Recent Treatment Guideline Updates [video]

A few weeks ago, OncLive did another of their short videos series, featuring oncologists exchanging ideas.

This one is called "Recent Treatment Guideline Updates in Follicular Lymphoma," and it features Dr. Sameh Gaballa of the Moffitt Cancer Center and Dr. Matthew Lunning of the University of Nebraska. (Unfortunately, there's no written transcript of the conversation, just a video.)

The two of them talk briefly about some of the changes that have been made to NCCN Guidelines. Those are the general guidelines for oncologists for which FL patients should receive which treatments, and in which order, if necessary. If you've been paying attention to FL research, you can guess that the guidelines are very flexible -- lots of options. That's good in a way, but less good because it means none of them are perfect.

Anyway, the two oncologists talk about how the guidelines have influenced their ways of diagnosing FL patients. 

Dr. Gaballa discusses testing patients for EZH2. It's an interesting idea -- as I mentioned a couple of posts ago, we have very few biomarkers that tell us that a particular treatment will work, but EZH2 is one of them. But relatively few FL patients have the marker, so it is limited in its usefulness. But for those who do have the biomarker, Tazemetostat is a good option -- especially for patients who have already had multiple treatments, given its less aggressive side effects.

They continue their conversation in a second video, "Evolving Treatment Landscape of Relapsed/Refractory Follicular Lymphoma." 

It's interesting to hear them talk about the kind of choices they make, and why. They are based on individual patients' needs, which is great, but also things like the recent pandemic, and making sure that their patients ' immune systems can handle the potential side effects of certain treatments.

It's a short, fast conversation, almost like sitting at a table in a restaurant and overhearing two oncologists talk about their work. But it's a very interesting bit of eavesdropping, and I always enjoy hearing oncologists get a little bit excited about what they do.

FLF Webinar: Close to a Cure?

The Follicular Lymphoma Foundation has posted the video of its second webinar on their web page. The webinar is called "How Close Are We to Curing Follicular Lymphoma?" 

It's definitely worth watching. And I'll spare you the suspense for an answer -- we're on the right path, but not really close. As in, we're at least a few years away.

The webinar features Dr. Mitchell Smith, who is the Chief Medical Officer for the FLF, along with Dr. Loretta Nastoupil from MD Anderson. At one point, they are interviewed by Nicky Greenhalgh, who founded the Living with Follicular Lymphoma group on Facebook (I know some of you are members of the group, as am I.)

As the speakers acknowledge, it's kind of difficult to determine if or when FL is "cured." It's not like other cancers, where very often, someone who has been in remission for 5 years is considered cured. With FL, many patients get 5 or more years of remission, but then have the very slow-growing disease show up again. So traditional notions of "cure" don't really apply.

Some oncologists (including the two speakers) refer to "functional cure" for FL. This means a patient might still have the disease, or still has a chance of it returning, but lives a normal life expectancy with a decent quality of life, and dies with the disease rather than from it. It's not hard to imagine -- a 65 year old person in the U.S. is diagnosed with Follicular Lymphoma (let's say grade 1, stage 3 for this example). Didn't know she had it. She watches and waits for two years, then has R-Bendamustine and gets 10 years of remission. Some nodes pop up, but not enough to treat, and stays that way for 2 years. So that's 2 years + 10 years + 2 years = 14 years living with the disease. 65 years old + 14 years = 79 years. Just about a normal life expectancy. 

Was she cured? No. Did she live with the disease in such a way that she might as well have been? Some would say Yes.

Of course, I say this as someone who has gone 13 years without treatment. I've never had a clean scan -- there has always been a little disease luring about. So I don't consider myself cured, and I expect that at some point, I'll need treatment again. I am nowhere close to a "normal" life span, but I expect to love that long, at least.

The speakers identify some of the things that make a cure so difficult. One big issue is the lack of "patient-specific tools." Because FL is so heterogeneous -- it's almost like a different disease for each patient -- it's hard to think of one thing that will result in a cure. It's more likely that we'll have a bunch of different treatments that result in long-term remissions for different patients. What works for me might not work for you.

But for that to happen, we need to identify biomarkers -- a gene or a protein that can be targeted with a specific treatment. But different patients will have different biomarkers, so one treatment won't work for everyone. Researchers are having a really hard time identifying those biomarkers. But they're making some improvements. 

Another problem is figuring out why FL keeps coming back. Is it because some cells are missed by treatments, but they are too small to see on a PET scan? (Maybe a liquid biopsy will help with that, but we don't have an accurate one ready yet.) Or is it that all of the cells are wiped away by treatment, but there is some mechanism that is untouched by treatment that causes new cancer cells to form later? Obviously, knowing the answer to that question will help with a cure.

