CAR-T Approved for R/R Follicular Lymphoma

Big announcement yesterday for Follicular Lymphoma -- the FDA approved Tisagenlecleucel (also known as Kymriah), a type of CAR-T, for Follicular Lymphoma patients who are relapsed or refractory to treatment, and who have received at least two prior treatments. Earlier this month, the European Commission gave the same approval.

It's a big deal for FL patients, because it greatly increases the number of people eligible for the treatment, in the US and in Europe. Up until now, CAR-T treatments (there are several of them) were only approved for FL patients with transformed or more aggressive types of FL. It's still not approved as a first-line treatment, but that may come with time.

The announcement is very new, so there isn't a whole lot of commentary on it. I think that will happen in the next few weeks, especially as experts give their opinion during and after the ASCO conference. 

The approval came based on results from the phase 2 trial called ELARA. This involved fewer than 100 patients, and like all accelerated approvals, there will need to be a phase 3 trial with more patients to confirm that it is as effective and as safe as it seems to be. (This doesn't always result in permanent approval, as we saw recently with PI3K inhibitors.) 

The numbers, at least from what is being presented right now, look very good. One of the negatives about early CAR-T was that it was very effective for some, sort of effective for others, and not effective for the rest. I remember my oncologist kind of summing it up as, 1/3 of patients had a long-lasting response, 1/3 had a response that lasted a year, and 1/3 didn't respond. 

With multiple different version of CAR-T, there have been lots of opportunities for researchers to figure out how to improve the process, and the ELARA trial seems to show that they have been able to.  With a follow-up of 17 months, 86% of patients had a response, including 68% who had a Complete Response. Of those with a CR, 85% of them still had a response after 12 months. So that's an improvement over that one-third/one-third/one-third split. And it was effective even in patients who sometimes have trouble responding to treatment, like those with POD24 or who have had many treatments that stopped working. 

As for safety, the press release from the maker calls the results "remarkable." While 53% of patients in the trial had Cytokine Release Syndrome (CRS), none of them had a high-grade (more dangerous) type of reaction. Also, 43% of patients had nerve-related side effects, but only 6% had high-grade. The troubling safety statistic was that 3 patients died during the trial. This is one of those things that I would like to see more commentary on. I remember reading that some patients in early CAR-T trials had died from CRS, but that researchers quickly realized how to look for it and control it very early on. I don't know if that's what happened here, and the otherwise excellent safety statistics reflect that. I'll keep an eye out for more on what happened there. But if regulators in both Europe and the US have found the treatment to be safe, there has to be some explanation for those numbers.

Effectiveness and safety look good, so the next issue to consider is cost. CAR-T is still a fairly expensive treatment. But if it turns out that patients only need one very expensive that lasts a long time, instead of many moderately expensive treatments, that might make a difference.

As I said, I'll keep an eye out for more information and expert commentary about this, but for now, it certainly seems like CAR-T is going to be a part of more FL patients' lives from here on. I hope it proves to be as effective and safe for some of you as the trials would suggest.

 

Oncologist Appointment

Just got back from my 6 month appointment with the oncologist. Everything looks good.

This was kind of a strange appointment. Not the visit itself, but the build up to it. The appointment wasn't even on my calendar, so I only realized I had one a few days ago, when I got an email reminder. 

Then comes the really strange part -- last week, my wife and one of my kids got Covid. (Their symptoms have been mild to moderate, with no major health issues.)

I did not get it.

I tested three times, and was negative all three times, despite being very physically close to them, all of us living in the same house. It wasn't a surprise, really, that our family was hit by it. Numbers of Covid cases have been rising quickly where we live, though the numbers of hospitalizations have not risen so high. The Omicron variation seems much more easily spreadable, though less dangerous, especially to those who are double vaxxed and boosted, like my family. Or so say the experts, and they seem to be right.

Something similar happened in January, when another of my kids got Covid, and the rest of us tested negative. 

Both times, the rest of us tried to stay isolated, and wear masks when we had to be close to each other. That probably explains why I have still never tested positive for Covid. 

(Or there could be another explanation, like I'm super-human. But I'm not going to tempt fate and say something like that.)

