Cancer Newsletter

I spend a  lot of time reading about cancer, as you probably know (or you can probably tell). 

I get lots of stuff in my email inbox about cancer, some of which I asked for, and some of which I did not. (I was contacted by a public relations aggregator years ago. They send press releases to journalists and bloggers, and they asked if I wanted to be included. I said yes, so about 20 times a day I get an email from someone pushing a product or a story related to "health" in some way. Very occasionally, it's something useful. Mostly it isn't anything that I want to write about. But I do enjoy knowing what is being pushed when it comes to "health."

One thing that I did receive that has been useful and interesting is a newsletter called Breaking Cancer News. That title sounds fake, to be honest. I fully expected it to be a newsletter full of stories about one product that was really questionable. But the first time I received it, I spotted a name that let me know it was legitimate. 

The name was Jamie Reno, who is the editor of the newsletter. He's also a long-time journalist who used to write for Newsweek and Healthline and a whole lot of other publications. I know the name because he has also been diagnosed with Follicular Lymphoma about 22 years ago. He wrote a book called Hope Begins in the Dark, which tells the story of 50 patients who were diagnosed with Lymphoma. And if my memory is correct, he was an early user of RadioImmunoTherapy (RIT).

So if it's cancer-related, and Jamie Reno's name is on it, I feel like I can trust it.

I signed up to get Breaking Cancer News sent to me once a week, and I am enjoying it (as much as someone can enjoy reading about cancer). The stories are written with a general audience in mind, so they're easy to understand (unlike most of the stuff I link to in this blog). And the stories deal with current issues, as the name of the newsletter suggests. Not necessarily about things like FDA approvals or clinical trials. More about issues that affect all patients, caregivers, and advocates.  

For example, in this week's issue, there's a short commentary from Jamie Reno about how politics is keeping a cancer funding initiative from being passed in Congress. Then there's a story on multi-drug resistance -- how cancer cells can find ways to survive multiple treatments, and what researchers are trying to do about it. And finally there's a story on some of the latest developments in cancer prevention and detection. 

None of this is about Follicular Lymphoma, specifically, but it does provide some interesting context on the larger issues that affect cancer patients and researchers. I like the big picture it provides me.

The header on the newsletter says it was developed in partnership with the organization Teen Cancer America, which focuses on helping young people who have been diagnosed. And the newsletter's tag line is "Plain talk about what's hot and hopeful in the cancer arena -- for young people and anyone else who's listening." But don't be fooled -- there's good stuff in there for all of us.

I don't have any affiliation with the newsletter or the organization that sponsors it. I've been reading it for a few months now, and it seemed like something worth sharing. I hope you'll find it interesting.

Improved Outcomes for Transformed FL

The journal Cancer Medicine  published a very interesting article lest month called "Outcomes of the transformation of follicular lymphoma to diffuse large B-cell lymphoma in the rituximab era: A population-based study." It describes a large research study that compared the outcomes for patients who were diagnosed with Diffuse Large B Cell Lymphoma (DLBCL), an aggressive type of Lymphoma, with those who were diagnosed first with Follicular Lymphoma and whose disease then transformed to DLBCL. There's lots of interesting data here, but the most important is this -- in the last 20 years, outcomes for FL patients with transformed lymphoma are greatly improved.

It is important to note that this is a "population study," meaning the researchers didn't look at individual patients. Instead, they looked at a large database called the SEER (Surveillance, Epidemiology, and End Results). You're probably in it -- oncologists upload anonymous data into the SEER database so this kind of large study can be done. Population study look at trends, rather than individual patients. But because they are looking at large numbers of patients, the results can be very interesting.

For this study, the researchers were interested in patients with transformed FL who were diagnosed between 2000 and 2020. This time period is known as "The Rituxan Era." Rituxan was approved by the FDA in 1997, and there were big improvements in FL patient outcomes once Rituxan started getting mixed with traditional chemo, and then with other treatments. As the researchers note, small studies focused on transformed FL are inconsistent in what they reveal, so they thought a large study like this would be helpful.

And it is indeed large. The researchers found 50,332 FL patients in the database who were diagnosed in that 20 year period, along with 95,933 patients who were diagnosed with primary DLBCL (in other words, they didn't have FL first). Of those 50,000+ FL patients, 1631 had disease that transformed. 

That in itself is very significant to me. When I was diagnosed (in 2007), I read in many places that as many as 50% of FL patients would end up with transformed disease, which was alarming to me. Over time, in the small studies that I read, the numbers would usually come as closer to 15 or 20%. That's slightly less worrisome. But in this large study, only 3.2% of FL patients transformed to DLBCL. That is, obviously, a significantly smaller number. 

(I'm not suggesting the old research was wrong, or the new research is wrong, or that transformation is no longer a big deal. Just that the smaller number is very surprising to me.)

In fact, it's important to note that one of the things the researchers make clear is that transformation has a serious impact on Overall Survival. For patients with transformed disease, the OS rate at 10 years was 56.6%, with a median survival of 137 months (a little over 11 years), with a range of 2 months to 21 years. For patients who did not have transformed disease, the 10 year OS was 64.8%,  with a median survival of 194 months (about 16 years), with the same range of 2 months to 21 years. So clearly, transformation is still a big deal.

But the larger point they're trying to make still holds true --  compared to the time before Rituxan, outcomes for transformed FL are better. 

