Sunday, June 30, 2019

Adding to the Maintenance Controversy

If you've been reading the blog for a long time, you probably know that there's a controversy in Follicular Lymphoma circles about Maintenance.

Maintenance is the idea that there is some benefit to continuing a treatment (usually Rituxan, but sometimes a different treatment) every couple of months for two years (though there are different schedules that are used), after the initial treatment (usually immunochemotherapy) has proven successful.

Every now and then, someone will publish research that shows the Maintenance is absolutely necessary. And then, a few months later, there will be new research that shows that there is no benefit, or that there might even be some harm.

Last November, I wrote about a presentation at ASH that showed there was no benefit to Maintenance, and it adds to treatment costs and could lead to Rituxan not working anymore for a patient.

Last July, I wrote about a study that showed there WAS a small improvement in Overall Survival and Progression-Free Survival in patients who had Maintenance.

A few months before that, I write about an earlier ASH presentation that showed that there was a PFS benefit, but no OS benefit, and once again questioned whether there potential Quality of Life issues make it worth it. A few days after that, I wrote a long piece, answering a reader's comment, about Maintenance and its long-term effects.

And that's only some of what I've written about Maintenance in the last 18 months or so.

My point is, it's definitely a controversial topic, and there hasn't been any research that has answered the question once and for all of whether or not Maintenance is a good idea.

And now we have another bit of research to add to the controversy.

At the International Conference on Malignant Lymphoma a few weeks ago, there was a presentation on the FOLL12 trial from Italy. The presentation was called "RESPONSE ORIENTED MAINTENANCE THERAPY IN ADVANCED FOLLICULAR LYMPHOMA. RESULTS OF THE INTERIM ANALYSIS OF THE FOLL12 TRIAL CONDUCTED BY THE FONDAZIONE ITALIANA LINFOMI."

(The original title was in ALL CAPS, and I decided to keep it that way here. My mom's father was born in Italy, and I lived there for 10 months when I was in school many years ago, and I like to imagine that the authors of the study just talk loudly and passionately about it, so the ALL CAPS just makes sense.

Actually, the lead researcher on the study, Dr. Massimo Federico from the University of Modena, discusses it in a video on Lymphoma Hub. He's very quiet and reasonable about it, not all loud and passionate. But I'm keeping the ALL CAPS anyway.)

The study looked at 800 Follicualr Lymphoma patients. Half were given immunochemotherapy, and then given Maintenance. The other half had immunochemo, but were then given "response-oriented therapy" -- they were given PET scans and then treatment was decided based on what was found. If the PET was clear, then no second treatment. Or they could have gotten maintenance, or some other treatment.

The researchers were expecting to find that response-oriented treatment would be the best choice. However, what they found was that the PET scans did not pick up all of the evidence that the disease was still there. So some patients didn't receive any second treatment or maintenance when they should have. Those patients had a PFS of 69%. But the patients who had Maintenance, whatever the PET scan said, had a PFS of 84%. Just getting maintenance as a matter of course seemed to help. They recommend that Maintenance be a regular part of treatment.

Interestingly, Dr. John Leonard, Lymphoma Rock Star from Weill Cornell, made this the #1 on his "leonard List" for the ICML conference. (He presented his list on Twitter, so I'm not going to link to it.) While he acknowledges the results of the study, he's not ready to accept Maintenance is the answer ("Findings undermine value of 'response adapted' rx in follicular NHL though value of maint R still debatable.")

So what does it all mean?

Well, for me, as someone who follows all of this stuff, it means I'm probably going to have some research to write about in a few months that says the exact opposite.

In all seriousness, I can't see any research coming down any time soon that shows that there is a definite benefit to Maintenance. It does seem to prolong Progression-Free Survival in a lot of patients, and that's a great thing. If a patient's goal is to have treatment and then extend it just a little bit with the idea that there won't be need for treatment for possibly many years, then Maintenance seems like a good idea. For others who are more concerned about other Quality of Life issues (Rituxan does cause some side effects, after all), then maybe no Maintenance is better.

No easy answers, I'm afraid. A conversation with your oncologist is your best course of action.

In the meantime, we can keep hoping for some research that DOES give us easy answers.

And be happy that we have a bunch of choices.


Sunday, June 23, 2019

Advancements in FL Treatment (Especially PI3K Inhibitors)

A little follow-up from my last post, which was about PI3K Inhibitors discussed at ASCO:

The American Journal of Managed Care did a special issue on PI3K Inhibitors in Follicular Lymphoma. Very timely.