Before the appointment with the oncologist, I tested negative with a home test, and called the doctor's office to explain the situation and make sure it was OK to come in. If there was even a little bit of concern from the doctor, I would cancel the appointment. The last thing I want to do is make someone else sick, especially another cancer patient. I spoke with an administrative assistant, and then with an oncology nurse, and then the office manager, and we decided that, since I didn't have any symptoms and I tested negative, it was OK for me to go to the appointment. Of course, I wore a mask, like everyone else in the hospital.

As usual, I had blood work done, and everything looks normal there. I had a physical exam, and the doctor didn't find any issues. And we talked, and I didn't bring up anything that concerned me. It was a nice, routine, undramatic visit -- just the kind that we like.

I usually ask the doctor about what excites him about lymphoma research lately, but I didn't get to that question this time. We mostly talked about Covid. He thanked me for calling beforehand and making sure it was safe for me to come in. We talked about what I should do if I do test positive -- call and talk about getting an anti-viral drug. We talked about if and when I should get another booster (probably in August, when there might be an updated formula for the booster, or more information about what a booster might need, and when I'm likely to be around lots of people again).

And we talked about how likely it is that Covid isn't going anywhere, and what that means. I don't like to think newer variations coming around being worse than what we've seen in the past. But I also am kind of used to trying to think three steps ahead of a disease, and having a plan in case I have a health issue and I need to respond quickly. That, to me, is the real value of staying educated. There's a balance between being prepared and not letting the fear of something dominate your life. But I've been doing that for 14 years. I'm kind of good at it at this point.

One final thought about the appointment. Everyone at the hospital seemed really kind and friendly today. I had to check in at the hospital entrance -- only patients and one caregiver are allowed in. The man who checked me in gave me my "screened" sticker, and then said, "I hope everything goes OK for you today." And he genuinely meant it -- looking me right in the eye when he said it.

When I got a blood draw, the phlebotomist couldn't have been better -- I barely felt the needle. I even said "Wow" out loud, I was so impressed. She jumped back. "I'm so sorry -- did I hurt you?" I laughed. "No, the complete opposite," I said. "I barely felt a thing. You were great." Just genuinely concerned.

The receptionist, the nurse, the scheduler -- everybody was great. There have been times when I have gone to that hospital and it all just seemed so cold. It was nice to have everyone seem to caring today.

I don't know what changed. Maybe tragedy has a way of changing how people do things, and those individual changes turn into a change for the whole institution. It was a nice reminder to step back every now and then and think about how small actions can make someone else's day just a little bit better.

I hope you all get good health news, too. Stay well. 

Access to CAR-T (and other treatments)

Two interesting and related items from the medical website Healio about CAR-T and race. I think that, together, they say important things about access to this important treatment.

The first is called "CAR-T for non-Hodgkin lymphoma effective regardless of race or ethnicity." It reports on research that looked at how well different CAR-T worked for patients of different ethnic groups and races. As the researcher in charge of the study points out, some treatments are less effective for patients of different races or ethnic groups. (He says this as a general statement, rather than giving specifics, which is too bad. I'd really like to know more about this.)

However, the study found that with CAR-T, these differences don't exist. The study looked at 46 patients, and divided them into two groups: Black and Hispanic in one group, and white and Asian in the other. (Again, the article doesn't give much detail as to why they were grouped this way.) The results showed that there were no significant differences between the two groups in terms of effectiveness or safety for CAR-T.

That's obviously excellent news. A treatment as promising as CAR-T, one that seems to be getting even better with time, is effective and safe for many who could use it.

The bad news, though, comes from another Healio article from a week ago. This one is called "Study finds ‘substantial’ underrepresentation of Black patients in CAR-T clinical trials."  The title should speak for itself. Despite up to 12% of CAR-T patients being Black, one clinical trial, as an example, with 88 patients had zero Black participants. 

That's bad for the very reason that the first study is good news -- if a treatment is less effective for some groups, that needs to be found out early. It's easy to assume that a small group of patients in a trial is representative of the entire population, and that's not always true. I think about the history of heart attacks in this way. For many, many years, the only research on heart attacks was conducted on men. It was assumed that whatever was found in the research would apply to women, too. Turns out women can have very different symptoms. Goodness knows how many thousands of women were not treated properly because it was assumed they were not having heart attacks.

