Princess Catherine and Survivorship

Catherine, Princess of Wales, spoke a few days ago about her post-cancer life. It happened as she was visiting patients at a hospital. It seems like it was prompted by her dropping out of an event (the Royal Ascot, a horse racing event) that the Royal Family traditionally attends each year.

In the interview, she talked about the struggles she has had since finishing her cancer treatment. It is remarkable in the way she covers most of the issues that are related to survivorship.

I won't go through everything she said, but it amounts to this:

After successful treatment, everyone, including yourself, can think that everything is OK.  During treatment, she said, "you put on a sort of brave face." But when treatment is over, it can be "really difficult."

Part of the difficulty is physical -- your body is still recovering from the side effects of treatment. As she said, "You're not able to function normally at home as you perhaps once used to."

And part of the change is psychological. After treatment is over, "then it's like 'I can crack on, get back to normal'." But "the phase afterwards is really difficult, you're not necessarily under the clinical team any longer."And without that team that you were working with, there's some element of fear that comes with it. All of this lines up pretty much exactly with the recent survey results that I wrote about a few weeks ago.

One of the patients she talked with agreed: "It can be very discombobulating, in that time when you've finished active treatment."

I think all of this is a great reminder that survivorship isn't easy. As she said, "It's life-changing for anyone, through first diagnosis or post treatment and things like that, it is a life-changing experience both for the patient but also for the families as well....You have to find your new normal and that takes time... and it's a rollercoaster it's not one smooth plane, which you expect it to be. But the reality is it's not, you go through hard times."

And in a weird way, that should be comforting. If you're post-treatment and struggling, whether it's physical or emotional or spiritual -- you're not alone. I'm sure Catherine is getting the best treatment and post-treatment care possible, and she's struggling anyway. Cancer doesn't much care whether or not you have a crown on your head.

The lesson, of course, is to seek help if you feel like you need it. See if your cancer center has a survivorship program. If not, ask your oncologist of there are services available -- physical therapy, or a social worker or other mental health counselor, or a nutritionist, or something else (the Princess apparently found acupuncture very helpful).   

I appreciate Princess Catherine being willing to speak out about this. I remember when her diagnosis was first announced, there was little detail given, and I defended her right to keep things private. We all need to deal with our diagnosis and treatment in whatever way makes most sense to us and helps us. I would love it if every famous person was completely open about everything. But that's not their responsibility. They owe no one anything, except themselves and their loved ones.

So Catherine speaking out about survivorship is a wonderful thing. I hope it brings some comfort to a lot of patients and survivors.

Primary Extranodal Follicular Lymphoma

The journal Hematological Oncology just published an article called "Primary Extranodal Follicular Lymphoma: A Retrospective Survey of the International Extranodal Lymphoma Study Group (IELSG)." It actually doesn't affect most of us directly, but I think the bigger picture is probably important to us all.

The study described in the article looks at Primary Extranodal Follicular Lymphoma.

Extranodal FL means FL that exists outside the lymph nodes, and other organs related to the lymphatic system like the spleen and bone marrow. It's fairly common for FL to move out of the lymph nodes and into the spleen or bone marrow -- that's the very definition of stage 4 for FL, and about a quarter of FL patients are diagnosed with that stage. 

And if the lymphoma starts in the lymph nodes and then moves somewhere else, it's called secondary extranodal FL.

This article looks at primary extranodal FL -- it starts in some part of the body other than the lymph nodes.  

As I said, this doesn't apply to most of us, but I have communicated with a few readers over the last couple of years who have had their FL present in this way. Maybe some of you are still reading.

The research was conducted by the International Extranodal Lymphoma Study Group (IELSG), made up of Lymphoma experts who are specialists in these types of Lymphomas. Keep in mind that "Lymphoma" is a very broad term, and there are as many as 90 different types of Lymphoma, depending on who is doing the counting. About 30 of them are Extranodal types.

This research looked specifically at Primary Extranodal Follicular Lymphoma. This seems much less common than other types of Extranodal Lymphomas. I say "seems" because, as the authors note, extranodal FL "has not been extensively described." So they set out to find as much as they could by surveying specialists about cases that they had documented. They looked at "605 pathologically reviewed cases from 19 different countries" so they could compare the clinical features at diagnosis and their outcomes, and compare them to nodal FL.

What they found was that the two most common sites for Extranodal FL were the skin (334 of the 605 they looked at) and the gastrointestinal tract (72 of 605). More importantly, those two subsets were very different from nodal FL and had different Overall Survival patterns. After a median follow-up of 5.5 years, the cutaneous (skin) FL had an 89% 10 year OS, and the gastrointestinal FL had a median 10 year OS of 79%. For those gastrointestinal FL that presented in the duodenum (the first part of the small intestine), the OS was 95%. Other extranodal FL sites were similar to nodal FL. 

I think this is all good news for those of you with Primary Extranodal FL.

