LRF Webinar on Follicular Lymphoma

The Lymphoma Research Foundation is holding another webinar this week that might be of interest to some of you. It's called "Update on Follicular Lymphoma," and it's happening this Thursday, June 27, from 3:00 to 4:00pm Eastern Time. 

As the webinar's name suggests, this session will provide information on the latest research on topics related to Follicular Lymphoma. In particular, it will cover:

• Overview of Follicular Lymphoma (FL)
• Active Surveillance (Watch and Wait)
• Treatment Options for Newly Diagnosed Patients
• Treatment Options for Relapsed/Refractory Patients
• Emerging Treatment Options

So as you can see, no matter where you are with your FL, there is likely to be something useful for you. 

I don't think they will be presenting anything brand new, the way they would at a medical conference. But it will probably provide the kind of 'big picture" that I always enjoy reading and watching -- here's the latest on Follicular Lymphoma. I think that kind of overview is really valuable, especially for newly diagnosed folks. Sometimes we're so focused on our own piece of the puzzle that we don't get a chance to step back and see the whole thing. 

It's scheduled to last an hour, so I don't know how much depth they'll be able to go into, but it's still probably a great overview.

Speaking of "they" -- the presenters will be Dr. Philipe Armand, who is in charge of Lymphoma research at Dana-Farber in Boston, and Dr. Carla Casulo from the University of Rochester, where she is a professor ar their medical school. I don't know as much about Dr. Armand, but I have definitely heard Dr Casulo speak, and she's great. It should be an excellent webinar.

You can register online here. I hope you'll consider taking a look.

 

EHA: Treatment Preferences for Patients with R/R FL

I've said this before -- I know that many of you live outside the United States, and I try to make an effort to look at research from outside my country, or research that affects those of you in other countries. I know I could do better with that.

So I'm going to look at some of the research from the European Haematalogical Association meeting from last week. It's the European equivalent of ASH, and their meeting happens immediately after the ASCO meeting in the U.S. (which is why I probably don't talk about it much). With so little FL news at ASCO, I was hoping that there would be more at EHA, and indeed there was. 

I'll start with a presentation called "Treatment Preferences and Quality of Life in Patients with Relapsed/Refractory Follicular Lymphoma." 

The researchers acknowledge that first, most FL patients will end up needing more than one rund of treatment -- we will likely be relapsed (our treatment stopped working) or refractory (the treatment didn't work in the first place). And second, with more treatment choices than in the past, the needs and preferences of patients are becoming more important.

So they set out to find what those needs and preferences were. They surveyed 195 R/R FL patients in the U.S., Germany, the U.K., Brazil, France, and Japan. They were interested in Quality of Life, which they measured with several particular surveys. They found that their disease and its treatment had indeed affected their Quality of Life. For example, among the 62% of the patients who currently held jobs, in the 7 days before the surveys were filed out, 35% had missed work, 38% dealt with presenteeism (being at work, but not being as productive), 49% felt overall work productivity impairment, and 42% felt overall activity impairment.

This is no surprise. Whether from the disease or from the short- and long-term side effects of treatment, we're often not ourselves. And any 7 day period will have different numbers (we all have our good days and bad days), but it seems pretty accurate to say that about half of us just don't feel like our full selves at any given time.

What I found even more interesting, though, were the questions they asked about treatment choices. They asked the FL patients which of the following factors played a role in deciding which treatment to go with -- Progression Free Survival (PFS), 5 Year Overall Survival (OS), Serious Adverse Events (side effects), Cytokine Release Syndrome (CRS), Neurological Events (NE), Fatigue, and Administration (the time and effort it takes to receive the treatment). They did this by giving the patients pairs of factors ("Which is more important, PFS or Fatigue?) until each patient had chosen each factor in relation to each other treatment factor.

What I found so interesting is that the things that mattered actually changed with each round of treatment. 

For patients who were receiving their second treatment (remember, these are R/R patients), the most important factor was PFS -- having as long a stretch as possible before the disease came back. Second most important as reducing the risk of NEs. That says as much about their first treatment as it does anything else -- nerve-related issues must have been very common in their treatment. (The abstracxt doesn't say what their first line of treatment was.) And PFS just makes sense -- they've been through treatment already, and they don't want to get the news for a third time that they have active FL. 