There are four articles in the special issue. the first is called "Follicular Lymphoma: A Review of Mechanisms, Risk Factors, and Unmet Needs." It's a decent introduction to FL, though its purpose is to go through a lot of information. I think it needs to be read with a very careful eye. (It would be easy to misread this, for example, and think FL has two options -- either watching and waiting, or immunochemotherapy. there are, of course, lots of other options. It's a good intro for the doctors it was written for, but it doesn't present everything it could or should.

Skip it and go to the next article, "The PI3K Pathway: The Benefits of Dual Inhibition in Follicular Lymphoma." This one does a better job of laying out treatment options for FL, and where PI3K Inhibitors (Copanlisib and Duvelisib) fit into the picture. It's as good a summary of the research as you'll find.

The other two articles are interviews with FL experts. The first is "Advancements in Follicular Lymphoma Treatment: Where We Are and Where We Are Going. A Q&A With Andrew M. Evens, DO, MSc." Dr. Evans discusses current treatments for FL, especially PI3K Inhibitors. In some ways, it repeats what the previous article said, but in easier-to-understand language. It also gets into how one doctor would use them on actual patients. Dr. Evans also gives some thoughts on where FL research should go in the next few years. One area is paying more attention to Quality of Life -- and I am in total agreement.

Finally, there is "Evolving Population Health Strategies for an Expanding Treatment Spectrum A Q&A With Sheila M. Arquette, RPh." This article focuses on managed care, which is, of course, the whole focus on the journal it appears in. Managed care is a system of healthcare where a manager has some influence over treatment, making sure it is likely to work (statistically) and that the cost is worth the benefit. So while this article doesn't get into the treatment of FL the way Dr. Evans' interview did, it does provide a pretty fascinating look into how decisions are made by the people who have to pay for them. At its best, managed care reduces the cost of treatment while increasing its effectiveness. Patients don't always see the decisions in the same way. I'll leave it at that.

The special issue is definitely written for a particular group of readers, but it does give some additional insight into how FL gets looked at by people other than patients. That's pretty valuable.



Tuesday, June 18, 2019

ASCO: PI3K Inhibitors

More from ASCO.

PI3K Inhibitors have been an area of excitement in blood cancers for a few years. Like all inhibitors, PI3K inhibitors stop something from happening. Cancer cells go through a series of paths or steps to grow and live. Researchers have been able to identify what those paths are, and then how to interrupt or inhibit those paths.

PI3K stands for Phosphoinositide 3-kinase, which is a group of enzymes that are necessary for cancer cells to live and grow.

There are actually three PI3K inhibitors that have been approved (by the FDA) for Follicular Lymphoma.  Duvelisib was approved in 2018 for relapsed/refractory FL, and Copanlisib was approved about a year before that for relapsed FL. Idelalisib was approved in 2014 for relapsed FL.

There were a couple of nice presentations at ASCO this year that dealt with PI3K inhibitors.

One was about Copanlisib: "Long-Term Follow-Up of Patients (pts) with Relapsed or Refractory (R/R) Follicular Lymphoma (FL) Treated with Copanlisib." Interestingly, the reserach deals with both relapsed (a treatment worked for w while, then stopped working) and refractory (a treatment didn't work at all) patients.

This research looked at the patients who were in the trial that resulted in the FDA approval. 104 patents in the trial were given Copanlisib. In the current analysis, 59% had a response, with 20% having a Complete Response. The median for how long the response lasted was a little over a year. The CR numbers are higher than they were for the first analysis -- it was under 15% at that point. That included patients with "higher grade disease." Side effects were manageable, with no new long-term effects popping up after two additional years of study.


It's nice to see long-term results, even after approval.

Another presentation focused on a PI3K inhibitor called ME-401. This one is so new that it doesn't even have a cool name yet. The presentation gave the results of a phase 1b clinical trial. As part of the trial, 48 Follicular Lymphoma patients were given ME-401, by itself or with Rituxan. After a  median follow-up of about 9 months, 28 of the patients remained in the study. Responses were good, with 79% of patients of patients who had ME-401 getting a response, and 78% of patients getting the Rituxan combo getting a response. Patients were either given treatment every day, or for one out of four weeks. Those on the one week out of four had fewer side effects.

This is a very early study, with not many patients in it -- that's how stage 1 trials work. But they are good results, even if they're early, and we may see more of this treatment in the next couple of years, if they are able to move onto phase 2 trials.

It's all a nice reminder that, even if a first treatment doesn't work as well as we'd hoped, we have a lot of options for second and third treatments.


Thursday, June 13, 2019

ASCO: Patient-Reported Outcomes

More from ASCO.