The bigger picture, though, is what interests me more. The researchers conclude by saying "These findings support the identification of specific primary FL localizations as distinct entities with particular clinical and biological characteristics." In other words, not all FLs are the same.

In some ways, that's really obvious. FL has a reputation for being heterogeneous -- it seems like we're all a little bit different. That was the conclusion of one of the ASCO presentations that I reviewed a couple of weeks ago. 

And yet, as obvious as it seems, we're still all kind of lumped in together as "Patients with Follicular Lymphoma." I think this goes back to not so many years ago, when diagnosis was done mostly by microscope. On the surface, all FL cells look very alike. As diagnostic tools, and our understanding of genetic features, becomes more sophisticated, it gets easier to see the differences. So some of us are probably still close enough to be a patient with FL, and to follow the same treatment recommendations as everyone else.

But that greater recognition that not every FL is the same will have significant implications in the future. We already know that, for example, grade 3B FL isn't really like other FLs. And POD24 FLs aren't really the same as others. But the more researchers can recognize specific features of different subtypes, the better off we will all be when it comes to diagnosis and treatment.

So that's my takeaway from all of this. It seems like very positive news for those of you for with Primary Extranodal FL. And for all of us, it's at least a small step toward making FL a little more manageable by identifying the things that make it heterogeneous. 

And those small steps are what move us forward.

 

Survivorship and Lymphoma

I've written a lot lately about the idea of "survivorship" -- what happens after treatment is over. It's an important issue for al cancer patients. Very often, health professionals are focused on making us better, and there isn't time or resources or expertise to deal with what happens after that. 

That's changing somewhat, and more and more cancer centers are focusing on survivorship, sometimes by having a dedicated office or clinic for patients who are no longer "patients," but who are still dealing with the physical and emotional effects of cancer, months or years later. That's certainly not the case for every cancer center, though.

I bring this up again because JCO Oncology Practice recently published an editorial on the topic, specifically on survivorship for Lymphoma patients.

I'll get to that, but first I want to look at the article that the editorial was responding to. It was aso published in JCOOP, in February. It's called "Perspectives of Lymphoma Survivors and Oncology Care Providers on Survivorship Care: A Qualitative Study." The article presents research based on in-depth interviews with 32 Lymphoma patients and 13 oncologists. This is what a "qualitative" study is, as opposed to a "quantitative" study. Rather than giving a survey to a large number of patients and presenting the results as numbers, it looks at a smaller number of patients and looks for themes and patterns in their words. (Both types of research can be valuable.)

The research found three main themes. I don't think any of them will surprise you. The first is that Lymphoma patients often have a "profound fear of recurrence" and anxiety after treatment is finished. Patients wanted more information about signs and symptoms that their cancer might return, and more reassurance from their cancer team. 

The second is had to do with which doctor to see after treatment was "finished." Some wanted to continue to see an oncologist. Some were forced to see a primary care physician instead. Others saw the value of seeing a PCP but had trouble finding one. It's a complicated issue, and one that came up during the Follicular Lymphoma Foundation webinar that I spoke at earlier this month.  

Finally, during the interviews, it became clear to the researchers that formal survivorship programs were necessary, and that they needed to include psychosocial support, wellness services, and assistance with financial and employment programs to help survivors transition to their different lives. 

That last sentence was a hard sentence to write -- I tried "go back to their old lives," but there's really no going back. Then I tried "their new lives" but that's not right either, because it kind of implies that everything is OK after treatment is over, and it's not. So I went with "different lives," which I'm also not satisfied with, but which is probably more accurate than "old" or "new." And that pretty much sums up why survivorship is such a complex topic, doesn't it?

And I also recognize that "survivorship" is different Follicular Lymphoma survivors. That first one, the fear of recurrence, might be worse for us. If you're like me, you've been told since diagnosis that it's incurable, and we can expect to to come back. So maybe it's better, not worse, since many of us just accept that recurrence is inevitable and we can prepare ourselves for it?

 Like I said -- it's a complex topic. And it affects each of us a little differently. 

Which brings us to the more recent piece from JCOOP, published a couple of weeks ago, in response to the qualitative research above. It's called "Bridging the Gap: The Essential Role of Lymphoma Clinicians in Guiding the Transition From Lymphoma Treatment to Survivorship." 

As the authors of this piece note, one of the big issues related to survivorship is the lack of information that Lymphoma patients receive about what their lives will be like after successful treatment. That's certainly a factor in the fear that patients feel in that first theme. And its a factor in the second one, too, in the confusion about seeing an oncologist vs seeing a PCP -- will a PCP know enough about Lymphoma to be useful? Ideally, the type of information that patients receive would be personalized, since each of us does deal with survivorship in our own way.

Given that JCOOP is a medical journal for oncologists that work with patients, the recommendations from the authors are aimed at Lymphoma clinicians -- the oncologists that work most directly with Lymphoma patients. But they have lessons for us as patients, too.

