Lenalidomide and Secondary Cancers

Since I've been thinking and writing about secondary cancers lately, I thought I'd share this: "Second primary malignancies in patients with haematological cancers treated with lenalidomide: a systematic review and meta-analysis," published a couple of days ago in The Lancet Haematology.

I'll give you the good news up front -- Lenalidomide doesn't seem to cause secondary cancers in Follicualr Lymphoma.

Lenalidomide is also known as Revlimid, and it is the second "R" (along with Rituxan) in the combination R-Squared. This treatment is, of course, an important option for Follicular Lymphoma patients, since it is the first non-chemotherapy treatment that has been shown to be as effective and safe as traditional chemo like R-CHOP or B-R. Safety is important -- in the study that compared R-Squared to chemo, it was found that R-Squared had about the same amount of side effects, but different ones. 

One long-term side effect of any cancer treatment is the potential for developing secondary cancers -- a new cancer other than the one being treated. They happen, because many cancer treatments work by affecting the DNA of cancer cells, and sometimes normal cells, too. When a normal cell's DNA is changed, it can change in bad ways, making it hard for the cells to die a natural death, and thus become cancer cells.

So that brings us to the Lancet article.

Lenalidomide has been used for a while to treat Multiple Myeloma, another blood cancer that shares some characteristics with FL. It can grow slowly, for example. When I was a guest on the No Better Time Than the Present series (see the YouTube video here), I talked a little bit about how much I could connect with my host Yolanda's experience as a patient with Multiple Myeloma. Yolanda watched and waited for 5 years before treatment, for example, way more than my 2 years.

Whole Lenalidomide can be effective for for Multiple Myeloma, several studies have shown that it increases the the chances of secondary cancers for MM patients. But, as the researchers say, there hasn't been a careful look at whether Lenalidomide increased the chance of secondary cancers for other blood cancers and blood disorders that use it as a treatment.

So they did what's called a meta-analysis. Instead of running a brand new clinical trial, they looked back at the data from every bit of research they could find that studied Lenalidomide. They found a whole bunch -- 38 trials that included 14,058 patients, including 18 trials with patients with Multiple Myeloma.This allowed them to compare MM with other blood cancers.

The results were kind of fascinating. Patients with MM had a higher incidence of secondary cancers, both new blood cancers and new solid cancers. But patients with other blood diseases -- lymphoma, CLL, or myelodysplastic syndrome -- had no increased chance of secondary cancer. 

That's good news for us. I can only see the abstract of the article, not all of the data, so I don't know if they broke out Follicualr Lymphoma studies specifically. But I don't think that matters for the results. At least according to research that has already been published, Lenalidomide does not increase our chances of a secondary cancer. 

It's not good news for Multiple Myeloma patients, of course, and I feel for them. But I also find it fascinating that there is something about MM that mixes with the mechanisms of Lenalidomide that just isn't present in FL or other lymphomas. I'm sure lots of Lymphoma experts will find that even more fascinating, and that's great news. A new line of research that might help them understand MM a little bit more.

One less thing to worry about....

A Tool for Predicting POD24 in Follicular Lymphoma?

 Very cool research from Spain, published in Clinical Cancer Research this week, in an article called "Monitoring of circulating tumor DNA predicts response to treatment and early progression in Follicular Lymphoma: results of a prospective pilot study." It has some potential implications for POD24 patients.

Lots of background before we get to the article.

POD24 stands for "Progression of Disease within 24 month." It's the name for what happens when an FL patient receives immunochemotherapy (like R-CHOP or B-R) and has a response, but then relapses (has progression of the disease) within 24 months. Research shows that this happens to about 20% of FL patients. Research also shows that, unfortunately, POD24 patients have a lower median 5 year survival rate than other FL patients. It was a fairly big deal that researchers were able to identify this group of patients, and lots of Lymphoma experts think that the Lymphoma Research Community needs to focus its attention on helping this group. And lots of researchers have done that.

Now, a separate bunch of researchers are working on "Liquid Biopsies." I'm sure we are all familiar in some way with "solid" biopsies, where a sample of possibly cancerous cells is taken from out body. Maybe this is with a fine needle aspiration (not fun, but the least painful option now available). For others -- me included -- this meant surgery to remove a lymph node, and/or a bone marrow biopsy to get inside a bone and remove some of the inner material. (I had both of those.) "Solid" biopsies are not fun. They are invasive and painful.

(Sorry -- I probably didn't need to remind you of that.)

With a liquid biopsy, a sample of blood is taken and analyzed to see if there are any tiny cancer cells floating around. They're called "circulating tumor DNA" or ctDNA because they float around in the blood, too small to be picked up a scan, and not gathered up in a lymph node in a big enough group to justify a solid biopsy. But they are still there, in very early stages. A "liquid biopsy" can find them, early, without all the cutting.

I wrote about liquid biopsies a few months ago, looking at an article that basically laid out what we knew about them so far, and how promising they were.

So bring those two things together now: some researchers in Spain have done a prospective study that uses liquid biopsies to find circulating tumor DNA to predict POD24. This is excellent news.

