ASCO Follow-Up: Assessing Response in Follicular Lymphoma

The Journal of Clinical Pathways podcast this week featured Dr. Peter Martin, head of the Lymphoma Program at Weill Cornell Medical College in New York. He discusses a few sessions from the ASCO conference this summer, particularly the ones that focus on assessing response -- how we figure out whether a treatment worked.

You can listen to the brief (7 minutes or so) podcast, or read the transcript, by clicking here.

Dr. Martin first looks at the GALLIUM trial, and how researchers used PET scans to determine if the treatments they were studying (Rituxan + chemo vs. Obinutuzumab + chemo) worked. (I looked at this one, too. I always like when an expert thinks something was important that I thought was important Validates that sometimes I know what I think I know.) The PET scans helped doctors see if the patient had a complete metabolic response -- a much more detailed and accurate look at the treatment results than a CT scan. As Dr. Martin says, "As we're moving into an era where we're trying to predict who's likely to do well and who doesn't, it does appear that end‑of‑induction PET/CT scan may, in fact, do a fairly reasonable job of discriminating between those who are likely to do well and those who aren't."

Dr. Martin also addresses Bone Marrow Biopsies, a topic that lots of us are familiar with. (I hit on this topic, too.) BMBs are often required for clinical trials as a way of checking on how well a treatment worked. As he says, patients hate them, and doctors often discourage them, meaning patients don't go into clinical trials. So having a method that works well (like  PET scan) might help with clinical trial recruitment, too. 

And if we want new treatments, folks, we need clinical trials, and people to participate in them. Keep that in mind.

The last ASCO presentation he discusses was not one that I looked at. It examined PET scans in patients with Follicular Lymphoma grade 3b. Grade 3b is different from other types of FL, including 3a. It's often treated like an aggressive lymphoma, more like DLBCL than most FLs. PET scans helped identify bone marrow involvement, and could help identify a high-risk group of lymphoma patients.

So some nice commentary on the importance of PET scans in helping figure out how well a treatment has worked. There is some research that says a PET scan as a surveillance tool (using a scan in between treatments to see if treatment is needed) isn't always a good idea, but as a way of measuring treatment effectiveness, it can be very helpful.

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A quick word of sad news:

This week, we had to say goodbye to our dog Strudel. I only mention it because I know some of you have dogs, and Strudel actually made a few appearances in the blog over the years. She was almost 14. She was a good dog, despite the things I said about her.

She actually wrote a guest post a little more than a month after I started the blog.  Her sassiness came through even back then. It was a trait that stayed with her for her whole life.

I wrote about her when I wrote about cancer-sniffing dogs, too. Like the first dog trained to sniff cancer, Strudel was a standard schnauzer. However, she was not a cancer-sniffing dog, something that I resented (but I got over eventually).

I mentioned her again last summer, in a post about dogs and cancer. 

I'm going to resist the temptation to write more about her here, because I know I would go on for a very long time, telling stories.

Let's just leave it at this: she was a good dog with a lot of personality. There's a big hole in our house, and in our hearts, this week. 

Oncologist Appointment Today

I had my 6 month oncologist appointment today (a little more than 6 months since my last one, since the hospital messed up my last appointment). Everything looks good.

It didn't start well. It was probably the earliest appointment I've ever had -- blood draw at 7:30am and then seeing the Doc at 8:00am. I'm an early riser, so that was OK, but it meant I had to miss my morning 2 hour walk with my wife. Lots going on at work and home, too, so I was more distracted than usual.

I ended up going into the wrong parking garage (the one at the cancer hospital gives free or reduced parking to patients), and then when I realized my mistake, I went out the wrong exit, and it put me directly on an interstate freeway. So I had to drive to the next exit, turn around, and start all over again. 

Not a great way to start the day.

The hospital has strict policies about how to enter, so I went through that process to get in -- answering Covid questions, getting my temperature taken (by a machine, and not being able to line up my forehead correctly).  When I went a month ago, there was an army of people making sure only one person got into the elevator at a time, and giving directions for where to go. Not this time. They gave me a Visitor sticker and sent me on my way.

Now, where I live, Connecticut, was hit pretty hard by Covid in the spring, but people have been very good about wearing masks and keeping their distance, and we're now at one of the lowest Covid rates in the U.S. That helps a lot with my anxiety, knowing that there are fewer people around who have the virus and who might spread it. I'm still good about avoiding large crowds, and I always wear a mask around other people, but I'm still not much into big crowds these days.

