Follicular Lymphoma Year in Review

Looks like this is going to be my last blog post of the year. 

I'll save any words of wisdom for a couple of weeks from now, when I do my diagnosiversary post (though I'm not promising anything to wise). But I did think it might be nice to look back at the year.

I'm going to let an article from Medpage Today do some of the work for me. "Year in Review: Follicular Lymphoma" was published December 1, but it covers some of the good some of what happened this year for FL.

The subtitle for the article is "A Promising Year for Bispecific Antibodies," and that is indeed the focus of the article. Though the article says that the year began with the FDA approval for Mosunetuzumab, that actually happened in late December 2022. But since the article was published a month before the end of the year, we'll forgive them for getting their dates mixed up.

The important thing is, the bispecific was improved, and the numbers from the clinical trial were great -- an Overall Response Rate of 80%, with Complete Responses of 60%, and a median duration of almost 2 years. Those are very good numbers, and follow-ups and expanded studies of Mosunetuzumab just confirm this (I'll try to write about one of the follow-up studies soon).

In addition to the approval, bispecifics as a class got more good news from the FDA, with Glofitimab getting accelerated approval in July for Diffuse Large B-Cell Lymphoma, including patients whose FL had transformed (I didn't write about this in the blog), and Odronextamab getting priority review in October from the FDA based on its phase 2 trial. Great numbers here, too -- ORR of 82% and CRR of 75%, with the CRs lasting a median of 20.5 months. 

And finally, the FDA gave breakthrough designation for Epcoritamab, yet another bispecific antibody.

The other bit of news that the article gives is the PI3K inhibitor Copanlisib being pulled from the market in November. I've written enough about that already -- no more comment.

In terms of FDA approvals, that about covers what happened for the year. But I think there were lots of other good things, too. Progress happens in small steps -- sometimes smaller than we'd like. But those small steps are worth celebrating, too.

So I would add a few more things to the year in review.

• Phase 2 trial results for Liso-cel were very positive. An eventual approval would give us a third option for CAR-T treatments.
• The FDA has accepted a supplemental Biologics License for the combination of Zanubrutinib (a BTK inhibitor) and Obinutuzumab (a monoclonal antibody) for patients with R/R Follicular Lymphoma. A decision should be made in the next couple of months.
• Subcutaneous Rituxan performed very well in a phase 3 trial. Approval could mean less time and lower costs for those receiving the treatment.
• Rituxan celebrated its 25th birthday.

These are all excellent things. Looking at the headlines from conferences like ASH and ASCO, it seems like DLBCL and Multiple Myeloma had excellent years compared to FL. Lots of bigger steps forward for them.

But I'm OK with our little steps forward. Good things are continuing to happen for FL patients, and many more good things are to come. 

I hope you all have a very happy new year. I look forward to sharing more with you in 2024.

Peace

Sometimes I write a message on this day, Christmas Day. I know many of you celebrate and many don't. I do. But the message I like to send on this day is one that, I hope, is appropriate no matter what faith one follows, if any.  

As I've said in the past, there are lots of phrases and greetings associated with Christmas. You see them on gift tags and bags, on cards, on posters in stores. Of all of them, my favorite has always been "Peace on Earth." It's usually a wish, a desire, rather than an observation. This year is no different. Maybe even worse than usual -- there's so much division in the world. Some people can't even agree on which greeting to use for Christmas. And that's not even considering the war and violence going on in the world, and the division that happens as a result, thousands of miles away from it. 

This is a tough time to find peace.

And my message on this day usually connects that desire for peace on earth with a need for peace inside ourselves. That hasn't changed. In fact, with so much going on outside of us, there's probably a greater need for peace inside of us. Stress takes its toll on a cancer patient. We all need a break. Now more than ever.

After almost 16 years of living with Follicular Lymphoma, I wish I had some better words of wisdom than I do. But it seems like the wiser I get, the harder the problems around me seem to get. 

I just re-read that last paragraph, and I corrected a word I had misspelled -- I had said "After almost 16 years of loving with Follicular Lymphoma." And I suppose that's true, too. I've been doing my best to spread some love for all of that time. It's strange how writing a blog post about radioimmunotherapy or tazemetostat can be an act of love, but here we are.

And I suppose that's the message, in the end. When it comes to living with Lymphoma, we need to find our own path to inner peace. I've always believed that we each need to live our lives as cancer patients in the way that makes most sense to us. Our path to inner peace has to be our own path. It needs to make sense to us.

So on this day, my biggest wish for you is that you find your path to peace, whatever it might be. 

And maybe, if enough of us find our own peace, it makes the world just a little more peaceful. Not entirely peaceful -- I'm nothing if not a realist. Just a little more peaceful. I'll be happy with that.

Merry Christmas to those of you who celebrate it. Happy holidays to those of you who celebrate other days, weeks, and months this time of year. 

And peace to all of you.

 

ASH Review: Mosunetuzumab for Untreated FL

 Another ASH presentation that has some lymphoma experts excited:

604: Subcutaneous Mosunetuzumab As First-Line Therapy for Patients with High Tumor-Burden Follicular Lymphoma (FL): First Results of a Multicenter Phase 2 Study.

 As you probably know, Mosunetuzumab is a bi-specific antibody. It's a lot like Rituxan, in that it attaches to the same CD20 protein on the surface of a cancer cell. But it also attaches itself to a protein on a T cell, an immune cell that can eliminate the cancer cell when it gets close to it. Bi-secifics are one of those newer treatments that get lymphoma specialists very excited. Mosunetuzumab is already approved by the FDA for FL patients with Relapsed/Refractory disease (just about a year ago). 

This research looks at a different population -- untreated patients, though those with high tumor burden (about 72% had stage 4 disease). There was also a different delivery method -- subcutaneous, an injection, rather than intravenous. 

The study looked at 43 patients. The title says "First Results," and these are indeed very early results -- some patients in the study haven't even been evaluated yet for how effective the treatment has been for them.

Of the 26 patients that have been evaluated so far, the Overall Response Rate has been 96%, with the Complete Response Rate at 81% ( that's 22 out of 26, and all 22 were seen at the first response assessment, meaning the treatment worked very quickly). Responses were also durable. At 6 months, 2 patients had disease that progressed (one of them transformed to DLBCL), but the rest of the group had remained stable or in remission.

A larger group were able to be evaluated for safety -- 39 patients. In this group, the most common side effects were problems at the injection site (72%), Cytokine Release Syndrome (51%), fatigue (33%), dry skin (33%), and skin rash (26%). More serious neutropenia (low white blood cells count) occurred in 10% and infections occurred in 26%. One patient died of cardiac arrhythmia while being treated for COVID19-associated pneumonia. Only 2 patients needed to be hospitalized with CRS. 

So overall, this is really great data to make the case for Mosunetuzumab for untreated FL. One of the researchers pointed out that more data is needed to show that it is effective over the long term. 

An article in Healio called it "remarkable" and  "highly encouraging" (though it doesn't say who exactly is being quoted). 

Lots of good news lately in the world of bi-specifics. I'm sure we'll be seeing even more in the near future.

 

ASH: Acalabrutinib and R-Squared

Many thanks to longtime reader William, who learned about a promising Follicular Lymphoma treatment from an email from MD Anderson. This one was discussed at ASH, and it's worth highlighting. 

The ASH presentation is "#983: Addition of Acalabrutinib to Lenalidomide and Rituximab Induces High Complete Response Rates in Patients with Previously Untreated Follicular Lymphoma: Results of a Phase II Study." 

To break down the title a little bit -- if you've been reading for a while, you are familiar with R-Squared, or the combination of Rituxan and Revlimid (or Lenalidomide). It was shown to be a viable alternative to traditional chemotherapy. It's very good, but could be better (like every other FL treatment). This research looks at adding Acalabrutinib.

The logic makes sense. Alcalabrutinib (also known as Calquence) is a BTK inhibitor. Like all inhibitors, its job is to inhibit, or stop, something from happening. In this case, the target is Bruton's Tyrosine Kinase, an enzyme that is necessary for B cells to develop. As you probably know, B cells are immune cells that can cause a number of B cell lymphomas (including Follicular Lymphoma) when things go wrong. Alcalabrutinib stops one of the processes that allows B cells to grow unchecked. 

BTK inhibitors should make sense for B cell lymphomas like FL. Indeed, Alcalabrutinib has been approved in the USA and in Europe for other B cell lymphomas like CLL and Mantle Cell, both indolent like FL. But for some reason, BTK inhibitors just haven't been as effective on FL as it has with those other lymphomas. (Ibrutinib, also known as Imbruvica, was the first major BTK inhibitor, and has also been very successful for some other lymphomas, but not for FL.)

So maybe the trick is to use it in combination with another successful treatment?