"Patient-Reported Disease Burden in Chronic Lymphocytic Leukemia, Diffuse Large B-Cell Lymphoma, and Follicular Lymphoma: Results from a National Patient Advocacy Survey" focuses on PROs: Patient-Reported Outcomes. As the title shows, patients with three types of lymphoma were asked about the problems they had as a result of their disease.

As interesting as the actual survey results were, I think the fact that they are patient-reported is even more important.

The survey was sent to 424 lymphoma patients. 69 of them have Follicular Lymphoma. The patients were asked about the impact of their disease on their physical function, sleep, cognition (how well they could think and solve problems), work, emotional health, and quality of life (QoL).

The survey used what's called a "Likert Scale" -- patients are given a statement and asked if they strongly agree, agree, disagree, strongly disagree, or are neutral.

The results weren't all that surprising, especially this one -- most patients are worried about their disease coming back or getting worse (72% of patients with CLL, 83% of patients with DLBCL, and 79% of patients with FL). As the researchers point out, it doesn't matter if patients have a fast-growing disease like DLBCL, or a slow-growing one like CLL or FL -- most of us are worried about it. It's cancer. We're cancer patients. That's just the way it is.

As far as work goes, 31% of the overall group had their "employment status change." There isn't any more detail, but I assume that means they lost their job, or had to work less. This is also not a surprise. I was lucky that my own employment status didn't change, but I've heard from lots of FL patients who weren't so lucky.

Other results for Follicular Lymphoma patients:
68% agreed or strongly agreed that the disease had an effect on their energy levels.
52% agreed or strongly agreed that the disease had an effect on their sleep patterns.
65% agreed or strongly agreed that the disease had an overall negative impact on their Quality of Life.

I get a couple of things out of this.

First, survey results like this can tell us that we're not alone. One of the really great things about a support group is that you are likely to find someone else who has had the same experience, or has had the same feelings, as you. Having Follicular Lymphoma can be a lonely thing -- how many of us knew someone else with FL when we were diagnosed? (How many of us had even heard of it? Not me,  on both counts). Seeing survey results like this helps us know that we're not alone -- others are having the same problems we're having. There's a little bot of comfort in that, I think.

But more importantly, this research is another demonstration of the importance of Patient-Reported Outcomes. Any good doctor will ask about things like sleep, work, and energy, and help with any medical solutions. Good hospitals will have social workers or other resources to help with these issues, too. But those individual good things don't always get any farther than the doctor's office. A study like this gathers all of that in one place so many others can see the results. Researchers can base their own work on what patients are concerned about. Doctors who aren't asking those questions can be more aware that they need to.

And just as important, a study like this values patient voices. If we don't speak up, no one knows what we need.

So if you ever get the chance to talk about your experiences and give your opinion -- take that opportunity. It's good for all of us.




Conclusions: Pts with CLL, DLBCL, and FL report experiencing substantial disease burden. Data from studies focusing on pt-reported disease burden can be used for education of the clinical community to address the key concerns of pts.

Saturday, June 8, 2019

Oncologist Appointment

I had an oncologist appointment yesterday. Good news -- everything still looks good.

This was my second appointment with Dr. H, my fifth oncologist. Three of my oncologists have been generalists -- they deal with patients with many different kinds of cancer. Dr. H is my second oncologist who is a specialist -- blood cancers are his thing.

Dealing with a specialist means going to the research hospital nearby. Not a big deal; it's only about 20 minutes away from where I live.

But there are some downsides to going to the hospital for my appointments.

For instance, the hospital is full of sick people. That might sound funny-- of course the hospital is full of sick people. But when I went to my oncologist appointments at the satellite cancer centers, the other patients I usually saw were people who were like me, going for follow-up visits.

The patients at the hospital are sick. They wear masks. They look weak. The blood cancer ward is next to the children's cancer ward. There are kids in wheelchairs, walking with IVs, carried by their parents. Honestly, it brings back some bad memories.

And it makes me remember how lucky I am. My Follicular Lymphoma has taken an indolent course.  It has stayed slow-growing for 11+ years. My treatment with Rituxan was successful, and the short-and long-term side effects were manageable. I know that's not the case for everyone. I'm reminded of that every time I go to a hospital. And I'm glad I've been able to do small things to help those people.

Going to the hospital for my appointments also has another downside -- it's big and sort of impersonal, and there are hundreds of other patients there all the time. The staff is very nice. But there probably isn't much they can do to make the whole process easier. I had an appointment at 9:00am today. I arrived at 8:50. I finally saw the doctor at 10:20. I got bloodwork right after I saw him. I left the hospital at 11:00. That's 130 minutes at the hospital. I spent 110 of them waiting. Not fun.