A few other interesting bits:

• Patients who had received Radiotherapy or who Watched and Waited had better outcome after transformation than those who received traditional chemotherapy or a combination of chemo and radiation. (they don't get into why this might be so, but my guess is that it has less to do with the treatment itself and more to do with how aggressive the disease was before transformation. FL patients who watch and wait tend to have less aggressive disease; those who get chemo tend to have more aggressive disease. All of that is entirely my own, non-expert guess.)
• Patients whose disease transformed soon after their FL diagnosis (within 18 months) tended to do better than those with later transformation (after 18 months). I wonder if this had to do more with how long it took to discover the transformation, rather than the actual transformation. Again -- my non-expert guess.
  
• There are more options now for treating transformed FL, obviously. The recommendation used to be a Stem Cell Transplant. That's still an option, but no longer automatic, especially as more FL patients have traditional chemo "reserved" as a later possibility.

It's fascinating to me that, even 16 years after I was first diagnosed, we still have lots of unanswered questions about transformation -- and about so many other aspects of Follicular Lymphoma.  But despite the lack of answers, we are still seeing overall improvement as a group. And that's worth celebrating.

Patient-Derived Lymphoma Spheroids

That post title is a lot, but it's the subject of some very cool recent research on Follicular Lymphoma that might be a big help to us someday.

The Blood Cancer Journal just published an article called "Patient-Derived Follicular Lymphoma Spheroids Recapitulate Lymph Node Signaling and Immune Profile Uncovering Galectin-9 as a Novel Immunotherapeutic Target." There's a lot of science in that title, and even more in the article, but as I said, it's very cool research.

The article describes the use of something called a Lymphoma Spheroid. As the "sphere" in the name implies, it's kind of a ball of lymphoma cells plus some other things. And here's why it's important.

Before a cancer treatment can be tried out on people in a phase 1 trial, it needs to go through a whole bunch of "pre-clinical" steps. After a possible treatment is developed (and there's whole bunch of steps to go through with that, but that's another post), the next step is come up with a target for treatment, and then figure out if the new treatment will work on that target. This is usually done "in a test tube," mixing the treatment with some cancer cells.

But it's much more complicated than that. Think about it -- if I put some cancer cells in a test tub and then added some gasoline, the gasoline would almost certainly kill the cancer cells. But that's not helpful -- you wouldn't want to put gasoline into your body. It would kill all of your cells, not just your cancer cells. So you need a treatment that will work on the cancer cells but do minimal damage to healthy cells. That's a little bit more of a challenge.

Even then, it gets complicated. A treatment can work fine in a test tube, but then fail when it's given an actual patient. Why? A big reason is the microenvironment for the cell. This is everything that physically surrounds the cell. And the microenvironment plays a huge role in cancer cells surviving. People (you may have noticed) are not just individual cells; we are complex systems. Change one thing in a person, and you're likely to change a bunch of other things. You bang your toe, and soon your back hurts, because you're walking differently. With a sore back, you don't sleep well. Without sleep, you need more coffee. This makes you jumpy and you can't sit for long. this makes your sore back worse. 

You get the idea. Works the same for cancer cells. You try to kill a cancer cell, and something else gets in the way -- an immune cell, an enzyme, a protein. If it was easy to kill cancer cells, you wouldn't be here reading this.

The idea of a Lymphoma Spheroid is an attempt to deal with this challenge. It's been around for a few years, with some interesting research already being done with it.

Rather than just putting an FL cell in a test tube, the Patient-derived Lymphoma Spheroid attempt to create a 3D model of what's happening in the body -- recreating as best it can the microenvironment that the FL cell exists in. The researchers mixed together a formula with about 60% tumor B cells, and then added about 13% T cells that have the CD4 protein, and another 3% that have CD8. The researchers found that this mix kind of organizes itself into something that resembles what's happening in the patient's body, with the spheroid doing things like producing things like PD1 and CD3 that are already targets for treatments.

Just as important, it's showing that there are new targets for Lymphoma researchers to create treatments for, like CD39, a protein on the surface of the cancer cell. Some other research found that Obinutuzumab and Nivolumab, an anti-PD1 treatment, might be effective. 

The article from this week used Patient-Derived Lymphoma Spheroids to show that a protein called galectin-9 can lessen the effectiveness of Rituxan, and so they are proposing that galectin-9 would be a good target for future treatments. 

The most important thing with all of this is not just the "Lymphoma Spheroid" part of it, but the "Patient-Derived" part. Follicular Lymphoma is heterogeneous -- it shows up in very different ways for different patients. That's why there is no real agreement on what the best way to treat it is. But the Patient-Derived Lymphoma Spheroid takes cells from each patient. In other words, this isn't an attempt to study how FL behaves. It's an attempt to study how your FL behaves. We're all different, so recreating your personal microenvironment should, at least in theory, tell your doctor which treatments are likely to work best for you. that's what "personalized medicine" is all about.

Will this ultimately change things? Hard to say. Lots of cool things turn out to work less effectively than we'd hoped, once they get tested out on a large group of patients. But there's already a growing body of research that is showing some success. Time will tell.

But for me, getting (and sharing) a little bit more insight into the process for developing treatments is also the cool part. I often see (and share) research that is much farther along, and the closer it gets to the doctor's office, the more exciting it is. But there is a whole lot of work that goes into that journey from a test tube in a lab to an intravenous tube in a treatment room, and I like the reminder of that.

More good stuff to come. The ASCO abstracts are due out very soon....