So, an interesting webinar. It raises more question than it answers, really, but it does give a good sense of which questions we still need  to know more about. And that's not a bad thing.

If you can find 45 minutes for the webinar, it's worth the time. Aimed at patients, so it's fairly easy to understand.

SYMPHONY-1 Trial (Tazemetostat plus R Squared)

OncLive has a nice interview with Dr. Jennifer Effie Amengual of the Columbia University Irving Medical Center in New York. She discusses the SYMPHONY-1 trial, which is testing a promising treatment combination -- Tazemetostat plus R Squared.

Tazemetostat was approved by the FDA a few years ago for a subset of Follicular Lymphoma patients. Tazemetostat is an EZH2 inhibitor. EZH2 stands for "Enhancer of Zeste Homolog 2. EZH2 is an enzyme that is controlled by the EZH2 gene that controls tumor growth. Because Tazemetostat is an inhibitor, it stops EZH2 from allowing cancer cells to grow. 

As the interview with Dr. Amengual points out, one of the great things about Tazemetostat is its safety profile -- the side effects are comparatively mild (at least compared to traditional chemotherapy). To be clear -- there are side effects, and they can be serious. But they seems to be different from, say, CAR-T, especially cytopenias (that is, low blood cell counts, whether they are red or white blood cells or platelets). 

And that seems to be why the combination with R-Squared is appealing. R-Squared, as you may know, is the combination of Rituxan and Revlimid (also known as Lenalidomide). As I mentioned in my last post, R-Squared is a big deal because it was the first treatment that was shown to be as effective as traditional chemo, but with different side effects.

So you can see the pattern here -- effective treatments with different side effects that don't pile up on each other. 

One of the interesting things that Dr. Amengual discusses is a kind of comparison between this combination and CAR-T. The trial doesn't specifically compare the two, but she does bring up which patients she would recommend for each of them. She uses the phrase "younger, fit patients" to talk about who she might recommend CAR-T to. Particularly because CAR-T patients had likely been heavily pre-treated, already having received a few treatments already that would have potentially weakened their immune systems, a combination like Tazemetostat and R-Squared might be easier on older, less fit FL patients. 

The trial is now in phase 2, so they are testing how effective the combination is. Half of the patients in the trial will get Tazemetostat and R-Squared, and the other half will just get R-Squared. Definitely worth paying attention this one.

The interview on OncLive seemed pretty accessible to me, if you're interested in reading it. It's worth a look. 

Update on Follicular Lymphoma

The medical journal Hematological Oncology published a great article last month called "Update on Follicular Lymphoma." I like articles like these, and I try to link to them when I can. They aren't presenting any new research; they're just trying to say "There's a lot going on with FL, so let's stop and take a look at where we are."

This particular article keeps its focus on what has happened over the last 3 years, and it highlights six particular things that should give us all hope. I won't give too much commentary on them, since I've written about all of them in the blog (I'm linking to my blog posts, which you should be able to use to find further links with more information). But it's nice to see them all in one place. You can read the article for more detail.

Here are the six things that the article highlights.

1) Bone marrow biopsies are not necessary for most patients with FL. The research actually focused on Bone Marrow Biopsies in clinical trials, but the general lesson is pretty much the same -- Bone Marrow Biopsies are awful, and they probably don't tell us anything more than other diagnostic tests tell us. There seems to be a growing movement to do away with them.

2) Validation of POD24 status. POD24 refers to the idea that patients who have Progression of Disease (POD) within 24 months of receiving immuno-chemotherapy (like B-R or R-CHOP) tend to have a lower median rate of survival. Within the last 3 years, research has confirmed that POD24 is valid. The good news is that this has created more research on this population of FL patients (it affects about 20% of us), which hopefully will help identify them earlier (right now they are only identified when the disease progresses), and those biomarkers might lead to new treatments for them.

3) Long-term follow up of the RELEVANCE trial for R-Squared. The RELEVANCE trial showed that R-Squared (a combination of Rituxan and Revlemid/Lenalidomide) was as effective as traditional chemotherapy for Relapsed and Refractory FL patients. (It also has a different set of side effects -- not better safety, but different.) This was the first treatment that showed that a non-chemotherapy treatment could be as effective as chemo. A big deal. 

4) Response-Adapted Treatment is not Superior. I'm a little surprised that this one made the list, but it's important. It describes research that compared Rituxan Maintenance with response-adapted treatment (basically, that you don't treat someone a second time until they shows signs of needing treatment). The researchers had guessed that response-adapted treatment would be better than Maintenance (fewer side effects, less cost). But they found that PET scans didn't always pick up the returning disease, so Maintenance might be a better option -- or at least as good an option. Not much follow-up on it, though, from what I can tell. Maybe that's coming soon.

5) The Bi-specific Mosunetuzumab is pretty great. I assume I don't need to get too much into this.