This ASH presentation does present some good evidence for that. 

As the researchers point out in the abstract, they have already had some success with this combination with FL patients with Relapsed/Refractory disease. For this research, they tried the combination on untreated FL patients. It's a phase 2 trial, so there is a relatively small group of patients involved (just 24 of them).  As the researchers explain, one possible reason that R-squared might not be effective is because of "pro-tumoral macrophages." A macrophage is a kind of heavy-duty immune cell -- when B cells and T cells don't work, macrophages take over. But cancer is all about things not working the way they are supposed to, and macrophages can become "pro-tumoral" -- working to protect cancer cells, not eliminate them. BTK inhibitors like Alcalabrutinib can help keep macrophages from protecting tumors.

The small phase 2 study was pretty successful. The Overall Response Rate was 100%, and the Complete Response was 92%, with a median time of 3 months to the CR. As for durability, after a median follow-up of 26.8 months, 6 patients had their disease progress, including two whose disease transformed. After 2 years, Progression Free Survival was 79.2%, and Overall Survival was 91.7% (two patients dies, one from Covid).  The most common serious side effects (grade 3-4) were neutropenia (low neutraphils, a type of white blood cell, 58%), liver function test elevation (17%), infection (12.5%; 2 out of 3 related to COVID19), anemia (8%) and skin rash (8%).

The researchers also point out that some blood cells had changed in ways that indicate that BTK was being inhibited.

So overall, it seems like a promising treatment. The researchers think so, too -- they are expanding the trial from 24 patients to 50. I hope we'll see updated results next year.

Thank you again to William for pointing this one out. We're getting to the point where people will be looking back at the conference and writing and talking about what excited them. I'll keep sharing.

ASH: Leonard's List/Quality of Life

The ASH conference is happening this weekend, so I can't really call these "previews" now. I'm far behind in my attempts to write about what's happening there.

For this post, I'm looking at "Leonard's List." This is the annual list of the Top 10 presentations at ASH, in the opinion of Dr. John Leonard, a blood cancer specialist at Weill-Cornell in New York. I like Dr. Leonard a lot. He is as good as it gets when it comes to expertise, and he explains things very clearly for a non-expert audience. 

So every year, in the 10 days before ASH begins, he releases the next entry on his Top 10 List on Twitter/X. Then he does a podcast episode on the Weill-Cornell CancerCast where he goes into a little more depth on the whole list. 

He does mention a couple of Follicular Lymphoma-related presentations on the List, but I was surprised to see that an FL presentation was one of the ones that tied for his top spot. 

The presentation is called 3761 Frontline Management Strategy and Quality of Life in Follicular Lymphoma: A Multi-Institutional Prospective Cohort Study.It came in as co-number 1 with a similar study of Quality of Life for patients with CLL, another indolent, slow-growing, incurable blood cancer. 

The presentation looks at 1544 FL patients who have Quality of Life data available (along with information on disease status, health behaviors, and functional assessment, treatments, disease relapses, and deaths). All of this information was collected by surveys that the patients took when they were diagnosed and then every year after that, along with medical records. The idea was to try to measure changes in the patients' lives that could measure their Quality of Life -- the physical changes to their bodies as a result of the cancer and its treatments, but also the emotional changes that they went through. 

They divided up the patients into three groups, based on how their disease was managed at diagnosis -- Observation (those who watched and waited), Treatment (those who received systemic treatment right away, like chemotherapy or immunotherapy), and Local (those who had radiation right away).

The results were very interesting.

The patients in the Treatment group had the worst measure of Quality of Life at diagnosis. This makes sense -- patients who watched and waited probably had less aggressive disease, and those in the radiation group were likely stage 1 or 2 with fewer symptoms.

But as time went on, the watch and wait and radiation groups had a lower Q of L as time went on, probably because their physical symptoms got worse. Also interesting -- for all three groups, some of the less physical measures got worse over time, including social/family relations and emotional well-being. 

In some ways, all of that makes sense. I know from experience and fro talking to so many of you that watch-and-waiters can feel the emotional burden of their decision over time. We get used to it, but for many of us, knowing that we have cancer but not actively treating can have a real negative effect on us.

So why did Dr. Leonard include both of these studies as his #1? Well, the CLL patients in the other study (remember, it's an indolent lymphoma, and lots of CLL patients watch and wait, too) study had the opposite results -- their Quality of Life improved over time. 

Dr. Leonard has a few things to say about this.

First is that we need to consider the value of early treatment. In other words, doctors often recommend watching and waiting for patients with FLL or CLL or other indolent blood cancer, assuming it's always a good thing. No treatment (and thus none of the physical side effects) is a good thing, right? 

Maybe that's not always the case. Maybe the better approach would be to determine the circumstances for individual patients. Some of us might be better off with treatment right away, even if the disease is stable and their isn't a physical need.

For what it's worth, I've been telling other FL patients this for a long time. If the emotional (not just the physical) symptoms suggest that treatment is better -- because the emotional burden of living with cancer without treating it might be too much -- then treatment should be an option. And for patients who have watched and waited for a few months, who discover that it's just too hard to live with, delayed treatment should be an option, too.

The other big lesson?In Dr. Leonard's wise words:

"But this really highlights the fact that we need to focus in follicular lymphoma and in CLL for watch and wait patients in particular, but in all patients, we need to have better tools to focus on quality of life because frankly for many patients who will not die of these diseases, but with these diseases, targeting quality of life and the choice of to treat or not to treat or what treatment to choose is really a key important factor in making this selection."

And he goes on:

"It strikes me that some patients might benefit from intervention, and we should identify those patients and maybe treat them a little earlier to improve their quality of life or give them some strategies to cope with the disease. And others may benefit from a different approach. Whether it's intervention or observation, trying to figure out who manages better based on the nature or the choice of intervention or just doing an intervention or not is really important and valuable and something that I think we need to focus more and more of our efforts on as we look at patients and think about what is the best way to approach their disease when they have many options."

And that's key. As patients, we do have options. The beginning of our lives as cancer patients is the worst time to make any kind of decisions. Our brains just aren't as rational as wed like them to be. So having a doctor take the time to lay things out for us is vital -- especially if we're in a place where the disease is stable and we don't need to make a decision immediately, as patients with more aggressive cancer have to do.

I do hope that researchers continue to pay attention to Quality of Life issues, both the physical ones and the emotional ones, and as a community, we continue to find ways to make it easier to live with the disease.

In some ways, I with that Dr. Leonard's #1 had been about a breakthrough treatment that would change it all for FL patients. That would always be ideal. But if that can't happen, and our best option to to find ways to live with the disease, then something like this works for me, too.

I'll keep reading and (I hope) finding times to share what I've learned with you. We're already moving toward the post-ASH write-ups of which research presentations generated the most excitement. I'll share those, too, when I see them.

FDA Investigation of CAR-T

Last week, the FDA announced that it was "investigating serious risk of T cell malignancy" in patients who have received CAR-T treatment. 

Obviously, any time the FDA issues a statement like that, it's worth looking into and being concerned about. But it's also worth noting that the statement also says that the benefits of CAR-T outweigh the risks. 

The statement from the FDA points out that they have received reports of CAR-T patients developing T cell cancers. In other words, the T cells that were manipulated as part of the treatment have become cancerous. Some of those patients then had to be hospitalized or died. This is alarming. Any treatment that results in death of the patient is problematic.

I realize that I'm walking a fine line with this post. I want to look at both sides of the issue but not minimize the problems that CAR-T might be creating. I'm also trying to stay positive, keeping in line with what I see the FDA statement as doing. 

The website Fierce Pharma has a good article on the FDA statement, providing a good bit of context. They provide some good numbers about CAR-T. Maybe most relevant is the data related to Kymriah and Yescarta, the two CAR-T treatments that can be used to treat some Follicular Lymphoma patients, and are the most-used CAR-T treatments (there are six in total). 

From those six versions of CAR-T, there have been 12 reported cases of T cell cancers. (I have seen elsewhere that it might be 19 cases). Ten of those 19 came from Kymriah and Yescarta patients. In statements from both of the manufacturers of these CAR-Ts, they pointed out that they are aware of the problem and are monitoring all of their patients (there have been over 27,000 patients who have received either Kymriah or Yescarta).

Again, I want to be clear that I know I am walking a fine line. 10 cases of T cell cancer out of 27,000 isn't many. But it's the entire world to those 10 patients. Even 1 more cancer in the world is 1 too many. And 12 (or 19) is enough to get the FDA concerned that more might be coming.

I've spent a week or so trying to find more context for all of this, and it's hard to find. One really good source, though, is the podcast Tumor Talk from Dr. Wes Wilson, a cancer researcher at the University of Pennsylvania. I'm having a hard time finding a good link to Tumor Talk, but you should be able to google the podcast name and find ways to access it through Twitter/X, which is how I found it.