And for these patients receiving a second treatment, 5 Year Overall Survival and reducing Serous Side Effects were least important. The 5 Year OS makes sense to me -- there seems to be a kind of acceptance that this is probably coming back, and PFS matters more than OS (they both measure Survival). The risk of Serious Side Effects is a little surprising, though. But it does add to the idea that these patients just want to stay alive and are willing to risk the problems that come with that.

Interestingly, patients who had received a third treatment ranked Administration as most important. The researchers think that having Autologous Stem Cell Transplants was an influence here; an Auto SCT involves getting treatment, removing healthy immune cells, getting more treatment, and putting the cells back in, and waiting for the immune system to rebuild itself. It's a long process, and much more involved than most other treatments. The third treatment group also valued increasing PFS. Least important were, again, Serious Side Effects and Cytokine Release Syndrome (a potentially serious side effect in its own right).

Certainly, each of us will have our own priorities when it comes to treatment, and no doubt some of these factors will play a role. As you probably know, I have been very fortunate to have an indolent disease so far, and so I haven't had need for a second round of treatment. I do talk about that choice often with my oncologist, and I suppose when I make that choice, it will depend on how aggressive the disease presents itself. 

But the big take away for me is that it is worth thinking about, even when we don't need it yet. I'd rather have the time to think through those decisions now, rather than making them when I'm probably going to be more emotional than I'd wish. 

And most importantly, it's great that oncologists are recognizing that more treatment choices means more decisions for patients -- and the good and bad that having so many choices can bring.

T Cell Lymphoma After CAR-T

I may get back to a couple more ASCO presentations, but for now I want to write about three articles in the New England Journal of Medicine this week. You probably remember that in January, the FDA issued a warning about CAR-T. There seemed to be an increased risk of developing secondary cancers, especially T Cell Lymphoma, after CAR-T. Some research a few months later looked at how common those T Cell Lymphomas were.

Now the NEJM has published more research on this topic. Two studies looked at groups of CAR-T patients who developed T Cell Lymphoma after treatment. The researchers in both studies were especially interested in where the secondary T Cell Lymphomas came from. There had still been some uncertainty about whether the new cancers came from the manipulated T Cells. (Remember that CAR-T involves removing T Cells, a kind of immune cell, from the patient; then changing the cells so they can recognize cancer cells; then putting them back into the patient.) The concern is that changing the T Cells makes them more likely to become cancerous themselves.

I'll give you the bottom line -- it's possible that the treatment can lead to the secondary cancer.

One of the studies, "Risk of Second Tumors and T-Cell Lymphoma after CAR T-Cell Therapy," looked at 724 patients who had received CAR-T at their center. Only one of them developed T Cell cancer -- a patient with Diffuse Large B Cell Lymphoma. The researchers performed a number of tests on samples of the two lymphomas, and found that they were genetically unrelated. However, both were positive for Epstein-Barr Virus, a very common virus that does have a connection to some cancers, including Burkeit's Lymphoma and Hodgkin's Lymphoma. The study isn't suggesting that DLBCL is caused by Epstein-Barr, but there may be some issue that ultimately leads to cancer forming -- in this case, independently of one another. In other words, the T Cell Lymphoma might have come about from the same general conditions as the B Cell Lymphoma, but they are genetically unrelated to one another.

In the other study, "Indolent CD4+ CAR T-Cell Lymphoma after Cilta-cel CAR T-Cell Therapy," researchers looked at a different group of patients who were given a different type of CAR-T. This study looked at a single patient who had received CAR-T as a treatment for Multiple Myeloma, a different type of blood cancer. In this case, the researchers did find a genetic connection between the new T Cell Lymphoma and the T Cells that had been changed as part of the treatment. The researchers looked deeply at the samples and seem to have found the genetic alternations that resulted in the T Cell turning cancerous.

To be clear, these two studies weren't comparing the same samples or the same patients -- or even the same CAR-T treatments. And while I say it is possible, I mean that they aren't coming right out and saying CAR-T will definitely lead to cancer, because that's just not true.There have been thousands of patients who received CAR-T who have not had any issues with secondary cancers. They're saying there's a possibility -- but they still don't know why or how.

That's why the third article that issue of NEJM, "T-Cell Cancer after CAR T-Cell Therapy," tries to bring together what the two studies say and add it to what we already know. They point out that there is a connection between the treatment and the new cancer in that second study, but still don't know how it arises. That single case of T Cell Lymphoma came from a pool of 587 B Cell Lymphoma patients, making the rate of incidence 0.17%. That's in line with the data that the FDA reviewed, which identified 354 cases of T-cell lymphoma in 288,478 patients with B-cell lymphoma, an incidence rate of 0.12%.

