ASH Review: Epcoritamab

If there was a Big Winner for Follicular Lymphoma at ASH this year, it was without a doubt Epcoritamab.

Epcoritamab is a bispecific antibody, meaning it has two mechanisms working. On one side, it attaches to a protein on the surface of the cancerous B cell, and then also attaches to a protein on a T cell, an immune cell. In this way a bispecific uses the body's immune system to treat the cancer.

The research that has everyone so excited is the results of a phase 3 clinical trial, also published in the prestigious medical journal The Lancet, as "Epcoritamab, lenalidomide, and rituximab versus lenalidomide and rituximab for relapsed or refractory follicular lymphoma (EPCORE FL-1): a global, open-label, randomised, phase 3 trial."

The results really are pretty exciting. This is a phase 3 randomized trial, which means the researchers split a large group of patients into two, so they could directly compare the results of two different  treatments. This kind of trial is considered the most accurate (rather than comparing one group to the results of a trial that happened a few years ago). In this case, one group was given R-squared (Rituxan + Lenalidomide/Revlimid), while the other was given R-Squared plus Epcoritamab. There were 448 patients in the trial (a pretty large number), and all had relapsed or refractory disease (they had already had treatment, and it didn't work or no longer worked).

With a median follow-up of 14.8 months, the Overall Response rate for the Epcoritamab group was 95% (versus 79% for the R-squared group). The Complete Response Rate was 83% for Epcoritamab and 50% for R-squared. 

The Progression-Free Survival for the Epcoritamab group was higher, with estimated PFS of 16 months in 85.5% of that group versus 40.2% in the R-squared group. (They had to use an estimate because some patients hadn't reached the median time yet.)

With a "triplet" -- a combination of three different treatments -- like this one, safety is always an issue. Three treatments might mean three times the effectiveness, but can also mean three times the side effects or adverse events. Grade 3 (serious) adverse events were higher for the Epcoritamab group (219 of 243, or 90% of that group, versus 161 of 238, or 68% of the R-squared group), which was to be expected. Cytokine Release Syndrome, which can be very dangerous, was low grade for the Epcoritamab group, and was managed by the doctors.

I was going to link to a few videos of Lymphoma experts talking about the results, but they're kind of all the same thing, with the expert repeating the numbers and talking about how exciting this could be (like this one from OncLive). And I do think it's exciting, having finally seen all of the data.

Any skepticism I have comes from whether or not patients will have access to it. It does seem to me that bispecifics are probably more accessible than CAR-T (the two are often talked about together, including by me). CAR-T is great, but more expensive (as one recent bit of research pointed out), which is going to make bispecifics a more popular choice for those who make those decisions about cost. But there are going to be still less expensive options for R/R patients, probably. I hope FL patients can get the best treatment available, no matter the cost.

This isn't the last we're going to hear about Epcoritamab. There were many ASH presentations on this treatment, for many different types of Lymphoma. Two that I thought were interesting were the results of a phase 2 trial of Epcoritamab and Rituxan for untreated FL patients (97% Complete Response Rate in a small trial), and Epcoritamab and R-squared in untreated FL patients (95% Overall Response Rate). 

But it's that randomized, phase 3 trial that really makes me think that Epcoritamab will be around for a while. A large number of patients over a long period of time. It seems pretty likely that it will be a regular part of treatment programs. It might take a while to get to that point, but it probably will.

I'm still looking at ASH abstracts and watching and reading commentaries. I'll have more soon. 

EHA: Epcoritamab and R-Squared

A reader asked me a couple of weeks ago if I reviewed presentations from the EHA Congress, the annual meeting of the European Hematology Association. It's the European equivalent of the ASH meeting in the United States. It happens soon after the ASCO conference. I have written about some EHA presentations in the past, but as I told him, I sometimes have trouble accessing their abstracts. So it hasn't been something I have done on a consistent basis. EHA has some excellent research. But it's always been a matter of access.