Dr. Wilson points out that the FDA has not imposed any restrictions on CAR-T (which happens with some FDA warnings). Dr. Wilson also points out that CAR-T patients who received the treatments had already been heavily pre-treated, and so may have had weakened immune systems and been more susceptible to cancer. CAR-T can also suppress cells that fight cancer, making patients more susceptible. All of that said, he also has not heard of any UPenn patients (there have been over 100) who have developed T cell cancers. There are also several ways that T cells are created for CAR-T treatments, and it is possible (but not yet shown) that processes that were developed before FDA approval are the ones that have caused the problems -- that is presumably part of the FDA investigation. Finally, when the treatments were approved, one of the published potential side effects is the development of secondary cancers. That's true of many cancer treatments -- certainly true of traditional chemotherapy. Secondary cancers are common, unfortunately.

The question becomes one of risk tolerance. As Dr. Wilson says, CAR-T is still more beneficial than not receiving treatment. As of now, the data shows that the risk-benefit is "strongly weighted" toward getting the treatment. And it seems that many cancer hospitals are saying the same thing. And so is the FDA.

So what do I think about all of this? 

Who cares? I'm just a patient. The best person to talk to about this is your oncologist. Every cancer treatment has side effects, and thus come with risks. What's important is being aware of the possible treatments, how effective they might be for your situation, and how the potential side effects will affect your life, given your goals (are you looking for a cure? for long-term remission? for the least aggressive treatment that lets you maintain your quality of life?). Only you and your oncologist can answer those questions. 

In the meantime, I will certainly keep looking out for more news about this. (The FDA statement doesn't give a whole lot of detail, unfortunately.) If you are unfortunately in need of treatment soon, talk to your oncologist about all of your options, including CAR-T, and decide what's best for you.

Update on Epcoritamab

A quick update on Epcoritamab.

Epcoritamab is a bispecific antibody. I wrote about it less than 2 weeks ago in an ASH preview. I'm predicting that it will be the Follicular Lymphoma presentation that gets the most attention during and after the ASH conference.

Here's some attention before the conference as well:

The makers of Epcoritamab got some good news this week from the U.S. and from Europe.

The European Medicines Agency granted Epcoritamab a validation for a type 2 application for Relapsed/Refractory FL patients with at least two prior treatments.  The EMA is kind of European equivalent of the FDA, approving treatments before they are available to patients outside of clinical trials. A type 2 variance, as I understand it, includes things like expanding the use of an approved treatment. Epcoritamab was approved a few months ago as a treatment for R/R Diffuse Large B Cell Lymphoma.

In addition, the FDA has granted Breakthrough Therapy Designation for  Epcoritamab. This means that it will get a faster review than it would otherwise, because approval would mean a significant improvement in treatment options for patients with FL.

To be clear -- neither one of the agencies has granted a new approval for Epcoritamab for R/R Follicular Lymphoma. These are positive steps in the process. Both agencies will now take a closer look at the data, including the updated data to be presented at ASH, in determining whether or not to approve the treatment. 

That's good news for all of us. 

ASH Preview: Predicting POD24

I'm continuing my look at ASH abstracts, reading the summaries of the research on Follicular Lymphoma that will be presented at the conference in a few weeks. There is some really nice research happening. Nothing that is going to change things in a huge way. But lots of smaller, incremental progress, I think.

Two presentations showed up on my list next to each other. They both deal with predicting POD24. Lots of researchers have made this a priority. As you probably know, POD24 stands for Progression of Disease within 24 months. Research have found that FL patients who have successful immunochemotherapy (like R-CHOP or R-Bendamustine), but whose disease comes back or gets worse within 24 months, have a lower Overall Survival rate than other FL patients. POD24 was first proposed about 6 years ago from data in the GALLIUM study, and it affects about 20% of FL patients. It sometimes goes by other names like EFS24 (Event-Free Survival at 24 months). Slightly different, but essentially the same concept. 

Interestingly, the two ASH presentations that try to predict POD24 both try to build on the FLIPI model. 

I haven't written much about FLIPI lately, but it stands for Follicular Lymphoma International Prognostic Index.  FLIPI uses data like a patient's age, LDH levels, and disease stage to predict survival. It should NOT be used to determine an individual patient's survival, so if you are tempted to take the "quiz" that is linked above, do not panic if it gives you a bad outcome. It means nothing. As an example -- I just took the quiz and it gave me a 50/50 chance of surviving 10 years. I'll celebrate my 16th diagnosiversary in a couple of months.

FLIP is useless in predicting anything about an individual. It's far too general to do that, and it wasn't developed to do that. Instead, it was developed to help analyze clinical trial results, by giving FLIPI scores to participants so they could measure groups, not individuals. Treat FLIPI like a Buzzfeed quiz that predicts which Disney Princess you would be, because it's about as accurate in predicting your future. (That quiz said I was Tiana, when I'm obviously Belle, though Tiana is a pretty good second choice.)

There have been a lot of attempts to build on and refine FLIPI, adding more specific criteria that make more sense as predictors. A biomarker says a whole lot more about an individual's survival than their age. 

The two ASH presentations use refined FLIPI scores to try to predict POD24. They take very different approaches to developing them.

The first is presented in "1657: The FLIPI24 Prognostic Model Identifies Poor Outcomes in Non-Immunochemotherapy Treated Patients with Follicular Lymphoma." As I say above, POD24 involves FL patients who have received Imunochemotherapy.  This group of researchers is interested in FL patients who have progressed within 24 months who did not receive Immunochemotherapy, hoping to find a way to predict progression in that group of patients. They developed the FLIPI24 model to help them do that. The FLIPI24 measures some specific things -- age and LDH levels (both in the old FLIPI model), Hemoglobin (a protein that help carry oxygen in the blood), White Blood Cell counts, and B2M (a biomarker for a gene that is involved in cancer cell growth and survival). Their research looked at 1542 FL patients who had received different treatments like watching and waiting, straight Rituxan, and radiation (and a few more unspecified). 

The researchers found that their model did a good job of predicting EFS24 (Event Free Survival within 24 months). By grouping patients by risk, they were able to identify high risk patients, and this group had a median Event Free Survival of 1.8 years and a 5 year Overall Survival of just 65.1% (the whole group had a 5 year OS of about 90%). These smaller numbers held whether the patient had high or low tumor burden at diagnosis, and even if they were watching and waiting. In other words, clinical signs at diagnosis might have looked like the disease wasn't too aggressive, but the predictor model suggested otherwise. 

The second presentation took a very different approach. This one is called "3048: Development and Validation of a Machine-Learning Model to Predict POD24 Risk of Follicular Lymphoma."As the title suggests, this group of researchers used Artificial Intelligence (machine-learning) to develop their FLIPI variation, which they call FLIPI-C.  As I have written about before, I am very interested in AI and how it can help cancer patients. Still skeptical, but hopeful.

This group of researchers sued machine learning, a type of AI that can learn to develop algorithms, or ways of making decisions based on statistical patterns. One of the potential good things about AI is that it can look at things in ways that humans can't, because of our own biases, or because looking at the data would be expensive and time-consuming. That's what this group is doing with AI. (I'm being very generous here with AI's capabilities. As I said, I'm still skeptical.)

The researchers looked at 1938 patients with grade 3a Follicular Lymphoma. There are lots of statistics involved here, which is not my strength. But essentially, the researchers looked back at the FL patients and used the AI program to identify features that were common to the POD24 patients and then developed a new FLIPI model from there. They compared their model to other FLIPI variations. 

Interestingly, there is some overlap with the FLIPI24 model above, like measuring LDH, Hemoglobin, and B2M, but also includes things like comparing some white blood cell levels and several more involving lymph nodes (not much detail in a summary of just a few hundred words -- it will be interesting to see all of it laid out in a journal article some day).

What I find most interesting about the two studies is the overlap. They came at them from different directions, and came to some of the same conclusions. That gives me some hope that an improved FLIPI model could help. I'll be very interested to see if anyone does a more thorough job of comparing these two presentations in one of the many commentaries that will come out in the next few months.

Whatever the case, I'm pleased that there is continued effort to figure out early on which FL patients are likely to be POD24. That might mean more aggressive treatment early, or more careful observation, or ideally, the development of new treatments based on newly discovered biomarkers. Some kind if help for this vulnerable group would be wonderful.

I'll keep reading and sharing. Stay tuned.

ASH Preview: Epcoritamab (Bispecific)

OK, enough about skin cancer. This is supposed to be a blog about Follicular Lymphoma. 

So let's get back to the ASH convention and what is coming up there.