So I was a little taken aback when I got off the elevator and walked into a crowd of people, all wearing scrubs. Apparently, 7:30am is the time the shifts change, so much of the hospital staff was either leaving work of arriving for work just as I stepped into the hall. It kind of threw me a little. It's the most people I've been around, by far, in the last six months. 

I went to blood draw first, and it was pretty uneventful. I am, and always will be, grateful for phlebotomists who do their job well.

The nice things about being in so early (other than the shift change issue) is that there are so few other people there. I'm guessing my 8:00am was the doc's first appointment of the day, so he has no excuse about being behind.

This morning, I was first seen by a Hematology Fellow, one of a small group of new doctors who have finished their degrees, finished their residency, and are now doing extra work in their chosen specialty. He was a nice young man, who asked me lots of questions and did a physical exam. Before he left to consult with Dr. H, my usual oncologist, I asked him why he chose Hematology/Oncology. He sat himself down (people like it when you ask them questions about themselves, and I genuinely like to hear people tell me their stories). He said he seriously considered being a General Practitioner, because he liked the idea of having a relationship with a patient for a long time. But he also knew that so many of the issues that a GP deals with don't really have solutions (people will live with high blood pressure, for example, for their whole lives). While he was in medical school, trying out different specialties, he found himself drawn to cancer patients. He thinks Hematology/Oncology will let him have long relationships with patients, but because there are so many new advances in blood cancer treatment, he'll also be able help fix their problems. He apologized for being "long-winded," but I told him it was really good answer. (And it says something that someone so new to the field thinks treatments are improving so much that he'll be able to help them.)

The Fellow left, and after a few minutes of consulting with Dr. H, they both returned, and I went through the whole thing again, answer questions and getting a physical exam, this time from Dr. H.

He said my blood work looks great. (I don't usually check myself, if the doc thinks it's OK, but so much of what we do now is through tele-health, so I'm on my "patient portal" more than I'd like to be. So I checked my numbers after the appointment, and I have to say, they look good.)

A couple of other interesting bits from our conversation:

He thinks a Covid vaccine will be available sometime in the spring. He also thinks that I should consider myself "medium priority." The people who should get the vaccine first are the elderly (I'm not there quite yet) and those who are in active cancer treatment, and thus have more compromised immune systems. Given how long it's been since I had treatment, my immune system has recovered somewhat from the Rituxan. This, however, is his (admittedly informed) opinion, and not set in stone. But it does give me a better sense of perhaps how I see myself in the middle of the pandemic -- not of the highest priority, but still taking it very seriously. 

He also mentioned possible treatments, if and when they become necessary. He thinks, right now, given the way my FL has stayed in check, he would probably recommend Rituxan again, or maybe Obinituzumab. He also mentioned CAR-T, and expects it to be approved for Relapsed and Refractory Follicular Lymphoma sometime next year. "We may be able to cure this thing," he said. (I told him "I'll believe it when I see it." I'm also optimistic about CAR-T's place, but I'm still not willing to say it's The Cure, at least not in its current version.)

I go back to see him in 7 months. 

A rough start to the day, but a good visit overall. 

I hope al of you are staying healthy, and having good days yourselves.

Lymphoma Awareness Month

 I'm a couple of days late, but September 15 was World Lymphoma Awareness Day.

(And September is Lymphoma Awareness Month, so I'm not late there. I think I'm still OK.)

Awareness day is sponsored by the Lymphoma Coalition, a group of 83 lymphoma-related organizations from 52 countries. The Coalition does a lot of work in gathering and sharing information about all kinds of lymphoma, and put out a report every year about Lymphoma-related trends. 

The theme of Awareness Day this year is "A World of Thanks," with the idea that we thanks those who help patients. Those include medical professionals, of course, like doctors and nurses, but also caregivers, friends, and lots of others who help in small ways.

I think I've mentioned this before, but not in a while: over the 12+ years since my diagnosis, I have discovered that there were people that I knew, but that I didn't know had impacted my life as a Follicular Lymphoma patient.