Their first bit of advice for oncologists is to Prepare -- to start conversations with patients early, and continue them over time. Since patients tend to be focused on the present, it helps to gradually and repeatedly introduce the idea of survivorship over time, to let it all sink in. They suggest the use of Survivorship Care Plans -- a written record of your treatment and symptoms, including emotional symptoms, and how you'd like your concerns to be addressed. That's an excellent idea for us as patients -- consider creating one even if your oncologist doesn't suggest one formally.

The second bit of advice is to Acknowledge and Assess -- for the oncologist to ask questions about emotional well-being and fears, and to recognize that they are valid. As patients, we can help here by bringing them up even if the oncologist does not. I think it's also important to be prepared to have an oncologist that may dismiss them ("You have nothing to be worried about") or downplay them, or just not know how to deal with them. I like to think that someone in oncology would be well-aware of patients' fears, but I know that isn't always the case. Be open about it anyway. If nothing else, it will be a good education for the oncologist.

The third piece of advice for oncologists is Connect -- to be aware of survivorship services and help patients make contact with them. Again, as patients, we can ask questions about these kinds of services. They are often available, even if some oncologists don't know that. Pushing for information might make a less-informed oncologist seek out the information. And a well-informed oncologist will be able to pass on that information to you.

Finally, the last bit of advice for oncologists is to Evaluate and Document -- to ask patients how they are doing and make sure that their emotional well-being becomes a part of the permanent record. Again, we can help as patients by making sure that we bring up the subject ourselves. And it's not just emotional issues or concerns -- we should bring up physical issues, financial issues, anything that cancer has done to make our lives different.

As you can tell, I think the message to oncologists is interesting, but more importantly, I think the JCOOP piece provides an opportunity for us as patients. Some of us might be fortunate enough to be affiliated with a cancer center that has a survivorship program, and to have an oncologist that knows about it and intervenes early. Or maybe the opposite is true -- no program and an oncologist that isn't aware of the issues. Or maybe something in between.

Whatever the case, I think it's important for us as patients to be proactive. We need to be aware of our own needs, and unafraid to bring them up. If enough of us do so, it becomes a regular and expected part of our conversations with our doctors. That's good for all of us.

Stay well, and stay proactive.

FDA approval for Tafasitamab-cxix for R/R FL

The FDA has approved Tafasitamab-cxix (also known as Monjuvi) in combination with Lenalidomide (also known as Revlimid) and Rituxan for Relapsed/Refractory Follicular Lymphoma.

I wrote about this combination in November, just before the ASH conference. The results of a phase III clinical trial were being presented at ASH, and the website Fierce Pharma called the early results a "triumph." The makers of Tafasitamab had said immediately afterwards that they were going to seek FDA approval. And it came.

Tafasitamab had already been approved by both the FDA and the EU for use on R/R Diffuse Large B Cell Lymphoma, in combination with Lenalidomide.

Tafasitamab is a monoclonal antibody, like Rituxan. But Tafasitamab targets a different protein, CD19, on the surface of B cells (Rituxan targets CD20). The idea was that combining the two (along with Lenalidomide) would increase the chances that the treatment could find the cancer cells. That seems to have been the case.

The trial involved a direct comparison between Tafasitamab + Lenalidomide + Rituxan and a placebo + Lenalidomide + Rituxan. In other words, patients in the trial were going to receive either this new combination or just R-squared (Lenalidomide/Revlimid + Rituxan). Patients in the trial had already received at least one treatment for their FL already.

As Fierce Pharma said, the results were triumphant. After a median follow up of 14.1 months, the Progression Free Survival for the Tafasitamab combination was 22.4 months and 13.9 months in the other group. The Complete Response Rate was 49.9% for Tafasitamab and 39.8% for the other group, and the Overall Response Rate was 83.5% vs 72.4%.

The question with the combination was going to be about safety. Monoclonal antibodies like Tafasitamab and Rituxan work by eliminating B Lymphocytes, a kind of immune cell. They target both healthy B cells and cancerous B cells. So while having two antibodies targeting the same cells might mean it's more effective, it also means you're running the risk f having too many immune cells being disabled all at once, opening up the possibility of greater risk of infections.

And that did happen. In their announcement, the FDA points out that "serious adverse reactions occurred in 33% of patients" in the Tafasitamab group, including serious infections in 24% of participants.The announcement doesn't give a direct comparison to the other group in the trial, though the ASH presentation did -- 36% of the Tafasitamab group vs 32% for the other group (the FDA numbers are a little different because they were updated 6 months later). Also in the ASH presentation, it was noted that during the study, 15 patients in the Tafasitamab group died, 5 because of disease progression and 6 because of side effects, versus 23 in the other group (17 due to disease progression and 6 from side effects). 