It's always interesting to guess which FL presentations at conferences (if any) are going to get lots of attention by the oncology community. Occasionally, there are some blockbusters that change the way FL patients are treated (like when R-Squared trial results were announced). Most years, there isn't much that generates a lot of excitement on sites like OncLive that cover cancer news.

If I had to guess which presentation will get some attention this year, it will be this one: 1655 Epcoritamab SC Monotherapy Leads to Deep and Durable Responses in Patients with Relapsed or Refractory Follicular Lymphoma: First Data Disclosure from the Epcore NHL-1 Follicular Lymphoma Dose-Expansion Cohort. 

Epcoritamab is a bispecific antibody. To remind you of what that means -- a bispecific antibody works sort of like a monoclonal antibody like Rituxan. It targets a protein on the surface of the cancer cell. In fact, Epcoritamab targets the same prtein that Rituxan targets -- CD20. But a bispecific has a second part to it ("bi" in "bispecific" means "two," so two parts to it). The second part targets the protein CD3 on T cells, a kind of immune cell. So by bringing the cancer cell in close contact with an immune cell, the bispecific helps to eliminate the cancer cell. 

There is already a bispecific approved by the FDA for FL -- Mosunetuzumab (for patients with relapsed/refractory disease who have had at least 2 treatments). Another (Odronextromab) has received priority review from the FDA. And Epcoritamab has been pretty successful, too. It has been approved in the US and UK for r/r Diffuse Large B Cell Lymphoma. And at the ASCO conference last June, some results were shared that showed a successful pairing of Epcoritamab and R-Squared. 

This research at ASH focuses on single use Epcoritamab, tested in a phase 1/2 clinical trial. It's a fairly large trial for one that is early -- 128 patients with r/r FL who have had at least 2 prior treatments. The ASH abstract makes clear that the hope is to show that Epcoritamab can work for as many patients as possible. They point out all of the different prior treatment types that patients had received -- 77% had anthracyclines (like R-CHOP), 31% had Lenalidomide, 19% had a stem cell transplant. 

Most patients (54%) were primary refractory (they never had a Complete Response to a treatment), 70% were double refractory (two treatments didn't work), and 69% were refractory to their last treatment. In addition, 42% were POD24 (their disease returned within 24 months of receiving immuno-chemotherapy). So, in short, this is a group of patients that could really use a good option.

Results were very good.  The Overall Response Rate was 82%, with a Complete Response Rate of 63%. (For the sake of comparison, the phase 2 trial that led to Mosunetuzumab's approval showed an 80% ORR and a 60% CR). More importantly, the response rates were pretty consistent across high-risk subgroups -- double refractory patients had an ORR of 76% and a CR of 56%, POD24 were 80% and 60%, etc. Patients who had 2 prior treatments had response rates of 89% and 72%; 3 prior treatments were 88% and 68%; 4 or more prior treatments were 68% and 45%.

As for safety (the most important thing being considered in a phase 1 trial), the most common side effects were Cytokine Release Syndrome (66%), injection-site reaction (57%), COVID-19 (40%), fatigue (30%), low white blood cell counts (28%), diarrhea (27%), and fever (25%). Side effects leading to stopping treatment happened to 19% of patients, the most commonly because of COVID-19. Side effects were mostly low grade.

(It's worth noting that the data here is from patients treated from  2020 to 2022, at the height of Covid. It makes sense that a treatment that compromises the immune system would result in such a high number of people stopping treatment. This is the first time I've seen Covid mentioned this way in a trial write-up.)

So overall, this is very good news. It's still a very early trial. I don't imagine an application for approval will come until there is more data (the FDA is being more careful about these things lately), but it's good news. And since bispecifics are one of the treatment types that gets oncologists most excited these days (along with CAR-T), I'm guessing it will be included in news stories and summaries about the best things that happened at the conference.

I'll try to pick out a few more gems from the abstract list. The conference is coming up pretty soon -- just a few more weeks. I'll see how much reading I can do before then.

Skin Cancer Surgery

 A quick update -- I had my skin cancer surgery yesterday. It all went fine.

As you might remember, I was diagnosed a few weeks ago with Basal Cell Carcinoma on the top of my head. Basal Cell Carcinoma is the most frequently diagnosed cancer in the United States. It is generally not very aggressive, though if it goes untreated, it can cause problems. Mine was caught pretty quickly (I see my dermatologist every 6 months for this exact reason).

I've written about this before, but my skin cancer likely came because of a combination of things -- my own carelessness when I was young, leading to multiple bad sunburns, plus having a cancer of the immune system, plus getting a treatment that messes with my immune system. That perfect storm of factors probably all contributed to the cancer. It happens to about 1 in 10 FL patients, roughly.

So, as far as the surgery goes, it was both fast and slow. The fast part was the actual surgery. I had the basal cell carcinoma removed with Mohs Surgery, which is common for skin cancers. Basically, the surgeon removes a thin layer of skin, and then checks it for cancer cells. If there are cells present, then they remove another layer and check that. And they keep going until there are no more cancer cells present. It's an effective and less-invasive surgery than some others, since they are able to work on only the areas that have cancer cells present.

So the incising part was fast -- maybe 5 minutes. But then came the slow part -- bring the sample to an in-house lab and going through the process of finding the cancer cells. That took about 90 minutes. They told me to bring a lunch and something to keep me occupied, since it could take a while if I had multiple layers to remove. I brought some work with me, thinking I'd be productive. But I ended up in the regular waiting room, which wasn't too conducive to the work I had brought. So I did some reading instead. The time passed OK.

After the first round, the surgeon said there was one more area with cancer cells, but he was confident that he could get them all on one shot. So he did some more work, then stitched me up and sent me home. He said if he found more cancer (which he didn't think was likely), he'd let me know. I didn't get a call within a couple of hours, so I'm clear.

I've had a little bit of pain, but nothing that some Tylenol hasn't taken care of. So it hasn't been too horrible an experience. Cancer is always serious, and surgery is never fun. But I'm doing OK. I did that work I had hoped to do when I got home.

It was, in the end, a fairly small incision, covered by a fairly big bandage:

So, as always, the lesson here is -- take care of yourself. Go to your doctor appointments. Do whatever tests and preventative and diagnostic procedures that you are supposed to. I know those of you reading are cancer patients and caregivers -- you take this stuff seriously. Remind the people that you love and make sure they take it seriously, too.

Take care, everyone. More soon on that other cancer that we are all so interested in.

Goodbye to the Last PI3K Inhibitor

Well, the last of the several PI3K Inhibitors for Follicular Lymphoma is no more. The manufacturer of Copanlisib voluntarily pulled it off of the market yesterday.

It's been a while since I wrote about the sad saga of PI3K inhibitors for FL. They showed lots of promise in early trials. They work by inhibiting, or stopping, an enzyme called PI3K, or Phosphatidylinositol 3-kinase. PI3K is a part of a chain of enzymes and proteins that turn switches on and off in a cell that allow the cell to grow and live. So when one part of that chain has a problem, the cell refuses to die which is what cancer is -- a bunch of cells that refuse to die. A PI3K inhibitor stops that process so the cell can die as it is supposed to, after doing its job. 

And the PI3K inhibitors that were tested and approved did a pretty good job of stopping the things they were supposed to stop. But they ran into a bunch of other problems, too. One of them was safety. Side effects were more severe than expected, including some related to digestion. (One reason Copanlisib may have lasted as long as it did was because it was intravenous, rather then the once-a-day pill like the others. There was some speculation that helped Copanlisib bypass the stomach issues.) But another trial also found that there was a slightly higher risk of death among patients taking the inhibitor than there was in a comparison group. Not good at all.

I've written a lot about these in the past, so if you want to read more, you can go to this post, and then look for the links to take you to previous posts about the individual inhibitors and the problems they had.)

It seems to me that a lot of the problems with PI3K inhibitors came from the accelerated approvals they got from the FDA. (And as I give you this opinion, I will remind you yet again that I am not an oncologist, or a cancer researcher, or a pharma or FDA employee, or anyone else who is trained to know about these things. I'm just a cancer patient who reads a lot.)

The problem with the accelerated approvals was that, like all accelerated approvals, they were based on small phase 2 clinical trial results. The approval allowed the developers to start marketing the treatment, with the idea that a larger phase 3 trial was necessary for final approval. Those results were mixed. Copanlisib, for example, says that their phase 3 trial did not meet its primary endpoint -- the results did not show what they had hoped to show. No more details than that, but that's the issue.

Another problem, it seems to me, was that there were so many PI3K inhibitors developed at once. They were all slightly different -- different enough that the FDA approved them all.  But in practical terms, they were all competing for patients to join their phase 3 trials.  So a couple of them voluntarily pulled their inhibitor from the market because they couldn't get enough patients. The pandemic was a factor there, too, but having so much competition couldn't have helped.