This year, I figured out how to look at EHA abstracts. And I had some incentive -- I got many notices about a particular presentation, "CLINICALLY RELEVANT SUBGROUP ANALYSIS FROM THE RANDOMIZED PHASE 3 EPCORE FL-1 TRIAL: TREATMENT (TX) EFFECT OF EPCORITAMAB WITH LENALIDOMIDE AND RITUXIMAB (R²) IN R/R FOLLICULAR LYMPHOMA (FL)." 

The presentation is an update on the EPCORE FL -1 clinical trial. I wrote about this a few months ago. 

First, some background. Epcoritamab is a bispecific, meaning it has two mechanisms working. On one side, it attaches to a protein on the surface of the cancerous B cell, and then also attaches to a protein on a T cell, an immune cell. In this way a bispecific uses the body's immune system to treat the cancer.

The EPCORE FL-1 trial is a phase 3 trial involving 488 patients with relapsed or refractory Follicular Lymphoma. Half of the patients received R-Squared (Lenalidomide + Rituxan) and the other half received R-Squared + Epcoritamab. The earlier results from late last year, with a median follow-up of 14.8 months, showed an Overall Response rate for the Epcoritamab group of 95% (versus 79% for the R-squared group). The Complete Response Rate was 83% for Epcoritamab and 50% for R-squared. The Progression-Free Survival for the Epcoritamab group was higher, with estimated PFS of 16 months in 85.5% of that group versus 40.2% in the R-squared group. 

The updated results break down the comparison into some sub-groups to determine if the Epcoritamab combination holds up better for certain populations. What the researchers found was that Epcoritamab + R-Squared seems to work better than R-Squared alone no matter how they divided things up. 

The results were better for the Epcoritamab group regardless of the age of the patients. For patients under 70 years old, The ORR was 96% versus 78% for the R-Squared group, and the Complete Response was 84% versus 50%. In patients 70 or older, the ORR was 91% versus 81% and the CR was 79% versus 50%. 

When patients were divided into low versus intermediate/high comorbidity (with the NHL-5 scale, a measure of how other health issues like heart, lung, or kidney disease might affect survival), the Eporitamab group again did better. Those with low NHL-5 comorbidity in the Epcoritamab group had an ORR of 94% versus 76% for the R-Squared group, and a CRR of 81% versus 50%. In the NHL-5 High/intermediate group, the ORRs were 97% versus 84% and CRRs were 86% and 49%.

The same held up for patients who received one previous treatment (ORRs were 96% vs 80%, the CRRs were 87% vs 53%,) as well as two or more previous treatments (ORRs were 94% vs 78%, the CRRs were 77% vs 45%). 

All of that matters, of course, because it shows that the Epcoritamab combination will work no matter the population. One big concern for a "triplet" like this  -- a combination of three different treatments -- is that there is the potential for three times the side effects. Patients who are older, or who have other health problems, or have been weakened by multiple treatments may have more problems with a triplet. But that wasn't the case here.

One more breakdown of the data in this presentation had to do with Lenalidomide, which has the potential for dangerous side effects. As part of the study, the researchers tried different levels of Lenalidomide -- at full strength, at 70%, and at 50%. But even with less Lenalidomide, the Epcoritamab triplet did better than the R-Squared. 

So, to sum up, Epcoritamab on its own is very good. R-Squared is very good. Combined, they are all even better, without sacrificing safety. 

I still have a few more ASCO presentations that I'm sifting through. I'll try to do the same with EHA presentations as well. More to come soon.

 

Epcoritamab + B-R

The journal HemaSphere published new research last week on another Epcoritamab combo. It's an early trial, but it could be an effective treatment for some patients.

Epcoritamab has been getting a lot of attention lately. If you've been a regular reader, you know I've been saying for a few years that that the treatments that seem to get oncologists most excited these days are CAR-T and Bispecifics. And he bispecific that gets them most excited is Epcoritamab.

A quick reminder: a bispecific works by targeting two different proteins. One of them is on the surface of the cancer cell. So it works a lot like Rituximab, which also targets a protein on the cancer cell. But a bispecific also targets a different protein on a different cell -- a T cell, which is an immune cell. So bringing a cancer cell close to an immune cell, the bispecific helps the immune system work against the cancer. 