So, in short, I have always been a big believer in clinical trials, and I always make sure to ask my oncologist about new trials, just in case I need to consider one in the future. Since I haven't needed treatment in 12 years, I haven't needed a trial. But they are so necessary in developing new treatments. I hope all of you will at least talk to your doctors about trials near you, and whether or not they are appropriate for you. Trial participants really are heroes.

And without wide representation -- by gender, race, ethnicity, age, socioeconomic status -- we can't truly know how well a treatment is. Not just by effectiveness and safety, but also by things like affordability and Quality of Life. Treatments aren't much good if they only help a small segment of people with a disease.

So there's my rant for the day. I've heard stories lately about people who weren't able to access treatment, or who weren't given a treatment that might have been more effective for them for different reasons. I want all of us to benefit from the great advances that have been happening in Follicular Lymphoma treatment, no matter who we are.

Stay well.

CAR-T for FL at EHA 2022

I know I don't write as much about Follicular Lymphoma news outside of the United States as I do about stuff in the USA. I know there is great stuff happening around the world. It's easier for me to get USA news, and I'm doing my best to find out about stuff happening elsewhere.

That's probably most clear around this time of year, as ASCO is coming up. (The same thing happens in December when ASH comes around.) Because I'm so focused on ASCO in May and June, I usually miss out on the European Hematology Association (EHA) Congress, which takes place a couple of weeks after ASCO.

As I said, I'm trying to be better about paying attention to other things. So I'm starting to see some announcements about research that will be presented at EHA this year. (Of course, they are from American companies, but that's who sends me press releases.)

One interesting piece of research is from Mustang Bio. At EHA, they will be presenting on their phase 1/2 clinical trial on MB-106, their CAR-T treatment. Unlike the CAR-T treatments currently available for FL, MB-106 targets CD20, the same protein that is targeted by Rituxan and many other FL treatments. The EHA presentation is called "IMMUNOTHERAPY USING A 3RD GENERATION CD20 TARGETED CAR T-CELL (MB-106) FOR TREATMENT OF B-CELL NON-HODGKIN LYMPHOMA (B-NHL) AND CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)." (It's in all CAPS because I had to cut and paste it because I'm too lazy to re-type it.)

It's a small study -- just 12 patients -- and is open to those who have had a different CAR-T (since they target CD19, a different protein.) Initially, 7 patients received the treatment, but it didn't work for any of them, so they made some changes to the process. After that, 11 of the 12 had a response. Follicular Lymphoma patients made up most of the cohort. There were 9 of them, and 8 of the 9 had a response, with 6 of them having a Complete Response. Safety was excellent -- none of the patients had serious Cytokine Release Syndrome and none had ICAN (a type of nerve damage). 

Looking forward to seeing more commentary about this. If these numbers hold up in larger trials, it will be a really nice alternative to other treatments available.

Another announcement I have seen is from Caribou Bioscience. (Mustang and Caribou? I assume your company needs an animal name to present at EHA?) Their presentation is called "FIRST-IN-HUMAN TRIAL OF CB-010, A CRISPR-EDITED ALLOGENEIC ANTI-CD19 CAR -T CELL THERAPY WITH A PD-1 KNOCK OUT, IN PATIENTS WITH RELAPSED OR REFRACTORY B CELL NON-HODGKIN LYMPHOMA (ANTLER STUDY)." This sounds like a fascinating treatment. It uses CRISPR technology. There needs to be a whole separate blog post about CRISPR, but it basically involves identifying which segment of a gene is responsible for a problem, cutting out that segment, and replacing it with a new "normal" segment. Very cutting-edge. It's also fascinating because it's an allogeneic CAR-T treatment. That means it doesn't use a patient's own T cells. It can use someone else's, possibly making it easier to create, and less expensive. 

This is also a phase 1 clinical trial. Only 6 patients, but 5 of 6 had a response (4 Complete and 1 partial). Safety was decent -- one patient had Cytokine Release Syndrome, and 3 had serious side effects (related to blood counts and nerve damage).