With Copanlisib being withdrawn, that looks like the end for PI3K inhibitors for Follicular Lymphoma. I suppose it's possible that someone could try to develop a new one, or improve upon those that already exist, or keep trying them in combination with other treatments. But with the amount of time and money that goes into research, testing, and marketing for a new treatment, that doesn't seem likely to me.

Which is a real shame. PI3K inhibitors were one of those treatments that got oncologists really excited, based on early trial results. I always hate to see a treatment option be taken off the table.

I try to take hope in knowing that there are a bunch more treatments in the pipeline. Not all of them will get past stage 1 or stage 2 trials. Some of them might end up like these above, with early promise that's never fulfilled. But maybe a few will be available to us in the next few years.

All the more reason to get to those ASH abstracts.....  

ASH Abstracts (and Watching and Waiting)

 ASH Abstracts are here!

For those of you who are newer to this, ASH is the American Society of Hematology, a large group of blood disease specialists (including blood cancers like Follicular Lymphoma). Every year, they have a big meeting, usually in early December. This year it will be held December 9-12.

And about a month or so before the meeting, they release their abstracts -- the summaries of the presentations that researchers will make at the meeting. (The abstracts are available to view online.) The presentation might be about new research or clinical trial results (my favorite), or research that looks more closely at already available treatments (also very interesting), or research done on topics like survivorship, diet and exercise, or other topics related to blood cancers. 

I read as many of them as I can, and try to talk about some of the interesting ones here. 

I'm already getting emails about the research that will be presented. The makers of Yescarta (or Axi-cel), a CAR-T treatment, are planning to present a whole bunch of updated research results at ASH, according to a press release I got today.

My quick look at the abstracts tells me that there should be a whole lot of good things to share this year. I haven't looked deeply enough to know if there will be a game-changer for FL, but I'll keep my eyes open.

I'll share a quick one, though, that I found interesting -- abstract #4417: Time to Lymphoma Treatment within 24 Months in Watchful Waiting Follicular Lymphoma Defines Patients at High Risk for Progression: A Multicenter Analysis.

As someone who watched and waited (for 2 years, to the day!) before getting treatment, any research on W & W always catches my eye. This presentation looks at 411 FL patients diagnosed between 2008 and 2022, who watched and waited until they needed treatment. the researchers are interested in whether TLT (Time to Lymphoma Treatment -- the amount of time between diagnosis and treatment) affected survival outcomes.

They found that patients who needed treatment within 24 months of beginning watch and wait had lower 5 year Progression Free Survival. The 5 year PFS for the TLT24 group (as they are calling it) was 62.3%, while the 5 year PFS for those who didn't need treatment within 24 months was 89.5%. The researchers developed a model that uses clinical and laboratory factors to identify patients at high risk for TLT24, and recommend that those patients get early treatment instead of continuing to watch and wait.

This is one of those presentations that make we wish I had more information. My ears kind of perk up a little at this, given that the time period covered begins right when I was diagnosed (in January 2008) and includes information that involves me (I was TLT24 myself, apparently). Looking back, i am firmly in the 62.3% that had a good 5 year PFS. It makes me a little defensive.

But then I step back and put on scientist hat (remember, I'm not an actual scientist, so I have dress up like one). And I remember that statistics look at a large group of people reduced to numbers, not at individual patients. 

I'd still like to know more about the patients in the study, and how many of them had factors that put them at greater risk already. And I have to remind myself that this research is not a criticism of watching and waiting -- no one is saying that the W and W caused the problem (I do see research that seems to imply that every now and then).

No, it's a good thing -- an attempt to find out early on whether watching and waiting is a good option for people. If we knew that, it might help with the emotional decision that a lot of people have to make. I know very well what a weird thing it is to have a doctor say "You have cancer, but we're not actually going to treat it." Being able to say "Based o these factors, you're at a lower risk, so we can wait" might be a great thing. And so might, "Based on these factors, even though you're asymptomatic, we think you should get treatment now and potentially avoid problems later." It's one more factor to help patients make a decision.

So that was a good one right off the bat. I'm sure there will be some more interesting research to come.

Stay tuned.

Options for Relapsed/Refractory FL (Videos)

Cancer Network has recently added to their video series called "Growing Options for R/R Follicular Lymphoma."

The series features several short videos of a conversation between four Lymphoma specialists: Dr. Brian Hill of the Cleveland Clinic; Jennifer Garson, a physician assistant at Rush University Cancer Center; Dr. Muhamad Alhaj Moustafa of the Mayo Clinic; and Dr. Tycel Phillips of the City of Hope Cancer Center.

The series actually begins with a written interview (not a video) with Ms. Garson, who talks about dealing with some of the side effects of treatment. Episode 2, the first video, introduces the speakers and focuses briefly on the evolution of treating FL, with each participant talking about how the field has changed. Ms. Garson, for example, talks about Rituxan and the ways it changed treatment and improved Overall Survival. Dr. Moustafa talks about the changes from the last 5 years or so, with the introduction of treatments like R-squared and bi-specifics. Dr. Phillips adds CAR-T to the list, and says he is "excited to see where things are going."

(I will add that one of the reasons I like video series like this is for just what Dr. Phillips says. It's always great to see Lymphoma experts get excited about the work they do and what we might see in the future.)

Episode 3 looks more specifically at a case study -- a 65 year old woman with Follicular Lymphoma. Dr. Hill goes through her symptoms (some of them will sound familiar!), and her diagnosis of stage 4 grade 3A FL, and the panel suggests what they might have done if they had seen this patient. 

I enjoy this kind of thing, too. I'm not a doctor -- it's been a little bit since I have reminded you all about that -- but I like to guess what the doctor may have suggested. I guessed R-squared for a first treatment -- a cancer that's not too aggressive, but chemo seems old-fashioned for this group. And then CAR-T or a bi-specific if it returned. 

And I was wrong. The actual patient was given Bendamustine and Rituxan, which Dr. Moustafa called "the standard of care right now" (which is probably accurate). They debated whether or not R-CHOP would be appropriate, if it had been more aggressive on the PET scan, and transformation was a possibility.

Then they asked about what to do next, and they debated R-Maintenance, which they agreed was controversial and appropriate for some, but not all, patients. (Part of that decision has to do with the pandemic, and being more careful about messing with patients' immune systems. It has apparently changed quite a bit since the pandemic, with more oncologists being cautious with Maintenance.)

And if the FL returned? In the case study, the patient relapsed after 4 years, with grade1/2 FL coming back. They had several possibilities -- one chose R-Squared (or maybe Revlimid with Obinutuzumab instead of Rituxan). They wanted to hold off on R-CHOP until it was needed for transformation. Other possibilities were plain Rituxan or possible pathway inhibitors, though they are usually used for a 3rd round of treatment, or a clinical trial.

The lesson here, everyone? Be glad that I'm not your doctor. I'd probably get your treatment plan wrong. 

They do also talk about CAR-T, though they thought this was a fairly aggressive treatment, as was Stem Cell Transplant, and bi-specifics. Some of those would probably come later, as a 3rd or 4th line of treatment. Additional videos talk about some of these other options. You can find all of them on the page linked above.

It's very interesting to me that the doctors in this series were much more conservative than I had guessed they would be. Reading so much about newer treatments, it's easy to get caught  up in the excitement about them. But when it comes to actual doctors treating actual patients, the tried-and-true treatments, the ones that they know will actually work, are the ones that they recommend. The newer, more exciting stuff comes later on, when they patient has fewer options.

Change comes slowly in lots of places, including oncology. I don't think that's a bad thing. There's a big difference between getting excited about bi-specifics at a conference with other oncologists, and deciding whether to recommend a treatment that was approved just a few months ago to a scared patient who is sitting in your exam room. The conservative approach makes a lot of sense to me (and, to be honest, was the approach my own oncologist took, and which I happily agreed to.)

The series continues with more discussions of newer treatments, and then with a return to the case study of the 65 year old woman who had B-R. But this time they imagined that she didn't get a 4 year remission. Instead, it was only 4 months.  That makes her POD24 -- immunochemotherapy that stopped working within 24 months. These patients have a much lower median OS. What to do?

I won't share what my guess is with this one, or whether it lined up with what the doctors on the panel recommended. 

But I will say that the whole series was a great reminder that a laptop isn't a treatment room, and a patient-blogger isn't an oncologist. Remember that -- the best source of information about Follicular Lymphoma, and how it affects you as a patient, is your own doctor.

Understanding the Immune System

I've been going back into my files, looking at some of the older things that I set aside to look at later. Well, it's later now. Here's an interesting piece published about a month ago on OncLive.