It will be interesting to see how popular this combination becomes with oncologists. Will this become a substitute for R-Squared? Similar way of working, but more effective? Or will some patients still be given R-squared instead because it seems slightly less aggressive on the immune system? (Remember, I'm not a medical doctor -- these are just questions that are coming to me immediately after reading this). I look forward to reading more commentaries in the coming weeks and months.

ASCO: Exercise and Cancer

A reader left a comment on my last post that I want to address here, rather than in the comment section:

Thank you for ASCO coverage. Seems ASCO's headline grabber this year was the "Structured Exercise Program Improves Survival Outcomes in Patients With Stage III or High-Risk Stage II Colon Cancer" story. Do you think this study translates to FL folks, especially in terms of recurrence and survival? I just noticed current Mayo study along the same lines for indolent NHL lymphomas CLL and MZL. Any "there" there?

I have been reading about this presentation, and I was considering writing about it (especially since there is so little to write about Follicular Lymphoma this year. 

My quick take on it is this -- it's a study that describes a very specific research project, and was reported with some headlines that make it seem to affect many more people than it actually does. It is both excellent research and a good lesson in reading carefully.

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Let me start off with one of the headlines that describe this study (from NBCNews.com, which shouldn't be so clickbaity): "Exercise may benefit colon cancer patients as much as some drugs."

Now, clickbait is a headline that is meant to get you to click on it and visit the page. If I'm being fair, the title I'm using for this blog post is kind of clickbaity, but that's the point -- the title doesn't fully represent what the content of the article says, exactly. There were a lot of articles that did something similar, speaking in very general terms about the study to make it more attractive to readers. It's a very common tactic in popular science writing. The NBC News headline makes it sound like exercise is a substitute for more traditional cancer treatments for anyone with colon cancer.

That's not the case. Exercise didn't cure anyone's cancer.

But that's not to say it isn't an important study. From what I read, when the presentation was finished, the oncologists in attendance actually gave a standing ovation. So what the study actually says is still pretty important.

The presentation is #LBA3510 "A randomized phase III trial of the impact of a structured exercise program on disease-free survival (DFS) in stage 3 or high-risk stage 2 colon cancer: Canadian Cancer Trials Group (CCTG) CO.21 (CHALLENGE)."

The study looked at 889 patients with colon cancer from Canada and Australia, median age 61. About 90% of the patients had stage III colon cancer, and the other 10% had high risk stage II. The patients all had surgery followed by adjuvant chemotherapy (that is, chemo that was meant to "clean up" any remaining cancer).

It's worth repeating this, given the headlines -- all of the patients had surgery and chemotherapy. Traditional cancer treatments played a huge role in making them cancer-free. Exercise did not cure or prevent their cancer, at least in this particular study.

After chemotherapy, patients were split into two groups. The first group was given Health Education Materials (the abstract calls this the HEM group) that promoted good nutrition and exercise. The second group was given a Structured Exercise Program (they are the SEP group), supervised by a Physical Activity Consultant, who met with them twice each month for three years. The specific physical activity was chosen by the SEP patient. It could have been working out in a gym or it could have been just walking for 45 minutes per day. But it was structured, supervised, and done regularly. 

The results were fascinating. With a median follow-up of almost 8 years, 93 patients in the SEP group had their cancer come back, compared to 131 in the HEM group. After 5 years, the disease-free survival (DFS) was 80% for the SEP patients and 74% for the HEM patients. The 8 year Overall Survival was 90% for SEP and 83% for HEM.

This was a fairly large stage 3 clinical trial, not just observations or reports from patients, and that's what makes it so impressive. The patients in the trial reported in with their consultant every two weeks for 3 years. All of this is enough to make it pretty clear that the difference in the two groups with the physical activity that one group performed. Exercise didn't cure anyone's cancer, but it might have helped keep 90% of the patients alive for 8 years.

Now, I want to be clear about something else -- the reader who left the comment wasn't implying that exercise alone was a replacement for conventional treatment. The reader is clearly reading carefully, even referencing another Mayo Clinic trial on blood cancer. That reader is being careful.

That said, I don't know the answer to their question, Do you think this study translates to FL folks, especially in terms of recurrence and survival? I just noticed current Mayo study along the same lines for indolent NHL lymphomas CLL and MZL. Any "there" there?

This is a good time to once again remind everyone that I am not a medical doctor, and the best person to ask about treatment and lifestyle choices is your own oncologist. 

But I will say, for what it's worth, as a non-expert, I think exercise is an excellent idea, whether you are watching and waiting, in active treatment, or post-treatment. Moving our bodies is always a good thing. 

One of the great details from this study is the range of exercise that the participants engaged in, and the fact that it was their choice. I've heard it said that the best exercise that you can do is the one that you enjoy enough to keep on doing it. Sometimes when we think of a "structured exercise program,"  we imagine going to a gym and having a trainer yell at us as we push large amounts of weight. If that's what you enjoy, keep doing it. But if a 2 mile walk every morning is your thing (as it is with my wife and me), then keep that up. And if you have physical issues that make that harder, then find something else -- a shorter walk, or chair yoga, or water aerobics. But keep moving.