The researchers looked at samples of plasma (the liquid part of the blood) from 36 patients with Follicular Lymphoma. The patients came before, during, and after treatment (they had immunochemotherapy). Then they followed the patients for a median of about 3.5 years. The goal was to see which of the patients turned out to be POD24, and to then look at the plasma samples to see if there was any ctDNA in the samples, and whether that could have predicted the POD24.

What they found was that, yes indeed, the liquid biopsies could find the ctDNA and could predict that some patients would relapse early. There was a clear difference in the samples of POD24 patients and patients who did not have a Complete Response to treatment, compared to non-POD24 patients and those who did achieve a CR.

From this, they think their method for identifying ctDNA could be used during clinical trials to monitor patients, and could one day be used in clinical settings, allowing FL patients to monitor their status with a blood test, rather than a scan (or a solid biopsy).

Of course, the important words in the title are "prospective pilot study." This was a small sample of patients, not in an "official" trial setting. So it shows a lot of promise, but it's not something you're going to see in the doctor's office anytime soon.

I do think its important, though, to recognize that researchers are becoming more and more conscious of not only the importance of dealing with POD24, but also of just paying attention to Quality of Life for all of us.Liquid biopsies won't cure anything, but they will make the experience of living with FL a  little bit less unpleasant. And that's worth a lot.

Cancer Vaccine by 2030?

Earlier this week, I saw a whole bunch of news stories about a possible cancer vaccine being available by 2030. I'm skeptical. (But that's just how I am.)

I'm actually less skeptical the more I think about it.

The vaccine possibility came during an interview with Dr. Ozlem Tureci and Dr. Ugur Sahin, the married researchers who founded BioNTech, the company that created an mRNA Covid-19 vaccine with Pfizer.  

I'm skeptical because I'm always skeptical by anyone who claims they might find "a cure for cancer," as if cancer were one disease. It's certainly not -- even Non-Hodgkin's Lymphoma isn't a single disease, and has up to 80 subtypes. And even within a single type of cancer, the pathways that cancer cells use to stay alive, and the microenvironment factors that they take advantage of to grow -- it's all just mind-blowing to think about. Cancer cells find a way to avoid treatment, to come back from treatment, and to find new ways around treatment. Finding one way to stop a cancer cell is a very difficult task. Finding one way to stop ALL cancer cells, no matter the type, just seems impossible. 

And yet....

Apparently, Drs. Tureci and Sahin were originally working on an individualized cancer vaccine when their mRNA technology was needed for Covid. Now they're back to the cancer vaccine.

It is individualized, something like CAR-T. As they describe it, after surgery to remove a tumor, the patient would receive a vaccine that recognizes the cancer cells. It uses T cells (like CAR-T) to scan the body for cancer cells and eliminate them. Like CAR-T, in theory, the T cells will have a memory so that if the cancer cells come around again, the T cells will find them.

It's an interesting concept, and to me, the fact that it is individualized is what makes me slightly less skeptical than I would be about some other "cures for cancer."

And, of course, it's important to go beyond the headline and look a little closer. Lots of stories have "cure" in their headline to catch people's attention, but a quote from the interview is important:

"Yes, we feel that a cure for cancer, or to changing cancer patients' lives, is in our grasp," said Professor Ozlem Tureci during an interview on BBC's "Sunday with Laura Kuenssberg."

A cure for cancer OR changing cancer patients' lives? That leaves open some possibilities. A treatment that knocks back a previously incurable cancer will "change cancer patients' lives." So will a treatment that doesn't cure it, but does control it to the point where it becomes a chronic disease. So will a treatment that greatly extends a patient's life after a disease becomes refractory, extending survival for years instead of months, which is often the case now.

So I remain skeptical of any treatment that claims to be a cure for cancer -- or skeptical of any headline that makes that claim. Especially a treatment that's essentially an idea. I'll be less skeptical when it's tested in a lab, and then in a phase 1 trial, and a phase 2 trial -- you understand what I mean.

But that doesn't mean I won't be keeping an eye on this. 

(It also means I fully expect to be around in 8 years to see if they were right. Expect a blog post either way. I have a good memory for these things.)

 

 

New (Expanded) CAR-T Trial

Early results from a new trial for a CAR-T treatment look very promising. It's not actually a new trial, but an expanded one. Still, the results are promising and worth keeping a close eye on.

The treatment is called MB-106, and is manufactured by a company called Mustang Bio. The company has already been conducting a phase 1/2 clinical trial at a single location, Fred Hutch Cancer Center. I wrote about this in May, when they reported results at the European Hematology Association meeting. 

This CAR-T treatment is different from those already available. It targets CD20, the same protein that is found on B Lymphocytes that is the target for many other B Cell Lymphoma treatments (like Rituxan). That is important because it means that patients who tried other CAR-T treatments, which target CD19, may be able to use this one as a next-line treatment. (That's one of the things the clinical trial is testing.)

The early trial of just 12 patients at Fred Hutch found that 11 patients had a response. There were 9 patients with Follicular Lymphoma, and 6 of them had a Complete Response. Side effects were great --  none of the patients had serious Cytokine Release Syndrome, and none had ICAN (a type of nerve damage that is common in CAR-T treatments). Four patients have had a Complete Response that lasted for more than 24 months, with the CR lasting 33 months (and still going, as far as I can tell).