It's an interview with Dr. Stephen Ansell from the Mayo Clinic in Minnesota, who talks about the challenges of understanding the immune system, and how greater understanding might lead to better lymphoma treatments. The interview is based on a presentation he made at the SOHO (Society of Hematologic Oncology) meeting in September.

As Dr. Ansell points out, the immune system is very complex. There are several different immune cells, and they serve different functions, targeting different invaders, working in sequence or together to fight infection. While we know the basics of how those cells work, we're only really just beginning to understand how to harness their power to treat cancer. You can see their promise when you think about the two types of treatments that get Lymphoma experts most excited right now -- CAR-T (which changes immune cells in a lab so they can detect cancer cells) and bispecifics (which bring immune cells into close contact with cancer cells). 

So when you consider that those treatments have been very effective, but not completely effective, one question to ask is, when they stop working, is it because of some issue with our not understanding completely how immune cells work? In other words, if CAR-T works well and gets a Complete Response, but then stops working, what changed? In theory, T cells have a memory -- once they encounter their target, they will remember it for the next time it shows up. So what happens with refractory CAR-T (when it worked but then stopped working)? Do they stop remembering? Did they change in some way? Those are the kinds of questions that need to be answered.

And, of course, there are questions that go beyond CAR-T and bispecifics, which target CD 19 and CD20 proteins on cancer cells. Another type of treatment being developed uses a different kind of immune cell called a macrophage, even more powerful than T cells. Macrophages can target yet another protein, CD47.

Then there is the question of treatment sequencing. If certain treatments are given after others stop working, do they have a negative effect on the immune system, in ways that prevent other immune-cell-based treatments from working effectively? In other words, if chemo messes with the immune system, will that make CAR-T less effective later on, because it involves the immune cells that need to be changed to find the cancer cells?

And what about treatment combinations? Would adding, say, Rituxan to another immunotherapy create problems? There's always the danger of increased side effects with combining treatments. But will one of those side effects be lessening the effectiveness of the immune cells that are being used to treat the cancer?

I find it all very fascinating. I always thought, way back in school, that the immune system was interesting. I thought it was strange that we had this kind of second blood system, the lymphatic system, that no one ever talked about. Now here I am with Lymphoma. Isn't life funny?

But I do find it all fascinating, and I'm glad that lots of researchers do, too.  I'm sure we'll see lots of improvements to current treatments, and maybe some new treatments, coming out of all of this research in the next few years.

Minimal Residual Disease and Cancer Blood Tests

 I' have two related things that I want to talk about. One's been sitting in my email inbox for a while, and the other has been sitting on my kitchen table. They both have to do with blood testing as a way to detect cancer.

The thing in my email is a story from MedPage Today called "Final Results From PATHFINDER Study of GRAIL’s Multi-Cancer Early Detection Blood Test Published in The Lancet." This one is very cool. It describes the clinical trial results for a blood test called Galleri, which may be used to detect multiple cancers, possibly while they are asymptomatic. It's the "multiple" part that is getting people very excited. From a simple blood sample, the test can detect whether or not the patient has one (or more) of several cancers. The results look very promising, especially since about half of the patients that the blood test found potential cancer in detected the cancer at stage 1 or 2, when treatment is likely to be more effective. Another promising statistic -- 74% of the cancers found were for cancers that do not have a recommended screening (the way something like breast or colon cancer has a recommended screening). 

It's not a perfect test, but it's good enough that it could be very valuable for early detection for a lot of people. It's really a first step -- signalling that something should be checked out more carefully with other testing. It's less invasive that a lot of other tests might be.

The other thing that I read recently is an article from CURE magazine. It's called "On the Lookout for Minimal Residual Disease in Leukemia." It has a similar theme -- a blood test can help detect "minimal residual disease" after treatment for blood cancer. In other words, a patient might seem to have their cancer completely cured because a PET scan isn't picking up any cancer cells. But the blood test can pick up tiny amounts of cancer that a PET scan can't, letting the doctor know that a little more "salvage" treatment might be necessary. It could take months or years for the little bit of leftover cancer to show up on a scan, so the test can find it while it is still more manageable.

Both of these items highlight the kind of "liquid biopsies" that have been making a lot of noise lately. They both work on the same principle -- they can find changes in DNA in cells that send a signal that something isn't right. 

It's kind of amazing that we're able to look at such small pieces of ourselves, and it reminds me of how far we've come in a fairly short time. I remember my own biopsy. I had surgery under general anesthesia so the surgeon could remove a lymph node in my hip for testing. I was limping for a week. (I went into work the next day even though I wasn't supposed to.) The sample went to a lab, where it was looked at under a microscope  and determined to be Follicular Lymphoma. So in some sense it was worth the trouble. But if it had come back negative, that would have been unnecessary invasive surgery.

Now, this isn't to say that a liquid biopsy would completely eliminate the need for a physical biopsy. I don't think we're there yet. Someone who took the blood test and got a result for, say, pancreatic cancer might still need a scan and a biopsy to determine what was really going on. But the test has the potential to catch that cancer early. That's a wonderful thing.

My guess is we'll be seeing more research results in the next few years for MRD testing and liquid biopsies in FL. Some might be describing new tests, some might be testing what already exists. But the technology seems to be getting better all the time. Particularly for post-treatment testing, it seems likely to be a part of our testing kit in the very near future.

Good stuff.

LRF Educational Programs

As I've done in the past, I'd like to alert you all about some upcoming webinars and educational programs presented by the Lymphoma Research Foundation. I have found them very helpful, and I hope they may be helpful for some of you, too.

One of the most interesting programs that the LRF offers is their "Ask the Doctor" series. This is just what it sounds like -- the chance to hear briefly from a Lymphoma expert and then ask specific questions. At one time (pre-Covid), the LRF held in-person sessions. I went to one of them near me a few years ago. But I think they might all be online now. These are not recorded, so if you're interested, you have to tune in live.

There are four "Ask the Doctor" sessions coming up in the next few months:

• Ask the Doctor About Lymphoma: Information for Newly Diagnosed Patients – October 19, 2023, featuring Dr. Tanaya Shree of Oregon Health and Sciences University
• Ask the Doctor About Lymphoma: Information for Relapsed/Refractory Patients – November 16, 2023, featuring Dr. Ayushi Chauhan of Augusta University Health
• Ask the Doctor About Lymphoma: Information on Treatment Options and Clinical Trials – December 5, 2023, featuring Dr. Christine Ryan of the Dana-Farber Cancer Institute
• And finally, a program in Spanish: Pregunte al doctor sobre el linfoma – 21 de diciembre del 2023.
  Presentador: Dr. Jorge Castillo, Dana-Farber Cancer Institute

Clicking on those links will take you to the LRF we page for each of the webinars, where you can register.

the LRF is also offering a national virtual program called "Lymphoma Workshop: Understanding Lymphoma Basics and Current Treatment Options" on Saturday, November 4, 2023. this is an all-day workshop, from 9:30am to 3:00pm EST. There are a whole bunch of presenters for this, with a few sessions for specific Lymphoma subtypes. A few particular sessions look especially interesting.

The first is a session on Follicular Lymphoma and Marginal Zone Lymphoma from Dr. Thomas Habermann from the Mayo Clinic.I'm sure there will be some nice updates on newer treatments.

The other that looks great to me is called "Lymphoma Survivorship" with Dr. Carrie Thompson, also fro the Mayo Clinic. I've heard her speak before on Survivorship, and I follow her on Twitter/X. I think she's great, and her research is on survivorship and life after treatment. Should be a good one.

Of course, all of these are free.

I like LRF's programs because they usually feature some very good doctors and researchers who know exactly what is happening in the world of Lymphoma. But at the same time, they also know how to explain things in language that patients can understand. It's a rare combination in a doctor.

I hope some of you get a chance to attend. And if not, remember that a lot of LRF's programs are archived and available to watch any time.

Enjoy.

Skin Cancer Diagnosis

Well, folks, it's official -- I have a secondary cancer.

I went to my dermatologist about a week ago, and she biopsied a growth on my scalp. Results came back a couple of days ago, and it's Basal Cell Carcinoma. 

And, in my mind, it's not too big a deal. 

For one thing, I've been kind of preparing emotionally for this for about two years. My current oncologist has been encouraging me to go to the dermatologist for at least that long, reminding me that as a Follicular Lymphoma patient, I am at greater risk of skin cancer than most people. FL, as you know, is a cancer of B cells, a type of immune cells, which makes my immune system a little bit more "special" than others'. And since the treatment I received has a way of messing even more with the immune system  (this is true of pretty much every FL treatment), it's no surprise that I have had some cells behaving in ways they shouldn't. And misbehaving cells can lead to cancer.