The best part of all of this was the enthusiastic reaction of the oncologists in attendance. I hope this means there will be follow-ups -- more rigorous studies on the benefits of exercise, whether it's post-treatment or during treatment. 

So I certainly hope there is some "there" there. We'll know for sure when the results of the Mayo trial get presented or published.

In the meantime, I encourage you to do two things:

1) Read carefully.

2) Keep moving.

More soon. 

 

ASCO: Amulirafusp alfa

 As I have been saying, there really weren't a lot of presentations on Follicular Lymphoma at ASCO this year, and most of them have been focused on treatments that are already established.

But there is at least one presentation on a newer treatment. It's one that I haven't written about before. (To be clear, I'm not saying that I manage to write about everything FL-related. But this is definitely one that I haven't mentioned before.)

The presentation is Abstract #7051: "Phase II safety and preliminary efficacy of amulirafusp alfa (IMM0306) in combination with lenalidomide in patients with relapsed or refractory CD20-positive follicular lymphoma." I actually remember reading about this when I looked at abstracts from ASH in November and December, but for whatever reason, I decided not to write about it. The ASH presentation looked at phase 1 trial results. This one looks at phase 2 results.

In this research, a treatment called Amulirafusp Alfa is given in combination with Lenalidomide (also known as Revlimid, one of the Rs in R-Squared). Amulirafusp Alfa is a very interesting treatment. It worls in ways that are similar to a bispecific, but it isn't a bispecific (which attaches to a protein on a lymphoma cell, and to a protein on a T cell, a kind of immune cell, bringing them together so the T cell can elimiate the cancer cell).

Amulirafusp Alfa works by targeting two proteins on the lymphoma cell. One of them is CD20, the same protein that is targeted by Rituxan and by some bispecifics. But it also targets CD47, another protein on the cell. By attaching to CD47, it blocks something called SIRPα (Signal Regulatory Protein a). When CD47 and SIRPα interact, they send a "Don't Eat Me" signal to the immune system. When that interaction is blocked, the immune system can eliminate the lymphoma cell.

And just as a bispecific is an immunotherapy -- it allows the body's T cells to work against cancer cells -- Amulirafusp Alfa allows other (even more powerful) immune cells to work against the cancer cells, in this case Macrophages and NK/Natural Killer cells.

This phase 2 trial involves 34 patients with Relapsed/Refractory FL. All of them had a previous treatment with anti-CD20. In the study, 22 patients were evaluated; 10 of them had a Complete Response (45%), 8 had a Partial Response, making the Overall Response Rate 82%; 2 more had Stable Disease. As for safety, the side effects were considered "well-tolerated," with most pateints having descreased blood cell counts of different types, another 35% having an infusion-related reaction. About 65% of patients had a more serious (grade 3 or higher) side effect. 

It certainly seems like a promising treatment, one that works in ways that are different from what we have seen so far.  It will be interesting to see updated figures (only 22 of the 34 patients in the phase 2 trial were evaluated), and to see how this treatment goes in a larger phase 3 trial.

Definitely one to keep an eye on.

ASCO: FL Subtypes

 Before I get to another ASCO presentation, I want to provide a link to the webinar I helped with last week for the Follicular Lymphoma Foundation.

The webinar is called "FL Treatment Options: What You Need to Know." It features Professor Andrew Davies of  the University Hospital Southampton in the UK, who did an amazing job of explaining the treatment options available to us in  an easy-to-understand way, and Dr. Mitchell Smith, the Chief Medical Officer for the FLF, who asked great questions and found ways to connect what I was saying as a patient and what Prof. Davies had to tell us as a Lymphoma expert.

I really enjoyed doing it, getting to share my experiences as a patient. I really like the messages that the FLF tries to get across, especially the importance of being an informed patient who can have a good conversation with their oncologist and ask the right questions. We have a lot to be hopeful about. 

The webinar is about an hour long. I hope you can find some time to watch it. 

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Now, on to the ASCO abstract for today.

I was really interested in #7070 "Clinical and biological subtypes of follicular lymphoma revealed by tumor and immune cell states."

As you read more about Follicualr Lymphoma, one word that you see over and over is "heterogeneous," which basically means that there are lots of different types of FL. If you spend any time in an online group for FL patients, you'll see how this plays out. You'll have someone like me who could watch and wait for a couple of years and then have a very long response from just Rituxan, And you'll also encounter someone who had a very aggressive FL who needed traditional chemo and maybe several other treatments after that. And you'll have other patients with experiences somewhere in between. 