Epcoritamab works by targeting the CD20 protein on the cancer cell (just like Rituxan does) but also the CD3 protein on the T cell. It works very well, and there are more and more reports of it being used successfully in various combinations (like the recent presentation on Epcoritamab + R-Squared).   

In this research, the combination is Epcoritamab + Bendamustine + Rituxan. As many of you now, Bendamustine is a traditional chemotherapy. The article from HemaSphere is called "First-line treatment with epcoritamab in combination with bendamustine plus rituximab induces sustained remissions beyond 3 years in patients with follicular lymphoma." 

It's a pretty straightforward title. The article describes a phase 1b/2 clinical trial (meaning it looks at safety, like a phase 1 trial, but also effectiveness, like a phase 2 trial). The study involves 25 patients from the trial who have been diagnosed with Follicular Lymphoma but had not yet received any treatment. The patients received Epcoritamab + BR and thenwere given additional Epcoritamab for up to 2 years. 

At a median follow-up of 41.3 months, the Overall Response Rate and the Complete Response Rate were both 96%. In other words, 24 of 25 patients had a Complete Response. That's very high, and I can't remember any trial where the OR was the same as the CR. And at a median of 36 months, 87% of patients had kept that Complete Response. The 3 year Progression Free Survival was 83%, and the 3 year Overall Survival was 96%.

As for safety, the combination did not produce any new side effects, just the ones that were expected with either Epcoritamab or BR. However, those expected side effects were not minor. There was no high-grade Cytokine Release Syndrome (CRS) or ICANS (Immune Effector Cell Neurotoxicity Syndrome), which are perhaps the most serious possible side effects, though lower-grade CRS occurred in 68%. But there were other side effects. 92% of participants reported infections (a sign of a weakened immune system),   with COVID-19 being the most common (patients were enrolled in 2021). Injection site reactions in 56%. Fatigue in 52%. The most common grade 3side (more serious) side effects were infection (44%), and low white blood cell counts. In all, 72% of patients experienced a grade 3 or higher side effect of some kind.

The researchers point to the high CR rates and long duration as very positive things. But they also point out that a combination like this can potentially bring about serious side effects, and caution doctors to think very carefully about which patients would benefit from it instead of a different treatment with less serious side effects.

It's a small study, very early in the process, but probably justifies moving on to a larger study. It will be very interesting to see if the side effects become an issue. Epcoritamab is part of our future, no question. But how it ends up in our future -- as a single agent or in some combination -- will be worked out over the next few years.

 

ASCO: Epcoritamab and Safety

As I have said before, this year's ASCO meeting was short on Follicular Lymphoma presentations. One of the big focuses for FL was on bispecifics, and Epcoritamab made its presence known.

Epcoritamab is a bispecific, attaching to CD20 on the cancer cell and CD3 on the T cell. (You can read more about bispecifics in my last post.) It was approved for Diffuse Large B Cell Lymphoma (including DLBCL that arose from transformed Follicular Lymphoma. In February, it was granted accelerated review for Relapsed/Refractory Follicular Lymphoma. A decision is expected within a  few weeks.

So it's no surprise that it got lots of attention at ASCO this year. My guess is that it will be approved. I have absolutely no insider knowledge about this. Just in my observation, the makers of treatments tend to keep quiet if they are expecting bad news, and Epcoritamab isn't being quiet.

In one ASCO presentation, researchers focused on safety. Because Epcoritamab is already approved in the U.S. and Europe, there is a good deal of data on its side effects. Like other bispecifics (and like CAR-T), Cytokine Release Syndrome (CRS) is a concern. (As a reminder --  CRS happens when the body releases too many immune cells all at once. With treatments like bispecifics and CAR-T, the whole point is to get the immune system to go after the cancer cells. But when that happens, the immune cells doing their work will signal to other immune cells to come and help. Those signals are sent through cytokines, and a fast build up on cytokines results in fever, low pressure, breathing trouble, and other dangerous issues.) In the ASCO presentation "EPCORE NHL‑1 follicular lymphoma (FL) cycle (C) 1 optimization (OPT) cohort: Expanding the clinical utility of epcoritamab in relapsed or refractory (R/R) FL," researchers looked specifically at patients who at potential issues with CRS and tried to find ways to identify the problem early.  Patients were hydrated and given dexamethasone, and anti-inflammatory drug, and were able to avoid hospitalization. Similar studies seem common in CAR-T as well. There is an increased understanding of how common CRS is and how important it is to treat it as soon as possible.