The important part of these studies is their attempt to identify whether or not the treatment causes the secondary cancer. Patients (like us) with B Cell Lymphomas are about 5 times more likely than the general population to develop a T Cell Lymphoma, meaning the conditions for someone receiving CAR-T are already greater.

In the end, I can't imagine that this research will cause the FDA to change its recommendation about CAR-T. The Black Box Warning will remain, and patients will still need to have that conversation with their oncologists. But the FDA will likely conclude that the benefits of CAR-T far outweigh the risks.

ASCO: Epcoritamab and Safety

As I have said before, this year's ASCO meeting was short on Follicular Lymphoma presentations. One of the big focuses for FL was on bispecifics, and Epcoritamab made its presence known.

Epcoritamab is a bispecific, attaching to CD20 on the cancer cell and CD3 on the T cell. (You can read more about bispecifics in my last post.) It was approved for Diffuse Large B Cell Lymphoma (including DLBCL that arose from transformed Follicular Lymphoma. In February, it was granted accelerated review for Relapsed/Refractory Follicular Lymphoma. A decision is expected within a  few weeks.

So it's no surprise that it got lots of attention at ASCO this year. My guess is that it will be approved. I have absolutely no insider knowledge about this. Just in my observation, the makers of treatments tend to keep quiet if they are expecting bad news, and Epcoritamab isn't being quiet.

In one ASCO presentation, researchers focused on safety. Because Epcoritamab is already approved in the U.S. and Europe, there is a good deal of data on its side effects. Like other bispecifics (and like CAR-T), Cytokine Release Syndrome (CRS) is a concern. (As a reminder --  CRS happens when the body releases too many immune cells all at once. With treatments like bispecifics and CAR-T, the whole point is to get the immune system to go after the cancer cells. But when that happens, the immune cells doing their work will signal to other immune cells to come and help. Those signals are sent through cytokines, and a fast build up on cytokines results in fever, low pressure, breathing trouble, and other dangerous issues.) In the ASCO presentation "EPCORE NHL‑1 follicular lymphoma (FL) cycle (C) 1 optimization (OPT) cohort: Expanding the clinical utility of epcoritamab in relapsed or refractory (R/R) FL," researchers looked specifically at patients who at potential issues with CRS and tried to find ways to identify the problem early.  Patients were hydrated and given dexamethasone, and anti-inflammatory drug, and were able to avoid hospitalization. Similar studies seem common in CAR-T as well. There is an increased understanding of how common CRS is and how important it is to treat it as soon as possible.

In another presentation focused on safety, "Subcutaneous epcoritamab (SC epcor) administered outpatient (outpt) for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL): Results from phase 2 EPCORE NHL-6," patients were given subcutaneous Epcoritamab (by an injection rather than by an IV) and monitored for side effects. The results were similar to the other presentation, in that there was some CRS, but it was carefully monitored and treated, and there were no hospitalizations required. 

The two presentations are obviously related, but they are looking at different forms of the treatment. An IV has potentially different side effects than an injection (subcutaneous Rituxan had to go through a whole different process to be approved by the FDA, 20 years after Rituxan was first approved). An IV can be slowed down, as it often is with Rituxan, because of allergic reactions (that happened with me when I received it), whereas an injection gets all of it to you at once. But these two studies show that Epcoritamab can be administered safely no matter the form. Again, there just seems to be an increased awareness of the likely side effects that come with stimulating the immune system to intensely. 

And I'm sure the FDA has safety in mind as they finish reviewing the application for R/R Follicular Lymphoma. It's always a concern, of course, but even more so lately, it seems, as newer types of treatments are approved and new safety concerns arise. 

I'm guessing that I will have news about Epcoritamab's approval very soon. Stay tuned.

ASCO: Bispecifics for Follicular Lymphoma

As I have said, there isn't too much new and exciting related to Follicular Lymphoma at ASCO this year. One big theme, though -- Lymphoma experts are still very excited about bispecific antibodies.