This heterogeneity of the disease makes it a challenge to treat. Very often, patients don't know if a treatment will work until they've had the treatment. In an ideal world, we'd have a better sense of that before treatment began, perhaps by a biomarker. A biomarker is some biological component (maybe a certain protein on the cancer cell, for example) that would let the doctor know that a certain treatment is more likely to work, or maybe more likely to be aggressive or transform, allowing the doctor to at least narrow down the choices of treatment. We don't really have that yet.

Every now and then, someone proposes some kind of scheme for classifying Follicular Lymphoma into subtypes, allowing us to have a better sense of what we might expect. FL will always be heterogeneous -- that's unavoidable. But it would be great to more accurately categorize that heterogeneity.

This ASCO presentation is the latest attempt to do that. They try to create categories of FL based on characteristics of the cancer cells themselves, but also characteristics of other immune cells. They looked at several thousand samples of FL cells, and found four different subtypes of FL. It's kind of hard to distinguish the four types, and in some ways, the details don't really matter at this point. It will require a larger study to see what the real world implications are, and if this proposed scheme even holds up.

They do identfy two possible future targets for future treatments -- CREBBP (CRE-Binding Protein, which is involved in cell growth) and PRDM15 (a protein involved in differentiation, where an immature cells grows into a specific type of cell).

Will those targets result in new, effective treatments years from now? Will the subtypes hold up and help doctors make better treatment decisions? Hard to say, at least for now.

But what I find most interesting is what it all says about where we are right now. For all of the progress that has been made in developing new treatments, there is still so much that we don't know.

And I find that oddly comforting. If researchers said "Well, it looks like we've tried everything, and nothing works," that would be sad. But we're constantly getting new possibilities, learning more about FL, even when things don't work out as we'd hoped. Researchers will hit on something soon -- maybe not tomorrow, maybe years from now. But we're always moving forward. I find that really hopeful.

More ASCO stuff soon.

(And remember to watch that FLF webinar when you get a chance.)

ASCO Review: Clinical Trials and Surrogate Endpoints

As I said in my last post, this is kind of a lean year for Follicular Lymphoma at ASCO. There are far fewer presentations on FL than there have been in the recent past. And no "blockbusters" -- no major studies that are being presented with new information about new treatments that we haven't seen much of (though there is one that presents data for a new treatment that I will get to soon).

Instead, most of the the FL presentations at ASCO are about refinements -- new information about treatments we are already familiar with. In truth, that's what most ASCO (and ASH) presentations every year are about anyway, and that's not a bad thing. Clinical trials can only give us a certain amount of information, and after a treatment has been approved, there's still plenty we need to know about long-term effectiveness and side effects and "real world" factors. 

So while there isn't too much this year with a high "wow factor," there is some interesting stuff to talk about.

One study is called "The clinical trials landscape in follicular lymphoma: A systematic review." It looks at how clinical trials for FL treatments are conducted and the complications that come with a disease like ours.

Some background: a clinical trial is a way of systematically testing a treatment, and ideally allows us to compare treatments to one another by looking at effectiveness and safety. The problem comes in how effectiveness is measured.

In an ideal world, we would measure by Overall Survival, or OS. In other words, we look at how many people are still alive at the end of the trial, and if there are more alive than there were in a trial for a different treatment, then we know the new treatment is better. That seems like the best way to measure the effectiveness of a cancer treatment -- it keeps people alive.

The problem, at least for FL treatments, is that FL patients tend to live a long time. The median OS, as presented by the researchers who did this study, is "over 15 years." So more than half of FL patients will live for more than 15 years after diagnosis. That's great for us patients, but less great for those who are developing treatments.

The reason is practical. If researchers have to wait 15 or more years to accurately measure OS, that means it's going to be even longer before they can get approval for their treatment and start making money off of it. That's a legitimate concern. As much as I'd love people to develop treatments based only on their love of science and their genuine concern for cancer patients, the reality is that someone has to pay for all of that research, and they want there money back. If they have to wait 15-20 years, there is much less incentive for them to invest in the first place. That's the reality.

So researchers develop "surrogate endpoints." They try to find some other way of measuring effectiveness that won't take so long. So they can say to the FDA or other regulator, "Our surrogate endpoint is 5 year PFS. If someone is able to go for 5 years without the disease progressing, then we can assume they will have a long Overall Survival." It's not a perfect system.

This ASCO presentation looks at the different surrogate endpoints that researchers have been using in FL trials. It identified 28 phase III clinical trials involving FL. It found that 79% of the trials used Progression Free Survival as its primary endpoint, with 18% using Overall or Complete Response Rate. Other surrogate endpoints included Progression Of Disease within 24 months (POD24), Complete Response at 30 months (CR30), and Minimal Residual Disease (MRD). 

About 50% of the trials included some measurement of Quality of Life, which wouldn't count as an effectiveness measure, but it's definitely a good thing to look at.

Also, about 50% of the trials involved CAR-T or Bispecifics, which brings up the possibility that Overall Survival for FL patients may increase even more. Again, that's an excellent problem for us to have, but it is still a problem, in terms of research. The researchers call for more research into how effective surrogate endpoints are, and perhaps finding new ones that will do a better job.