Both of these present some real possibilities for alternatives to CAR-T. It's already a very promising treatment, obviously, but that's how things work with cancer treatments. Researchers build on what works and they make it better. These are both phase 1 trials, and a lot can happen n the years before they are approved, but it's all exciting.

I'll keep looking for more interesting EHA abstracts, and I'll be posting some ASCO comments soon, too.

Very Low Dose Radiation for FL

Interesting research presented recently at the 47th Annual Oncology Nursing Congress. I haven't seen the actual research or an abstract, but Onc Live has a nice write up about it. The presentation had the excellent title of "Boom-Boom" Very Low Dose, 2 Fraction Radiation Therapy for the Treatment of Indolent Non-Hodgkin Lymphoma in the Palliative Setting."

How could I resist a presentation at a medical conference with a title that starts with "Boom-Boom"?

The "boom boom" actually refers to two doses of radiation given to patients with indolent NHL (that is, slow-growing lymphomas like Follicular Lymphoma). A reminder, for those who need it:

Some FL patients who have stage 1 or stage 2 disease can be treated (and maybe even cured, in some cases) with standard radiation. Unfortunately, only about 15 or 20% of FL patients are diagnosed with stage 1 or 2 disease. Symptoms just don't show up very clearly at that early stage, so most people are diagnosed accidentally, maybe when they having surgery for something else. Standard radiation works because the disease is located in one or two areas. That makes it easier for a beam of radiation to be aimed. It's a treatment that can work really well for some patients.

This research tested whether or not a very small amount of radiation can do the job -- just 2 doses, rather than the 12 doses that are typical. And the result is that yes, it seems to work for many patients. More importantly, when it doesn't work, another treatment can be started immediately, so the patient isn't put in too much danger. 

And just as importantly, Quality of Life is increased. If you've ever had radiation treatment or know someone who has, you know it's a grueling process, taking a long time and a lot of energy from the patient, with nasty side effects. Fewer doses means less of all of that.

What I find so interesting isn't so much the research results themselves, though it's great for the patients who will benefit from it. What's more interesting for me is that it fits into a pattern. A small pattern, but an important one -- more attention being paid to using as little treatment as possible to get the best results. It's an attitude that prioritizes patient safety and Quality of Life while still valuing effectiveness.

It matters to me because it's the approach that my first oncologist took. He recommended Rituxan, rather than something like R-CHOP, because he wanted to do as little harm as possible. And for me, it worked. 

Here, the research basically asks, "What is the least treatment we can give and still have the best outcome?" So if 12 works, how will 8 doses work? Or 4? or maybe 2?

It makes me think, too, about the controversy about PI3K inhibitors. The FDA is asking makers of those treatments to pay more attention to dosing -- to basically ask, "Can we give less of those treatment to patients, so we have similar effectiveness with fewer side effects?" 

I'm still waiting for abstracts for ASCO, which is happening in a few weeks, but I have been able to see titles. And one title that caught my eye suggests that lower doses of Rituxan, and just a little Rituxan maintenance, can be very effective with fewer side effects.

See the pattern? 

It's almost like the Lymphoma Community is saying "We have a bunch of things that work well. How can we make them work even better?"

I'll be looking for this pattern as I start to go through ASCO abstracts, to see if it's just these few instances, or if it's some bigger movement in the community. 

It certainly would an excellent thing, especially since many of us can expect multiple treatments during a long life.

 

Secondary Cancers in NHL (Some Good News for FL)

Really interesting article in the most recent issue of the journal Blood Advances. It's called "Incidence and time trends of second primary malignancies after non-Hodgkin lymphoma: a Swedish population-based study."It looks at a large group of NHL patients over many years, and how often they get a second cancer. There's some good news in there for Follicular Lymphoma patients.

The study looked at two large databases (over 30,000 people in each). One contained information about patients in Sweden who were diagnosed with Non-Hodgkin's Lymphoma (of many different types, including FL) between 1993 and 2014. The other database represented the general population. 

The purpose of the study was to compare how often NHL patients are diagnosed with a Secondary Primary Malignancy (or SPM), compared to how many people in general are diagnosed with cancer. In other words, they want to see if receiving treatment for NHL made you more likely to get another cancer later on. 