In case you need a reminder, bispecifics work a lot like the monoclonal antibodies that have been around for almost 30 years. A monoclonal antibody (like Rituxan) works by attaching itself to a protein on the cancer cell (Rituxan attaches to the CD20 protein, like many bispecifics). What makes a bispecific different is that it also attaches to a protein (like CD3) on a T cell, a kind of immune cell. By bringing the cancer cell next to the immune cell, the bispecific uses the body's own immune system to treat the cancer.

Trials treating FL with bispecifics have been very successful, with one already approved and a number of  others at different stages of the trial and approval process. (Search for bispecifics in this blog and you'll see what I mean.)

A large percentage of the FL presentations at ASCO are about bispecifics. It's one of the two treatment types (along with CAR-T) that get talked about most by lymphoma experts these days.

So I was excited to see that there was a session on Bispecifics at ASCO -- not presenting trial results, but an hour-long discussion with a panel of experts. It's called "Innovative Strategies: Bispecific Antibodies for Relapsed/Refractory Follicular Lymphoma," and you can watch it on YouTube with the link in the title.

It's worth the hour it takes to watch it. You'll get a good sense of the state of the art with bispecifics. I will caution, though, that in this video, the cameras stay on the three doctors. They keep referring to slides with data and information, but they don't show them in this recording. But that's OK -- you miss out on some specifics, but you get the sense of what's happening. They're excited -- that much is obvious.

I won't summarize the entire hour discussion, but I do want to share some important highlights. 

The three presnters are Dr. Gilles Salles of Sloan Kettering in New York, Dr. Joshua Brody of Mount Sinai in New York, and Dr. Matt Lunning of the University of Nebraska.

Before they got into their individual presentations, they did some polling of the oncologists in the audience. They first asked them what their experience is with bispecifics. Again, I can't see the actual results, but they do discuss them. About half of the oncologists there had no experience at all with bispecifics. Another big chunk had only used them once or twice.The conference is a mix of researchers and clinical oncologists (the folks you see in their offices), so this makes sense. Bispecifics are pretty new, and the one approval is for Relapsed/Refractory FL, so that narrows the number of patients who even have the chance to see them. 

But it also makes the point that I need to hear. As much as I read about bispecifics when I do research on FL, a lot of that is in the lab, not the clinic. In other words, what we're seeing at ASCO, with most FL presentations being about bispecifics, that doesn't mean they are showing up in the oncologists offices.

That said, one of the panelists also warned the clinical oncologists in the audience to learn all that they could, because bispecifics are going to be an important part of treatment plans for FL in the very near future.

Along those same lines -- another poll asked the audience members how many bispecifics had actually been approved. We know the answer is just one (so far) but a lot of the audience got it wrong and thought there were more that have been approved. That's understandable -- many oncologists are generalists that treat many different kinds of cancer. But it again reinforces the idea that bispecifics are probbaly talked about and written about more than they are actually used at this point.

A lot of the discussion from here was providing some important clinical information and advice, particularly related to side effects and how to identify and treat them before they become problematic. CRS (Cytokine Release Syndrome) is an issue for bispecifics, and the panel offered advice on how to deal with it. (And they make the point that it is less common to have serious CRS with bispecifics than with CAR-T, but it's still important to keep an eye on it.)

As for the future of bispecifics, as I said, they warn the members of the audience to learn what they can, because they are likely to become a more important part of treatment regiments very soon. The panelists were asked what kind of advice they would give to clinical oncologists about using bispecifics. One pointed out how important it is to follow dosing instructions to prevent CRS. The other suggested they keep in touch with researchers who have used bispecifics a lot in clinical trials, and who continue to use them, because we are learning more and more about them all of the time. Once again, these answers point to how little experience most oncologists have with them. 

In another response, one of the panelists said that it was very possible that bispecifics would be used the way Rituxan is used now. It is used and it works, and then perhaps the FL returns, so bispecifics are used again, and again if necessary, until they stop working. That says a lot about how these experts think about bispecifics effectiveness but also their safety. 

As I said there is much more here. I've tried to share what I think are the highlights. 

I think the takeaways here are 1) lymphoma experts continue to be excited about bispecifics; 2) data continues to come in that justifies that excitement; 3) it's pretty likely that your oncologist hasn't used bispecifics, especially if you are not seeing one in a research hospital; and 4) it's pretty likely that bispecifics are going to be a part of many FL patients' treatment plan at some point in the future, as a first line treatment and for R/R patients.

I'll keep digging into the FL information that's being presented at the conference and report what I find out. Not as rich a mine to explore as in the past, but some good nuggets in there.