So while it is frustrating to know that our clinical trial system needs some improvement, it's also good to know that the reason is we are living longer, a s group. For now, that seems like a pretty good trade-off, but moving toward a more perfect system should remain the goal.

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One last reminder:

Remember that I'll be one of the speakers the Follicular Lymphoma Foundation's webinar, "FL Treatment Options – What You Need to Know," taking place Thursday, June 5, at 12:30 Eastern Time.

You can read more about the webinar and register at this link: https://us02web.zoom.us/webinar/register/2617476619964/WN_S3L8Al8tQAOjPWBy6ERxCw#/registration

There will be a recording posted later if you can't make it (or you're seeing this too late).

Hope to see you there!

 

 

ASCO Review: Treatment Preferences in FL

It's finally time to get to some ASCO reviews.

As I said in my last post, there seems to be a much smaller number of presentations about Follicular Lymphoma this year than in the past. Not sure what that's all about. There's a major Lymphoma conference in a few weeks in Lugano, Swtzerland, and a smaller one in Texas pretty soon, so maybe researchers for those instead. I haven't seen any discussion of it online. Not a bad thing; I'm just curious.

So, as I have been promising, the first one I will look at is one that I have a co-author credit for: Abstract #11109, "Treatment preferences of patients, caregivers, and physicians in follicular lymphoma (FL): A global discrete-choice experiment (DCE) study." Authored by Mitchell Smith, Mei Xue, Erlene Seymour, Yan Meng, Julie Dodds, Todor Totev, Leah McAslan, Andrew McAslan, Robert McEachern, Paul Mollitt, Lilian Diaz, FengYi Jiang, Krysten Klein Brand (KKB), Dominic Pilon, and Keri Yang.

I don't want to misrepresent myself here. The presentation is a poster detailing the results of a survey of FL patients, their caregivers, and some oncologists. There were obviously many folks involved, and the doctors and statisticians and writers did most of the work. But there were three patients and one caregiver who added enough of our perspective on how to ask questions and what the answers meant that we earned co-author credit. Mostly, it's just really cool to see my name on an ASCO presentation abstract. 

As I said, this presentation give the results of a survey, and some of you may have taken part in it. Last November, I posted a link for the survey. If you took part, you probably remember, because it's kind of an unusual (but really interesting) way of asking people for preferences. It's called a "discrete choice experiment." In this type of survey, you are asked to make a series of choices between direct comparisons. So you might be asked if you preferred a treatment that might give you 5 years of remission, but with severe side effects, and would require 1 hour of travel? Or would you choose 2 years of remission, with mild side effects, and 3 hours of travel? The survey asks you to choose between the two. And then it gives you 10 more comparisons, with different years of remission, different side effects, and different travel times.

The idea is that you are being forced to make priorities. And those forced choices will show up as a pattern. Combine all of those choices and patterns from everyone who took the survey, and you can see larger patterns that tell you something about how patients, caregivers, and oncologists make choices about treatments.

Specifically, the survey asked questions about efficacy of treatment (how long the treatment would result in Progression-Free Survival), safety (the impact of side effects including fatigue, cytokine release syndrome (CRS), and nerve-related issues on quality of life), and convenience (the way the treatment is administered, how long the treatments take, and the time needed to travel to the treatment center). The choices aren't real treatments, just hypotheticals to get people to make a choice and create a pattern.

The survey was completed by a total of 337 patients, 37 caregivers, and 29 oncologists from 25 countries.

There were some interesting differences in the way the groups responded.

 Patients preferred treatments with a longer Progression Free Survival, mild or no impact of fatigue, CRS, and Nerve-related events. They preferred oral tablets over infusions. And they would rather have treatment twice per week for three months rater than ongoing treatment forever with a doctor's appointment every 3 months. And they'd prefer as short a travel time as possible.

All of that makes sense for patients. There's a kind of "let's get this over with" attitude that lots of us have. 

All three groups (patients, caregivers, and doctors) ranked PFS as most important. Again, this isn't very surprising. We all want our treatments to be effective for as long as possible.

But after that, there was a little bit of a difference. For patients and caregivers, the next most important thing was treatment convenience (oral tablets, less time in the doctor's office, and less travel time). But for the oncologists, the second most important thing was safety (less severe side effects). 

This makes sense, too, in many ways. The doctors who took the survey were mostly oncologists who saw patients and also did research. In a clinical trial, efficacy and safety are the most important things, so maybe that's what they are kind of trained to look at. For patients and caregivers, the treatment experience is about making it all as easy as possible, and getting it over with as quickly as possible, and moving on. 

That difference in preference should not be seen as oncologists not caring about patients' day-to-day lives. Quite the opposite. But they see that caring through a different lens. Quality of Life matters for all three groups; it's just playing out differently, based on lived experience.  