I remember dropping my kids off at school one morning, and chatting with the mom of a girl who was in the school band with my son. The mom was a doctor, and knew I had been diagnosed with cancer, but didn't know the details. I told her it was FL, and it turned out her husband was the head of the lab examined biopsies at the local hospital. "He's probably the one who diagnosed your cancer!" she said, with the kind of excitement that doctors have when they talk about doctor-y stuff. Didn't know that one.

A few years later, I was talking to an acquaintance about our health issues. We had volunteered to do some painting work at the kids' school one night, and a group of us were sharing a beer in the parking lot afterwards. I was giving some details about my treatment, and mentioned Rituxan. He got all excited. Turned out he worked in a facility that manufactured cancer treatments of all kinds. "Rituxan? I make that stuff up at work!" So someone I knew might have actually made my cancer treatment.

Soon after that, I was in the waiting room of the oncologist's office when my wife and I saw another school parent. She was excited to see us. It turned out she worked in the office, doing insurance claims, so we never saw her. But she just happened to come out into the waiting room that day. She probably helped make sure my treatment got paid for.

It's interesting that all three of them were "excited" when they found out about the connection. Not that they were all that thrilled to hear that I had cancer. But more that they had found out that they, in some small way, had helped me.

There are many, many people who help us (I hope) that we know about. Doctors and nurses and caregivers and friends. But there are so many other people that we don't even think about that play a role in our care. 

I'm not saying that we should feel guilty about not appreciating them. But it is kind of amazing to think that so many of us depend on so many others. And we, in turn, probably hep others in the things we do every day, without realizing it. 

On a day (or in a month) that emphasizes the worldwide scope of Lymphoma, it's important (for me anyway) to think about how connected we are. As different as we are, we have profound effects on one another's lives.

It feels like lots of folks could use a reminder about that these days.

Have a good rest of the month. Stay healthy and safe, and spread some awareness.

 

Expert Insight on Follicular Lymphoma (Video Series)

The website Healio has a new video series called "Expert Insight on Follicular Lymphoma."

The series features videos from Dr. Joshua Brody from Mount Sinai in New York City, and expert in blood cancers.

The videos are short -- under 3 minutes each -- and cover some very recent topics that are important to FL patients and the doctors who treat them. They include topics like recent clinical trials and approvals for FL treatments, advice for doctors who will give CAR-T to patients, significant unmet needs for FL patients. (Like many experts, Dr. Brody thinks one of the most significant unmet needs is finding ways to treat EFS24 patients -- those who relapse with 24 months of treatment).

It's an interesting series -- again, not really any new insights, but if you're looking for a good sense of where we are with Follicular Lymphoma treatments, it's a pretty good summary.

 

CAR-T for R/R Follicular Lymphoma

News from Friday: The makers of the CAR-T treatment Yescarta have applied for approval from the FDA for Relapsed and Refractory Indolent Lymphomas, including Follicular Lymphoma.

This is a big deal.

There's been a lot going on in the news in the last few months about CAR-T for R/R FL, so let's sort it all out.

There have been two CAR-T treatments approved by the FDA for aggressive lymphomas, including transformed FL. They are called Yescarta and Kymriah. 

While the approvals are for aggressive FL, they don't cover the kind of slower-growing FL that most of us are experiencing. But there are trials involving both Yescarta and Kymriah for R/R FL -- patients who have had treatment that either stopped working, or never worked at all.

A few weeks ago, the makers of Kymriah announced that their phase 2 for R/R FL trial was going very well. They didn't release any numbers, but promised to present them at upcoming conferences (probably the ASH conference in December). The FDA had already given them Regenerative Medicine Advanced Therapy Designation for R/R FL, meaning they were on rack to seek approval. But that hasn't happened yet.

Instead, Yescarta beat them to it. The phase 2 ZUMA-5 trial, which involves giving CAR-T to R/R FL patients, has really good results: a 95% Overall Response Rate, with a 81% Complete Response Rate. that's pretty great.

The usual caveats apply -- phase 2 is a small study (96 patients overall). The median PFS was just under 2 years. Those are both higher than the earlier trials that led to the first approval, which is very encouraging.

Then there's the cost of CAR-T. Since it's made specially for each patient, it can cost close to $500,000 per treatment. That's not a lot if it's the last treatment a patient needs, compared to how much all of the other treatments might cost.

And I have seen some FL patients online who have been very big fans of CAR-T, and who are saying this is going to be The Cure.

