Clinic," written by Dr. Ayushi Chauhan and Dr. Bruce Cheson. (If you've been reading for a while, you know how much I enjoy Dr. Cheson's work.)

The article isn't describing new research. It's more one of those "here's where we are with things" articles.

Still, it's very helpful in that way. 

Copanlisib was approved by the FDA after only a phase 2 clinical trial, so it is currently in several phase 3 trials. These trials are looking at Copanlisib on its own, with others looking at it in combination with other treatment.

Interestingly, one of the other studies that the authors mention says that there is some evidence that Copanlisib is less effective due to insulin feedback. The treatment may set off a reaction that uses insulin to start the PI3K enyzmes that Copanlisib has inhibited, so slowing down insulin production during treatment may help it be more effective. One way of doing this might be through a keto diet, which I know a lot of people are interested in hearing more about. 

[But let me be very clear -- this article is not saying that a keto diet will stop, cure, or prevent cancer. It is being studied as a way of making one particular treatment more effective, and even that is just a theory. Don't stop eating bread because you think it will cure your cancer. There's no evidence of that. Talk to your doctor about your diet if you have questions.]

The rest of the article talks about the best uses for Copanlisib (it's a useful treatment for patients who have already tried two things and might get some use out of a different approach), and its future (like those trials that use it in combination with other treatments).

Which brings me to the second item that came across my screen recently: a quick video from Targeted Oncology featuring Dr. Mark J. Roschewski, who makes very quick mention of a different trial, this one a phase 2 trial that looks at Copanlisib with Rituxan in FL patients that have not yet had a treatment. I think this is probably part of a larger series of videos with Dr. Roschewski, but he is excited about this trial. So far, he says, every patient in it has had a response of some kind, with fairly quick reduction in the size of tumors. 

That's exciting, especially since the FDA approval was for relapsed FL. Good to see that it has some use in untreated FL, too. Options are good.

My guess is we'll see some of the results of these trials at ASCO in June. I look forward to it. (I'm happy about anything, really, that will get me through this winter and spring.)

More soon. Stay safe.

A New Approach to CAR-T?

The journal Nature Communications published an article last week called "CXCR5 CAR-T cells simultaneously target B cell non-Hodgkin’s lymphoma and tumor-supportive follicular T helper cells." It describes some early research from Germany on a new approach to using CAR-T. 

I won't give too much background on CAR-T, other than to remind you that this is a good site to visit to find out more about CAR-T and Follicular Lymphoma.

CAR-T works by using CD19 as a target. CD19 is a protein on the surface of many blood cells, including the cells that cause FL. When T cells are removed and "retrained" to recognize cancer cells, it's the CD19 protein that they go after. As the researchers point out, it's a successful target for CAR-T much of the time, but not always.

They found that there is another potential target -- a different protein called CXCR5. This protein is very important for those B cells, as well as some T cells that help some cancers stay alive. 

CXCR5 is kind of cool. When a blood cancer cells is developed in the bone marrow, CXCR5 helps guide them to the lymph nodes and the spleen, where they gather to help fight off invaders. Of course, when the cells become cancerous and refuse to die, they just hang out in the lymph nodes, causing them to swell up and make us panic. (Same thing happens in the spleen, which is common for some stage 4 Follicular Lymphoma patients, and the reason your oncologist pokes and feels around your belly at visits. He's not challenging you to a tickle fight.)

So CXCR5 makes sense as a target.

The researchers have found a way to develop CAR-T cells that target CXCR5 instead of CD19. It's going after the same cells as current CAR-T treatments, and would be created using the same process (removing T cells from the body and teaching them to find the cancer B cells), but would use a different target.

The The Max Delbrueck Center for Molecular Medicine in the Helmholtz Association (MDC), where the researchers work, actually put out a really nice press release on the research. Very well-written and clear, which isn't always the case with this kind of thing.

Important to note -- this is very early research. They've done some work in a test tube, and using mice, but it hasn't yet been tried on humans. They hope to get some clinical trials going soon. So even if it's successful, it could be a while before it's widely used. 

Still, I'm always up for a shot of hope, especially in these dark winter days.

Diagnosiversary Beach Day

Last Friday, I celebrated my 13 year diagnosiversary, as you may know.

It was a good day. Like most celebrations these days, it was not what I had planned, and not what I would traditionally have done. And that's OK.

(And, yes, it was a celebration. As I've said before, my wife always cringes a little when I say I'm "celebrating," and I always remind her -- we're not celebrating the day I was diagnosed, we're celebrating the 4789 days since that day.)

In the past, I have used January 15 as a day to "break the rules." I'm allowed, since it's my special day. That has usually meant staying home from work (that's one rule broken), going back to bed,  and the seeing an early afternoon movie with my wife. We'd buy sandwiches and sneak them in to the movie, breaking the "no outside food" rule. 

This year hasn't really been a "break the rules" kind of year. Most of the rules I can think of there are in place to keep me safe. No movie. Too risky. I won't go out without a mask, or get closer than 6 feet/2 meters from anyone. I needed to rethink my day.

We've all been very good about following Covid rules for months and months. Maybe this year we won't break rules, but we can at least break our routine?

We decided we'd take a little drive -- me, my wife, and the two kids who are still living at home (for a few more weeks, before they go back to school). I haven't driven longer than about 20 minutes in I don't know how long. So we took a drive to Hammonasset Beach, about 40 minutes from home.

It's the middle of winter here, and the temperature at the beach was about 40 degrees F (about 4 degrees C). That's the kind of rule I'm into breaking this year -- why go to a beach when it's sunny and warm?

But I really needed a beach for some reason. I needed to see some water. I've read that human beings are drawn to water, and being near it naturally brings peace. I believe it. I've lived near the ocean for most of my life (except for a few years in Louisville, Kentucky, which I loved despite its lack of salt water nearby). 

We stayed for maybe an hour, just walking on the sand, picking up shells, watching the birds, and talking. 

The beaches in New England (the part of the U.S. where I live) are not exactly world-class (too rocky for that), but they do the job just fine.

 

(That's me in the Cookie Monster hat.)

On the way home, we stopped for our usual sandwiches. It's not the same as sneaking them into a movie theater, but they were good anyway.

And my daughter was  good enough to make cupcakes that look like B lymphocytes (those are the white blood cells that turn cancerous in Follicular Lymphoma. Very satisfying to eat.)

 

All in all, it was a good day. Not the day I would have planned most years. But a good day.

And if cancer patients know anything, it's how to make the most of what you've been given.

Stay well, everyone.