When I did get to see Dr. H, everything was great. I know he presented at ASCO last weekend, and I had planned to ask him about the conference. But After all that waiting, I just wanted to go home. And I thought about those other cancer patients who have it rougher than me. No need to make them wait any longer than they already had been waiting.

It had been six months since I had seen him, so he looked over my file quickly. He was impressed with progress -- 6 rounds of Rituxan, 9 years ago. He said, "That's really instructive. I think we over-treat a lot of Follicular Lymphoma patients. We're thrilled if we give someone chemo and get 7 years before we need to treat again. But you're showing that maybe we don't need chemo. Maybe Rituxan will do the job. That's worth exploring more."

It's kind of cool to hear a researcher think through something like that. I don't know how representative I am of a pool of patients, but I'm all for less treatment if it isn't necessary.

He also said that, if and when I need treatment again, he'd probably just try Rituxan and see how it goes. (I'm open to all kinds of options. we'll deal with that when the time comes.)

We also talked a lot about good/bad food -- food that tastes good, but isn't necessarily good for you. Hot dogs, barbecue, ice cream, donuts -- we traded ideas for the best places to find them nearby. Certainly not something that should be eaten all the time, but I also see lots of patients online who try to be extremely struct about diet -- only certain vegetables, avoiding certain foods. There's no evidence that diet cures FL, or even slows it. Dr. H agreed that a hot dog or a glass of wine every now and then is good for your mental health, if it makes you feel good. Just don't overdo it.

After I was finished with the doctor, I went to separate part of the hospital to get my bloodwork done. A few hours later, the doctor's assistant called with the results: "Dr. H said it looked great. He never says 'great' about someone's blood work!"

I said, "Well, I told him I was a Super Patient. I'm glad he was listening."

So there it is. A good visit all around. I go back in 6 months for another visit.

I hope all of you are staying healthy, too. (And enjoying a little ice cream or a hot dog or a glass of wine, every now and then.)


Thursday, June 6, 2019

ASCO: PET Scans for Follicular Lymphoma

The ASCO conference was finished up last weekend, but I'm still getting around to looking at some of the research that was presented about Follicular Lymphoma.

Unfortunately, there wasn't really anything earth-shattering at ASCO about FL. In fact, I'm not really seeing any lymphoma news that's changing things in a huge way. And that's fine. Research is moving along at a really fast pace, but we can be patient and wait a little longer for some really great news.

That doesn't mean there wasn't some goof Follicular Lymphoma research that was presented at ASCO.

Another session that caught my eye was "Impact on Survival of Surveillance Imaging after First Remission in Follicular Lymphoma." In a way, this isn't presenting anything new. It was meant to confirm research that was done recently.

It caught my eye because I had a conversation with someone recently about this very topic -- the usefulness of PET scans after treatment.

The researchers in this study looked at an ASH presentation from a couple of years ago that found that PET scans do not help to detect a recurrence after treatment. That is, if you've had successful treatment, you're probably worried that the FL will come back. (Aren't we all?) Naturally, you think having frequent PET scans will help you keep an eye on this. A scan might pick up a small bit of cancer before it gets out of hand.

The problem, of course, with frequent PET scans is that they involve large amounts of radiation. Over time, that radiation can cause other problems, including new, different cancers.

And as that 2017 study found, the scans only pick up a very small number cancer recurrences that other things did find (a doctor's exam, or blood work, or even just the patient noticing symptoms). The ASH presentation that the research mention isn't online any more, but I did discuss it back then, if you want to take a look.

The ASCO research wanted to confirm what the 2017 study had found, and it did confirm it -- for most patients, frequent scans after successful treatment will not result in increased survival.

The research looked at 1121 Follicular Lymphoma patients who had been successfully treated and then had their cancer return. The patients' medical records were studied to see how the relapse was found -- either by clinical means (an exam by the doctor, or bloodwork, or patient noticing something strange), or by surveillance (a scan when no symptoms were present).

From that group, 117 patients had their cancer return. The median time for the relapse was 26 months. Of that group, 63 of them were detected by clinical means, and 50 by scans (4 were unknown). However, in that group, there was was difference in Survival between the two. Having the return of cancer found by PET scan did not mean the patient lived longer (but it did mean the patient had more radiation).

The researchers concluded that, for many patients, routine PET scans aren't necessary after successful treatment. If the cancer occurs, it is frequently found without the need for scans. They do acknowledge that there are some high-risk patients who might benefit from more frequent scans, and they would like to see more research that tries to identify those patients. But for most of us, frequent PETs probably aren't necessary.