I'm thinking....maybe some day. But not yet. Researchers are learning more and more about how to make CAR-T treatments more effective and safer, and these results would back that up. But it's still too early to say for sure. 

In the meantime, we can be excited that another potential treatment is another step closer to being available for a larger number of people. I'm looking forward to hearing more about both types of CAR-T for R/R FL, and how realistic it might be for them to be available to lots of FL patients. 

Update: And remember, for more on CAR-T and Follicular Lymphoma, visit Ben and William's site CAR-T and Follicular Non-Hodgkin's Lymphoma.

Betalutin for Follicular Lymphoma: An Update

Updated results of a clinical trial on Betalutin, a RadioImmunoTherapy (RIT) treatment, were published yesterday in the journal Blood Advances: "Phase 1/2a study of ¹⁷⁷Lu-lilotomab satetraxetan in relapsed/refractory indolent non-Hodgkin lymphoma." The results look good, though the treatment has some complications to overcome. 

I have found RadioImmunoTherapy fascinating for a long time, probably because the RIT treatment Zevalin got an extended approval from the FDA around the time I started paying attention these things, in 2009. Around that time, I had met (online) a few Follicular Lymphoma patients who had benefited from it (and are still benefiting). 

RIT works by combining the best of radiation and targeted therapies. Regular radiation that is used on solid tumors just can't work on a blood cancer. The beam of radiation that goes after, say, a lung cancer tumor cannot hit a blood cancer cell. They just don't stop moving long enough to be hit by a beam of radiation.

To solve this problem, RIT takes a bit of radiation and attaches it to a monoclonal antibody (something like Rituxan). Because the antibody seeks out specific blood cancer cells (those that have the CD20 protein on their surface), the RIT antibody can bring that little bit of radiation directly to the blood cancer cell. It is less likely to affect healthy cells that way, while still giving the patient the benefits of radiation. 

Betalutin is a little bit different from Zevalin (or Bexxar, another RIT treatment for FL that is no longer available). The big difference is that Betalutin targets the CD37 protein, while Zevalin targeted CD20. 

The article gives updated results of a phase 1/phase 2 clinical trial. It involves 74 patients with Relapsed/Refractory indolent lymphomas, including 57 with Follicular Lymphoma. Patients were given Rituxan and Lilitomab (a monoclonal antibody that targets CD37), and then the Betalutin. (RIT is given in just one dose.)

Results were positive: The Overall Response Rate was 65%, with 30% Complete Response. For the FL patients, the ORR was 65%. For FL patients who had already received two or more treatments, the ORR was 70%, with a CR rate of 24%. The overall median duration of response was 13.6 months, and for those with a CR, 30 months.

Side effects were manageable, with the blood count issues that are common in lymphoma treatments.

Overall, pretty good results. Certainly not a potential cure, but, as the researchers point out, for R/R patients who need an effective treatment, but who may have physical issues that would make some more aggressive treatments too difficult. 

It's a fairly small study (naturally, since it's phase 1/phase 2), but there seems to be enough good news to justify a larger study. (And given the reports I see from the manufacturer of Betalutin, they seem pretty committed to going through trials and getting it approved.)

The potential problems for Betalutin (at least in the United States) don't come from the treatment itself, but from the regulations for how the treatment can be given. Only doctors with a specific type of training can administer the treatment, so unlike Rituxan or chemo, a regular old oncologist can't give this treatment. It has to be given by someone with special training, and it's not the kind of thing that most oncologists would go through. The reason for this is because the treatment involves radioactivity, which could be dangerous if not handed correctly. Lymphomation created a survey a few years ago asking the FDA to reconsider this regulation, though it doesn't seem to have had any effect.

As I said, I have been fascinated by RIT for almost as long as I have been a Follicular Lymphoma patient. I've spoken to some folks who had very good long-term results from RIT. It was only a few months ago that a very positive study of long-term effectiveness of Zevalin was published. search this blog for "Zevalin" or "RadioImmunoTherapy" and you'll see a lot of good stuff.

But it's a matter of getting that good stuff to the people who can benefit from it.

As I said, the makers of Betalutin seem pretty committed to getting this treatment approved. So maybe they'll do some of the work necessary to make it easier to administer, at least in the U.S. 

I look forward to more good results from future trials.