The results were good enough to expand the trial. It is still a phase 1/2 trial, but now it will happen at 6 different cancer centers, and involve up to 287 patients. The patients will be put into 3 groups: one for patients with aggressive lymphoma (including transformed FL), one for patients with indolent or slow-growing lymphoma (including other types of FL), and one for patients with CLL. As a phase 1 trial, one of the goals is "dose escalation," or figuring out how much of the treatment to give a patient that will be most effective while creating the most manageable side effects. Once that is figured out, they will add more patients to each of the three groups.

The treatment is in the news this week because the company announced the early results from the first patient enrolled in the expanded trial. The patient did not experience cytokine release syndrome or ICANS, much like many of the patients from the earlier version of the trial.

It will be very interesting to see more results from this trial. Perhaps there will be more data presented in a couple of months at ASH, and definitely next spring at ASCO.

All of this is just more proof that CAR-T is going to be an important part of our treatment lives in the future. We're at the point where new CAR-Ts are not only going after different targets on cells, but are being developed so previous CAR-T patients can try a different version. That tells me that CAR-T is an established part of the treatment landscape for us.

Lots of questions still to be answered about CAR-T. Can someone develop an allogeneic or "off the shelf" version that will be as safe and effective, but won't require a specific treatment made for each individual patient? In the meantime, are there other ways to keep costs down? Can new developments figure out how to make CAR-T effective for that 20-30% that don't get a response at all? 

Stay tuned. I;m sure there be lots more CAR-T research to report in a couple of months as ASH approaches.

CAR-T Animation

The Peter MacCallum Cancer Centre in Melbourne, Australia (known as Peter Mac) has posted a very, very cool video. It shows how CAR-T works by showing the Killer T-Cells identifying abnormal (cancer) cells, connecting to them, and then signaling that the T cells should eliminate the cancer cell. It is extremely interesting.

The video, which won the "Best of Show" for both the Science and the Health categories at the Doctors Without Borders Film Festival, was created by  Dr. Maja Divjak from Peter Mac.

The video is about 11 minutes long, and it can be found embedded in a story on the Peter Mac website. The video is also available on YouTube, where it might be have more helpful tools for those of you who need translation help.

I really enjoy videos like this. For the most part, I can picture the kinds of processes that are involved with cancer treatments. And while I do my best to describe them in simple terms, a picture is certainly more helpful in allowing people to see what is happening. 

Maybe it's not really helpful in a lot of ways. Maybe seeing an immune cell find and eliminate a cancer cell doesn't help make the treatment any more effective. But to me, emotionally, it's great to see a treatment doing its job. It makes it seem more real. And for those of us with Follicular Lymphoma, a cancer with no easy answers and a lot of waiting around, seeing something that seems more concrete and real.

I hope you enjoy the video.

 

 

Secondary Cancers: A Reminder

In August, I wrote about secondary cancers in Follicular Lymphoma. It's worth bringing up again.

Last week, I had a growth removed from my forehead. The biopsy came back negative -- pre-cancerous. Not yet cancerous. But it could have been if I had let it go longer.

As I wrote in that post, Follicular Lymphoma patients are at higher risk for developing a secondary cancer -- a new cancer besides the FL. That's true for lots of reasons, including having "imperfect" immune systems due to our B-cell cancers, and sometimes because of treatments we receive, which can cause changes to our DNA that can get out of hand. It's good to be aware of that, and do all of the kinds of screenings that are recommended. I had a colonoscopy earlier in the year, ten years after my first one. The doc found a benign polyp -- no problem, but now I'll do the next one in 7 years, just to be sure.

And I see my dermatologist at least once a year, more often if I have a concern. My oncologist has been especially insistent about this, and I'm glad of it. I've had some weird skin patches removed over the last few years. The doctor says, "Oh that's a fliggamujangaping, nothing to worry about" as she freezes it off. I don't remember the names of the things. If she doesn't say "cancer," I pretty much stop listening and let her do her thing.

But this time, she came into the exam room and looked at my forehead and immediately said "I want a biopsy." The nurse prepared one as the doctor looked over the rest of my body, even the bottom of my feet, and said, "It all looks fine. Except that spot on your forehead. It could be squamous cell carcinoma. If it is, we caught it early. If it isn't, it's pre-cancerous, and we caught it before it became cancerous. Either way, don't worry about it."

And, strangely, I didn't worry. Maybe because I've already been through the shock of hearing "You have cancer" the first time, and it only shocks the first time. Or maybe the oncologist has been preparing me for this for a few years by telling me to get checked, so I kind of expect it every time. Or maybe I just took her at her word when she said "Don't worry." 

So this is your reminder to pay attention to potential secondary cancers. Being at higher risk doesn't mean we're guaranteed to get one. But it does mean we need to pay closer attention, and if we're concerned, to make sure we're listened to.

And if you're like me, and you can blame your Scottish/Irish/French Canadian ancestors for your fair skin and history of bad sunburns, then get your skin checked frequently. 

Take care of yourselves, everyone.