It's also not a surprise because I grew up at a time when sunscreen just wasn't a thing. I had regular sunburns as a kid -- red skin, blisters, peeling, can't-sleep-because-the-sheets-hurt-when-they-touch-your-skin kinds of sunburns. In fact, I was about 22 when I last got one of those. I should have known better by that point, but it was the summer before I met my wife and I was still a self-destructive jerk. She changed me for the better. My point is, that combination of funky immune system and a history of sun damage makes for perfect conditions for skin cancer.

It was almost exactly a year ago when I wrote about my last close call with skin cancer. My dermatologist did a biopsy then, too, fearing I had a different type of skin cancer -- squamous cell. That one turned out to be negative, removed just before it was likely to turn cancerous. This one wasn't so quick. 

The good news is that Basal Cell Carcinoma is the most common type of cancer in the USA, with about 3.6 million diagnoses every year (according to The Skin Cancer Foundation). It is non-aggressive, and as long as it is treated soon, it shouldn't cause any major problems.

I'm scheduled for surgery in about a month -- no hurry, no worries. It will be in an-office procedure with a local anesthetic. I'll write more about it after it happens. If I was 40 years younger, I'd document the whole thing on Instagram. I probably won't do that.

The lesson here, as I said a year ago -- pay attention to your body and do any scheduled cancer screenings that your doctor recommends. Colonoscopy, breast or prostate exams, skin tests -- all of it.

I think most of us FL patients are probably aware of our own bodies, and we know when something isn't right. That's the "blessing" of having a slow-growing, incurable cancer. We pay attention. But I also know that many cancer patients finish treatment and then just don't want to think about it anymore. I get that. But make sure there is a balance. Don't think about cancer for 364 days of the year. For the other day, get whatever prevention and detection tests are available.

And remember to urge your family and friends to do the same. Tell them your story. Embellish it if you have to. I'm all in favor of shame, guilt, and fear if it gets someone to the doctor's office for a cancer screening.

I'll keep you all updated. Probably won't be much to tell, which is how I like it.

Stay well. Get checked.

FDA Priority Review for Odronextamab

Big news in the Lymphoma community -- the FDA has granted Priority Review for Odronextamab.  It's being reported on most of the major oncology news sites. 

Odronextamab is a CD20 x CD3 bi-specific.  As a reminder, a bispecific works like a monoclonal antibody like Rituxan by seeking out a protein on the surface of a B cell called CD20 (just like Rituxan). But it also targets the CD3 protein on T cells, a type of immune cell that will be floating in the blood along with the B cells. A bi-specific will attach to both and bring the T cell in contact with the cancerous B cell and help the immune cell to eliminate it. Right now, the only bi-specific available to Follicular Lymphoma patients is Mosunetuzumab.

The Priority Review is based on phase 1 and phase 2 clinical trial results. I first started writing about Odronextamab about four years ago, when it was still known as REGN1979. The application is for both Relapsed/Refractory FL and DLBCL (that is, the patient's last treatment stopped working or did not work at all). Patients need to have had at least two previous treatments.

Results have been very good. In the phase 2 trial, patients with Follicular Lymphoma had an Overall Response of 82% and a Complete Response of 75%. The median duration of response was 20.5 months and the median Progression Free Survival was 20 months.

As for safety, 100% of the 131 patients with FL experienced side effects (which isn't surprising -- all cancer treatments result in side effects), and 78% of them experienced grade 3 Adverse Events (more serious side effects). The most common side effects were Cytokine Release Syndrome (over half of patients), low blood cell counts, diarrhea, fever, joint pain, and infusion-related reactions. None of the CRS were grade 4 or 5, which are the most serious.

So it seems like the side effects are manageable. 

If you've been reading for a while, you know that bi-specifics (along with CAR-T) are the Lymphoma treatments that get oncologists most excited. Given some of the issues that Lymphoma treatments have been having in the last few years, I would expect a very thorough vetting by the FDA. The target date for a decision by the FDA is March 31, 2024. I wouldn't be surprised if we saw some updated trial results at ASH in a few months; the last time any results were presented was at last year's ASH. And I would expect it to be positive (maybe updated numbers on duration of response).

Definitely one to keep an eye on.

Thanks a Million!

I have some very cool news to share with you all.

The Lympho Bob blog has reached 1 million total page views!

I didn't catch the exact moment that it happened, but this was the page view counter that showed it to me:

 

So, a great big thank you to all of you have read the blog. An especially big thank you to those of you who have been reading for years.

I've told the story of this blog before, but I'll tell it again. I started the blog very soon after I was diagnosed. It was a way to tell family and friends what was happening with my diagnosis, any testing, and any possible treatment. I know from experience how people react when someone else has cancer -- they want to know what's happening, but they don't want to call and ask and feel like they are being a bother. I wanted people to know what was happening with me, so I tried to make it easy. They could just google "Lympho Bob" and read all they wanted, and maybe leave a comment.

And people did leave comments. And they meant a lot in those early days. As I'm sure many of you know, even a little acknowledgement of what you are going through can mean a lot. 

I also used the blog to let people know how I was feeling every day. Most days, that meant telling people I felt good. So if you're wondering why I have a picture of the singer James Brown in my profile, that's why -- his song "I Got You" has the famous line, "I feel good."

Over time, because I was watching and waiting, I kind of ran out of things to write about, regarding my own cancer. My oncologist appointments were less frequent and I had much less news to share. The blog became a kind of gathering place for some family members, and for a while I wrote about a lot more non-cancer topics. And then came Facebook. As a family member told me back then, Facebook gave everyone a new place to gather online, so they stopped coming to my blog.

No problem. At that time, I was reading and writing more about Follicular Lymphoma research. And pretty soon, I started to get comments from people I had never met. And that was really cool. And then at some point, I got a comment from someone overseas. And that was even cooler.

And all of this time, I didn't really know exactly how many people were actually reading the blog. At some point, Google (which owns Blogger, my hosting platform) added a counter and some widgets, and I was able to see just how many people were actually reading the blog. And that was very, very cool.

So where am I now with the blog? Let me share a few numbers.

• I have readers from at least 82 countries, from Argentina to Yemen and many places in between. Blogger doesn't tell me anything about who exactly is reading an individual post, but it does tell me things like how many readers I had from each country for the last week, and which browser they used. So I kind of kept a running list for a while to come up with the 82 different countries. It's fun to look at.
• This post is the 1738th that I have published. I try to post once or twice a week. Once per week is more likely these days, with my schedule.
• This is not the 1738th post I have written, however. I have about 300 more drafts in my folder on Blogger that I started but never published, and probably another 500 that I didn't bother to save. That happens a lot. I'll find something online that seems really interesting and I'll save a draft with a link, and then I'll go back and read it and find that it wasn't all that interesting anymore and I'll never write or publish the post. Other times, I'll find an article in a medical journal, usually something with a lot of science or statistics, that will seem really important. But then as I'm writing, there will be parts of it that I just don't understand, and even with some research, I can't understand it well enough to explain it to you. If I can't explain it, I don't publish it. Like I said, that happens a lot. 
• I probably spend anywhere from 1 to 4 hours per post, between searching for ideas, watching videos, writing things up, researching any information I need, and editing. Some days I just don't have the time, but if I'm getting close to a week between posts, I'll find the inspiration to write something.
  

A lot of the blog has stayed the same since I started it. I resist some "best practices" -- the advice that blog writers get for how to be up-to-date. I am very aware of that advice, but for the most part, I don't make the changes that are recommended. The layout has stayed the same the whole time, even though Blogger offers lots of choices for a more modern look. The banner at the top is still lime green, the color of lymphoma awareness ribbons. I don't use a lot of images, because I have seen some blogs that use them for no real purpose. If it adds something to a post, I'll include a photo. They would help the blog become more visible to search engines, but they also slow things down for a lot of readers. I like that the look of the blog has stayed the same all these years -- simple, with a focus on the words. If you go away for a while and then come back, you know you're in the right place.

I've never had ads in the blog. When I first started writing, internet ads were kind of crude. By that I mean, if you searched for shoes, you'd get an ad about shoes. So 15 years ago, when I searched for information about cancer, I'd get ads for life insurance and funeral homes. I just didn't want those things on my blog, and if I added advertisements, that's what they would have been. Ads are much more sophisticated now, and use a whole lot of information to tailor advertisements to each individual. But I'd still want more control over which ads were shown on the blog. I could make a little money with ads, but to me, it's just not worth it. I'm lucky to have a good job that I love. I can live without the ad revenue.

I also have never collected personal information from readers. I don't have an email list, and I don't use any cookies (though Blogger might use some cookies that I don't have any control over). If you don't leave me a comment or send me an email, I have no idea who you are. I like it that way. I'm always happy to answer an email, whether it's someone asking for advice, or for help understanding something, or just saying hello and thank you. (In real life, I'm a teacher. I'm always happy to help another patient.) But I also know that we all handle our cancer in the way that makes most sense to us. For some, it's being very public. For others, it's being more private. So if you like to read the blog and leave it at that, then that's great. Use it in whatever way that makes most sense for you. I'll never demand to know who you are.