Personally, I've moved toward believing that fewer PET scans for me are a good idea. I'm still young. I don't need the radiation unless it's necessary. I have an oncologist who feels the same way.

For you, the best thing to do is talk to your own oncologist. If you feel like the additionally radiation might be a problem, say so. Let your concerns be known. If you feel that your own mental health will benefit from getting a scan, say that too. Be open to being talked out of it, too -- maybe the doc can show you why your blood work and other exam information make it clear to her that a scan isn't necessary.

I plan to be around for a very long time. For me, understanding the long-term implications of everything I do really makes a difference.


Sunday, June 2, 2019

ASCO: CAR-T

First of all, a Happy Cancer Survivor's day to everyone!  The National Cancer Survivors day Foundation defines a survivor as anyone who has been diagnosed with cancer who is still alive today. It's a day worth celebrating. In fact, it's a reminder that every day is worth celebrating -- we should be sure to take some time, every now and then, to remember that.

I'm not going to spend too much time on Cancer Survivor's Day today (if you want to look back at what I had to say in the past, feel free -- it still holds true, especially the part about having a crush n figure skater Katarina Witt when I was a teenager).

More importantly, there are ASCO abstracts still waiting out there to be discussed.

My friend William asked me to check out what's being said about CAR-T. (William and Ben write a blog on CAR-T and Follicular Lymphoma. Ben had CAR-T, as did William's wife.)

There is a LOT of stuff on CAR-T at ASCO. It's an exciting treatment that shows a lot of promise. I've written about it before (a lot), but here's a reminder of how it works:

One of the body's defenses against invaders is a kind of white blood call called T cells. There are actually a bunch of different kinds of T cells, but there basic job is to figure out that there is an invader (like a bacteria or a virus) and attack it. T cells can multiply rapidly, so millions of them go on the attack.

But T cells don't work on cancer cells. Cancer isn't an invader from outside -- it's our own cells that have gone wrong. So CAR-T is a way of using T cells to go after cancer cells. Some T cells are removed from the body and changed in a way that lets them treat cancer cells as outside invaders. The new T cells can multiply and overwhelm the cancer just like they would any invader.

CAR-T is still in developmental stages (though it has been approved for aggressive transformed Follicular Lymphoma). Right now, about one third of patients have a long response to CAR-T, about one third have a response that lasts less than a year, and about one third do not have a response. My own oncologist thinks it will be much more effective in about 5 years. Another problem is that it is expensive -- it is basically a personalized cancer treatment, made just for each specific patient. It can also have some serious side effects, as the body is overwhelmed by the army of T cells, causing a reaction that could be fatal if not treated.

With so many presentations on CAR-T at ASCO, I won't get into too much detail about them, but here are some of the highlights:

  • One studied looked at Quality of Life in CAR-T versus Stem Cell Transplants. Unfortunately, aggressive treatments can result in severe side effects and lower QoL. The study found that CAR-T patients had the same QofL as the STC patients, and may have had fewer physical side effects in the month that followed treatment/
  • Another looked at Cytokine release syndrome, also known as CRS. That's the potentially deadly reaction that the body has when so many T cells kill off other cells at one time. the body has a reaction that's almost like getting a really bad flu. One presentation offered a way to detect CRS and deal with it before it becomes too harmful. (This has been a big area of research for the last few years, and it seems like doctors are able to watch for CRS and deal with it early.)
  • Another used PET scans as away to predict how effective a CAR-T treatment would be. By looking at a PET 30 days after CAR-T treatment, and comparing it to PETs taken after 90 days, researchers could figure out how to tell if the 30 day PETs could predict whether or not the CAR-T would be successful. early predictors like this are important; rather than waiting another 2 months to see if it worked, some patients can start a new treatment much sooner, saving valuable time.
  • Another looked at outcomes for DLBCL patients who had CAR-T. they found that patients who relapsed within 3 months of treatment had poor outcomes. But those who relapsed 3 months or longer after getting CAR-T did much better with the treatment that followed.
There weren't any presentations that looked at only Follicular Lymphoma and CAR-T. The clinical trial series that focuses on CAR-T and lymphoma is called ZUMA. So ZUMA-1 looked at DLBCL and Transformed FL, and the results of that trial were the reason CAR-T was approved. There are a bunch of trials (at least 8) that are looking at CAR-T and other blood cancers. One of them is looking at FL (not transformed FL, but just regular old FL). No results yet, at least not anything worth presenting at ASCO. Maybe at ASH in December, or ASCO next year.

I'm looking forward to seeing how CAR-T improves over the next few years. There is certainly a lot of research that's looking into making it happen.