One last bit of statistical analysis that hit me hard:

"On average, patients were willing to accept reductions of 1 y of PFS for treatment requiring <30 min of travel vs >2 h, 0.7-1 y to receive treatments with less impact of AEs on QOL, 0.6 y for oral tablets vs blood collection and intravenous infusion, and 0.5 y for 3-mo treatment vs continuous duration."

As I said this is statistical analysis. No one was asked "You say you want 5 years of PFS. But how many months would you knock off that number if it meant you could take a pill instead of an infusion, or you'd have to travel for 30 minutes instead of 2 hours?" I don't think I could answer that question directly. I'm not sure any of us could. 

But that's what makes a discrete-choice experiment so interesting. By making choices, we create patterns, and someone looking carefully at those patterns can say "Reducing travel time means you'd be willing to need treatment again one year sooner than you otherwise would." It's fascinating to me.

The conclusion to the abstract is incredibly important: "Insights on differences between preferences highlight the importance of informed discussion and a balanced, individualized approach to treatment selection."

We al want the same thing, whether we are patients, caregivers, or doctors -- to knock out this cancer for as long as possible, and to do it as safely as possible while disrupting the patient's life as little as possible. But how much we value those things is going to be different for each of us. Having a conversation about it with our doctor is so very important, so everyone knows what is important when those decisions have to be made.

It was a great experience to be a part of developing and analyzing this survey, and I am appreciative of those who asked me. I hope I'm able to do something like this again in the future.

But for now, I'll keep reading and reviewing this year's ASCO presentations on FL. I'll have more for you soon.

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One more thing -- remember that I'll be one of the speakers the Follicular Lymphoma Foundation's webinar, "FL Treatment Options – What You Need to Know," taking place next Thursday, June 5, at 12:30 Eastern Time.

You can read more about the webinar and register at this link: https://us02web.zoom.us/webinar/register/2617476619964/WN_S3L8Al8tQAOjPWBy6ERxCw#/registration

Hope to see you there!

 

I'm Back! There's Work To Be Done!

I'm back again, and ready to write some more!

My wife and I just spent 10 days in Europe on a river cruise down the Rhine. A few days in the Netherlands, then Germany, France, and Switzerland. We saw many cool things, ate good food, and met interesting people. 

We've been trying to make travel a priority. We went to Italy a couple of years ago, and we starting planning our next big trip on our way home from this one. We were both lucky when we were much younger to have been able to travel, and that got harder after we had kids. Now our kids are grown, and we think about the health issues that both of us have. I'd be very sad if, one day when we're older, we looked back and say "Remember when we used to talk about traveling? That would have been nice." We don't want that to happen.

So we do what we can to make it all work. Traveling takes time, and money, and energy -- and there are times when it seems like we don't have much of any of those things. But we decided to prioritize these experiences.

To put this in cancer terms -- that's kind of what Survivorship is all about, isn't it? It's about making decisions that let us live the life that we want, on our own terms. So we'll keep driving our 12 year old car as long as we can. I'd rather drink a Kölsch in Cologne than impress the neighbors with a new CL55.

As I said, we met some wonderful people on our trip, especially a group of four from Pennsylvania, two couples who are lifelong friends. They truly made the trip something special. We enjoyed spending time with them.

And of course, as you get to know someone, there is almost always a cancer connection. It's hard to escape. One of our four new friends is a three-time cancer survivor. We shared stories -- of the awful things people have said to us about cancer, and of the importance of trying to laugh sometimes. But mostly we didn't talk about cancer. We drank wine and talked about our kids and won a trivia contest. Like I said -- survivorship. 

I hope you are all able to do the things that make you happy. It feels very good.

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I have been able to look at the ASCO abstracts for this year, and so far, I'm not seeing much about Follicular Lymphoma. I'll start reviewing them soon, including the one that I am a part of (I know I've been promising that -- I'll get to it very soon).

In the meantime, the Follicular Lymphoma Foundation has put out the official announcement for their webinar next week. Here's one of their social media posts:

 

 

I'll be one of the speakers for the webinar, which is happening next Thursday, June 5, at 12:30pm Eastern Time. I'll talk about my Follicular Lymphoma treatment experience. You'll also hear from Dr. Mitchell Smith, the Chief Medical Officer for the Follicular Lymphoma Foundation, and Prof. Andrew Davies, Professor of Haematological Oncology at University Hospital Southampton. They're both going to be fantastic. 

You can read more about the webinar and register at this link: https://us02web.zoom.us/webinar/register/2617476619964/WN_S3L8Al8tQAOjPWBy6ERxCw#/registration

If you have questions for any of the panelists, you can submit them on the registration form. 

And if you can't make it to the webinar, the FLF will post a recording on their website after it is over.

I'm really looking forward to it. The FLF is a great organization, and I'm honored that they have asked me to be a part of this. 

It's good to be back. More to come very soon.