6) And so it CAR-T. Same here.

As I said, none of this is new research. But it's great to see all of these positive developments in one place. As the authors point out, these developments aren't the end. In almost every case, they are the beginning of additional research that could change our lives for the better, in a number of ways -- focusing research in new directions, improving our quality of life, or even (dare I say it?) moving closer to a cure.

I'm looking forward to sharing six more great advances a few years from now. I know they'll be coming.

Dogs and Cancer

Interesting article from Pharmacy Times a few weeks ago called "Canines Are Leading the Fight Against Human Cancer." It spells out how a cancer clinical trial for dogs has led to some treatment options that can be used on humans.

The cancers come from what are called RNA Neoantigens. When cells divide, they rely on RNA (Ribonucleic Acid -- this is all coming back to me from the Biology class I took in my first year in college). When problems arise with RNA, they can start a process that can lead to certain cancers. The trial using dogs is for a vaccine that might prevent several cancers that start this way.

Dogs do develop cancers. As the article points out, dogs over 10 years old have a 50% chance of developing cancer at some point. SO finding volunteers for a cancer clinical trial isn't hard. (People do love their dogs, and are willing to sign them up.) About 800 dogs are involved in this cancer vaccine trial. It's a 5 year trial, but early results are promising.

And the hope is that not only will this help some dogs, but will also lead to discoveries that will help develop cancer vaccines for humans. 

All of this made me think about the other ways that dogs help with cancer patients.

The one that stands out most for me is cancer-sniffing dogs. This is because the first cancer-sniffing dog was a standard schnauzer named George. I know this because a year before I was diagnosed with Follicular Lymphoma, we got a standard schnauzer named Strudel. For all of Strudel's good points, she was never a cancer-sniffing dog. So, not very helpful. But she was very cute, as you can see from the picture below.

Of course, dogs are also just wonderful by their very presence, and there is some research that suggests that having a dog can help lower someone's blood pressure and generally have a healthier heart. So after we lost Strudel a few years ago, we got another standard schnauzer, this one named Katara. So with this little heart-healthy pet, I was surprised to develop high blood pressure and some heart issues. I guess this one isn't much help when it comes to my physical well-being, either.

But, again, she's awfully cute, as these two pictures show.

I hope those of you with pets have a better time having them support your health. Whatever the case, give them extra hugs today and maybe an extra treat.

And be thankful for those other dogs that are helping all of us.

(Posting pictures and stories of your pets in the comments is always welcome.)

Phase 2 Trial Results for Liso-Cel CAR-T

I write about CAR-T treatments a lot, and it's easy to forget that CAR-T is not just one treatment. Instead, it's a general name for a bunch of different treatments. They all work in the same way, but they are different, made by different companies, with slightly different effectiveness and safety. It's kind of like using "chemotherapy" as a general term, though there are probably 10 different chemo combinations that have been used for Follicular Lymphoma over the years.

At the moment, there are two different CAR-T treatments approved for FL patients.  The first is Tisagenlecleucel, also known as Kymriah. The other is Axicabtagene Ciloleucel, also known as Yescarta. They are both approved for Relapsed/Refractory FL. There are many others in development (as I wrote about in February).

One of the CAR-Ts that already has some approvals is Lisocabtagene Maraleucel, also known as Liso-Cel or Bryanzi. This version of CAR-T has been approved in the U.S. and Europe for more aggressive lymphomas like DLBCL, but also for grade 3b Follicular Lymphoma, which is sometimes described as being very like DLBCL. But for the great majority of FL patients, Liso-Cel is not yet available.

But like many treatments that are approved for one blood cancer, Liso-Cel is in clinical trials for others, including Relapsed/Refractory FL. It's currently in a phase 2 clinical trial called TRANSCEND FL. The results were reported at the International Conference on Malignant Lymphoma in June. 

OncLive published the results. The patients included some with more than three previous treatments, and some that were POD24. Patients first received lympho-depleting chemotherapy (a round of chemo to help reduce the number of cancer cells). 

As of January 27, 2023 (the cut off for the data to be analyzed), 130 patients received Liso-Cel and 124 were able to be evaluated for the study. The Complete Response Rate was 94.1%. After 16.6 months, the median Duration of Response had not been reached, and neither had the median Progression Free Survival after 17.5 months. (In other words, fewer than half of the patients in the study had their disease return by that point.)

For safety, the most serious side effects were related to blood levels. The most common was neutropenia (low white blood cells), with 65% of patients. Cytokine release syndrome (CRS) happened in 58% of patients. There were nerve issues in 15% of patients. There was one death in the group.

As with other CAR-T treatments, Liso-cel looks safe and effective, and may very well end up as another CAR-T option for FL patients. That may take a few more years as trials continue. Another one to keep an eye on.