There are days when it's hard to write, and sometimes long stretches when I can't find much to say. But it seems like whenever that happens, I'll get a comment or an email that says something nice and keeps me going. Keep doing that if you are so inclined. It's all the payment I need.

So whether you've only read a handful of posts, or you've read all 1738 of them, thank you so much for reading. As long as there's someone reading, I'll keep writing.

Stay well.

European Approval Application for Odronextamab

I'm about a month late with this news, but the makers of the bi-specific Odronextamab applied for approval with the European Medicines Agency (EMA) in August.

As I've said before, I'm trying to pay more attention to what's happening with Follicular Lymphoma outside of the USA, since so many of my readers are from other parts of the world. And since Odronextamab is a bi-specific, one of the more exciting types of treatments available to FL patients, it's definitely news worth sharing. 

Odronextamab had already been given Orphan Designation by the EMA. "Orphan Designation" is a particular program for the EMA (the FDA has something very similar). It's a program that focuses on treatments for rare diseases, and provides incentives for manufacturers to develop these treatments. It makes sense -- if a drug maker can use it's time and resources for a treatment for high blood pressure or diabetes, something that affects millions of people, they can make billions of dollars every year on an effective treatment. But that means there is little incentive to spend those same resources on a treatment for a rare disease that might only affect a few thousand people every year. Orphan Designation gives them a reason to focus on those potentially less profitable diseases. 

So after Odronextamab got the Orphan Designation and went through some trials, they had good results. As a bi-specific, the treatment targets the CD20 protein on a cancer cell and the CD3 protein on a T cell (an immune cell) and brings them together so the immune cell can take out the cancer cell. 

The application is based on the results of phase 1 and phase 2 clinical trials that were presented at the ASH conference last December. Effectiveness was great -- 82% Overall Response Rate with a 75% Complete Response Rate.

However, as I noted in that link above, there were also some serious safety concerns with the treatment. Apparently, newer data, or something else in the application, has made the EMA feel better about those concerns (it's unlikely that the maker would make the application if there wasn't a good chance that it would be accepted. That Orphan Designation might have been a big help, given them some extra attention by the EMA during the application process). 

As far as I know, the maker hasn't applied to the FDA yet for approval in the USA. They may be waiting to see how things go with the EMA.

The EMA says it can take about 7 months for an application to be reviewed, so it might be a while before we hear more news about this one. In the meantime, I hope there is some updated information presented at ASH in December. If it is approved, it would be available in all European Union (EU) member states, Iceland, Norway and Liechtenstein. 

(I don't think I have any readers in Liechtenstein, which is a shame. I visited there once, years ago, and went to nice restaurant where I ate an ostrich steak. It was a memorable night. If there's anyone out there from Liechtenstein, please say hello in the comments.)

I'll keep you updated on all of this.

New Combinations for Follicular Lymphoma

Targeted Oncology ran a nice piece last week called "Exploring Novel Combinations in Indolent Lymphomas." It highlights a bunch of studies that are being conducted that involve trying different combinations of treatments to find something that improves outcomes without increasing side effects too much.

A lot of the research being done centers around R-Squared, the combination of Rituxan and Revlimid (also known as Lenalidomide). As you may know, R-Squared was approved with much celebration. It was the first treatment that was shown to be as effective as traditional chemotherapy. As such, it showed that it was possible for treatments that are more targeted to be a viable alternative to chemo. (Traditional chemotherapy likeR-CHOP and Bendamustine is often very effective for Follicular Lymphoma. The problem is, while chemo kills cancer cells, it often kills healthy cells as well.)

So while R-Squared is effective, it's not better. And that's an important distinction. It doesn't have the same side effects as chemo, but it also doesn't have fewer side effects. Just different ones. The official term for this is "non-inferior." That was the outcome of the large clinical trial that led to R-Squared being approved by the FDA -- it's not better than chemo, but it's not worse, either. But if it isn't better (that is, either more effective or safer), then it can't really replace chemo.

That's kind of where this article begins -- R-Squared came close to knocking chemo off the throne, but it didn't quite do it. So the next step is to find some way to make R-Squared more effective. That's what will make it superior to chemo, not just not inferior.

An example of this is the combination Tazemetostat + R-Squared, as I wrote about last month. R-Square is great, but adding a third treatment that goes after cancer cells in a different way just might make it better. Again, the problem is that it can also introduce a third set of side effects that can make things worse (though that doesn't seem to be the issue with Tazemetostat + R-Squared).

The article looks at a few others, though they aren't all being tested for Follicular Lymphoma. (The article is about indolent, slow-growing lymphomas, not just FL). This article is a summary of a presentation from the annual meeting of the Society of Hematologic Oncology (SOHO).

Some of the highlights:

• R-Squared is being combined with Epcoritamab, a bispecific antibody. The research is very early, in stage 1 and 2 trials, involving 66 previously untreated FL patients, but the results are good, with about 80% of patients in the trial getting a response.
• Another bispecific, mosunetuzumab, is also being combined with Lenalidomide (but not Rituxan) in a phase 3 trial with similar results. 
• Some other combinations focus on what are known as protumoral macrophages. Macrophages are another type of immune system cell, like the B cells that turn cancerous in FL. When macrophages become pro-tumorous, they allow cancer cells to grow. Some treatments target this process, including the BTK inhibitor Acalabrutinib. It is being combined with R-Squared in an early trial with 29 patients. It's doing well in the trial, with no new side effects when compared with R-squared, but it's also not much more effective. 
• Another BTK inhibitor called Zanubrutinib is being combined with Obinutuzumab (a monoclonal antibody like Rituxan). In a phase 2 trial, the combination is more effective than just Obinutuzumab.
  

A lot of these combinations are in early trials, as the article points out. But it does show that the approach is still very much on the minds of researchers. As exciting as CAR-T and bispecifics are on their own, there might be even more reasons for excitement if they are combined with other treatments. As long as the side effects remain manageable -- not worse than the side effects of the individual parts of the combination -- then there's some promise. 

All some fun things to keep an eye on.

How Smart is Cancer? Some Thoughts

I got a Google alert yesterday for a news release from The University of Miami's Miller School of Medicine. The title of the release is "Blood Cancer is Smart. Research is Smarter."

I was very curious about where this was going. It turned out to be a fairly standard news release from a university, discussing the research that some of its professors are doing (in this case, some of its blood cancer specialists). It's good stuff that they're doing there.

What really caught my eye, though, was the idea that cancer is "smart." I have some mixed feelings about that.

I'm certainly guilty of anthropomorphizing cancer -- talking about it like it's a person instead of a general name for a whole bunch of diseases. Sometimes it's easier to explain things to people if we treat cancer as a thing with a brain that can make its own decisions and take action to grow on its own and do things to evade treatment. I use a whole lot of comparisons when I write the blog. I think they're helpful (I certainly hope so). But I also know that comparisons have their own set of implications.

And it's not just me who does it. Sometimes we explain things to ourselves in ways that make it easier (or harder) to deal with being a patient. I wrote a piece a while ago where I talk about how it feels to have a slow-growing blood cancer. I compared it to being in a bar, seeing someone else who is staring at you, knowing that the other person is looking for a fight.

Making cancer into something recognizable can make it easier to deal with. Calling ourselves "warriors" makes it easier to feel like we're doing something other than watching and waiting. Thinking of cancer as something "smart" makes us feel like doctors might be smarter and can get us out of this mess.

I remember, many years ago when I was first diagnosed, writing in the blog about cancer humor. I still find jokes about cancer very funny (if they're good jokes, of course). You can probably find the blog post easily enough if you search. But I remember saying something along the lines of, I'll never stop laughing, because I  don't want to give cancer the satisfaction of making me sad.

At the same time, reading that title, it felt to me like it was giving cancer too much power. Is cancer "smart"? No. Because it can't make decisions. It can't target us. It can't problem-solve when it is confronted with a new treatment.

And I'm not sure treatments are "smart" in that way, either. I understand why they're called that. Compared to the very "stupid" chemotherapy, which kills whatever it comes across, newer treatments are "smart" in that they do a much, much better job of finding and killing cancer cells, rather than healthy cells. (Though they don't spare all healthy cells.)

And looking at the article, the doctors who are interviewed never call cancer or cancer research "smart." It's a clever headline.It certainly caught my attention.

But for me, it was a good opportunity to think some more about the language we use to talk about cancer, and the ways that our words shape our attitudes, and maybe our actions.That's always worth a little bit of reflection.