I want to stop here and emphasize something very important. This is a retrospective study -- one that looks backwards. It says a lot about people who were diagnosed with NHL between 8 and 29 years ago. It says less about people who were diagnosed more recently, for some very important reasons, which I'll get into below. This is very important to keep in mind as you read. I know many of us have a tendency to let our minds go to the worst possible outcome (myself included). Resist that, please.

To get right to the results: 

The study found that NHL patients diagnosed between 1993 and 2014 were about 42% more likely to get a solid tumor Secondary Primary Malignancy.  NHL patients over 70 years old had a higher rate of SPM than younger patients. The rate of SPM for one specific blood condition was about 5 times higher than the general population. That blood condition is Myelodysplastic Syndrome (MDS), which often leads to another blood cancer, Acute Myeloid Leukemia (AML). 

Remember, there's good news coming. Keep reading.

The results aren't really a surprise. We've known for a very long time that cancer treatment can cause secondary cancers. When I write about clinical trials, I often mention side effects -- things like lower blood counts, or nerve damage. Those are usually short-term side effects, which makes sense, because clinical trials only report side effects from a few years after the trial takes place. Secondary cancers are usually a longer-term side effect, and can show up years later -- if they happen at all. In this study, it was about 11% of patients that eventually developed a secondary cancer. And cancer is bad, obviously, but a 1 in 10 chance is much less worrisome than it might seem. And the MDS/AML was even smaller -- less than 1% of patients in the study.

So what's the good news?

Well, I see three pieces of good news from the article.

First, the rate of SPMs in the study held steady. In other words, the number of new cancers didn't get worse over time.

Second, while the rate of MDS/AML (the blood condition/blood cancer) increased overall for NHL, it actually DECREASED for Follicular Lymphoma. In the more recent years in the study, Follicular Lymphoma patients were about as likely as the general population to be diagnosed with this type of leukemia.

And that's the third bit of good news. The reason for this decrease, according to the researchers, is because Follicular Lymphoma patients are increasingly receiving non-chemotherapy treatments. From 1993 to 2014, the years of the study, that was most likely Rituxan. And even for those FL patients who received traditional chemo like CHOP or Bendamustine, it was often combined with Rituxan, which increased the time until another treatment was needed. Fewer treatments overall = fewer long-term side effects.

Think about that. As the researchers put it, there is an increasing number of non-chemotherpay options available for FL patients. For some of us with more aggressive versions of FL, immunochemotherapy (R-CHOP or B-R) is common. That's not a bad thing -- they work. For others of us, there are more non-chemo options available for first treatments. And for ALL of us, second and third treatments, when they are necessary, are increasingly likely to be non-chemo. 

It's chemo and radiation that are most likely to cause the kind of DNA damage that might lead to a secondary cancer. Years ago, FL patients would likely get chemo, and then follow it up with more chemo if necessary. That's just not the case now.

Think about the options available to us: Rituxan and Obinutuzumab, R-Squared, CAR-T, inhibitors. Bispecifics, soon. None of them are traditional chemotherapy. They will all cause side effects -- short- and long-term -- but it seems like the number of secondary cancers as a result of treatment are likely to go down. It will be really interesting to see a retrospective study 10 or 20 years from now, when those of us who have gone through treatment in the last few years, and in the few years to come, are studied for long-term side effects. 

Of course, this is a good time to remind everyone that I'm not a doctor or a cancer researcher. This is just me making an educated guess. But I'm also repeating what some very smart cancer researchers said, too, about FL. So I feel good saying it.

I was hesitant about writing about this, to be honest. I don't like to think (or write) about negative things like secondary cancers. But I like to write about hope, which is about good things that might happen in the future.

Hope won out with this one.

One final thing -- I'm guessing most of you are like me when it comes to cancer. We're constantly on the lookout for anything that doesn't seem right. The SPMs that were most common in this study were things like skin cancers and colo-rectal cancers. I probably don't need to tell you to do skin checks and get colonoscopies, but it's a good reminder. Prevent the cancers that you can, and catch them through early detection.

 In the meantime, stay well, and stay hopeful.