In another presentation focused on safety, "Subcutaneous epcoritamab (SC epcor) administered outpatient (outpt) for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL): Results from phase 2 EPCORE NHL-6," patients were given subcutaneous Epcoritamab (by an injection rather than by an IV) and monitored for side effects. The results were similar to the other presentation, in that there was some CRS, but it was carefully monitored and treated, and there were no hospitalizations required. 

The two presentations are obviously related, but they are looking at different forms of the treatment. An IV has potentially different side effects than an injection (subcutaneous Rituxan had to go through a whole different process to be approved by the FDA, 20 years after Rituxan was first approved). An IV can be slowed down, as it often is with Rituxan, because of allergic reactions (that happened with me when I received it), whereas an injection gets all of it to you at once. But these two studies show that Epcoritamab can be administered safely no matter the form. Again, there just seems to be an increased awareness of the likely side effects that come with stimulating the immune system to intensely. 

And I'm sure the FDA has safety in mind as they finish reviewing the application for R/R Follicular Lymphoma. It's always a concern, of course, but even more so lately, it seems, as newer types of treatments are approved and new safety concerns arise. 

I'm guessing that I will have news about Epcoritamab's approval very soon. Stay tuned.

Epcoritamab + R-Squared (+ Pharmacists)

In my quest for some Follicular Lymphoma-related reading material during this slow news time, I found an article in Pharmacy Times called "Epcoritamab Plus Lenalidomide and Rituximab in Practice: A Focus on EPCORE FL-1." 

As you can guess, Pharmacy Times is aimed at pharmacists, the folks who manage and sometimes advise on medications. That's the angle that makes it kind of interesting.

It's mostly a summary of the EPCORE FL-1 clinical trial results. EPCORE is the general name for a series of studies that have looked at the bispecific Epcoritamab. The EPCORE NHL-1 study looked at patients with several types of Non-Hodgkin's Lymphoma who were treated with just Epcoritamab. The EPCORE  FL-1 study is the one described here, and is the one that got people very very excited at last year's ASH conference.  This trial involves only FL patients, and combines Epcoritamab with R-Squared (Rituxan + Revlimid, also known as Lenalidomide).

The article provides a good overview of all of the successful trials for Epcoritamab, and especially for EPCORE FL-1. This was a phase 3 global study, with 488 patients from 30 countries. Patients had refractory or relapsed disease and had previously received a monoclonal antibody + chemotherapy. Patients were divided into two groups: one received R-squared and the other received R-squared plus Epcoritamab. 

Results were very positive. After a median follow-up of 14.8 months, The Epcoritamab group had a 95% Overall Response Rate (versus 79% for the R-squared only group). Most other measures were better in the Epcoritamab group did better than the R-squared only group -- including Progression Free Survival, Duration of Response, and Time to Next Treatment. It's easy to see why people were so excited at ASH.

Safety was also good, with low white blood cells counts (neutropenia) and infections being the most common side effects. Cytokine Release Syndrome, a major concern, occurred in 26% of patients, but all cases were manageable. Other side effects are described in the article. This isn't really providing any new data, just a summary of what was already reported.

What I found so interesting, though, were the "pharmacy" aspects of the article.

For instance, the article goes into some detail about dose escalation, something that gets mentioned in most oncology articles, but not in much detail.

In the EPCORE FL-1 trial, the dosing was changed partway through. At first, patients received a smaller dose first, and then a larger second dose. But in later studies, it was divided into three steps instead of two, so patients received it more gradually. Researchers think this probably helped lessen the severity of some side effects, including CRS. 

It also goes into some detail about "premedications" -- intravenous hydration, an antihistamine, an antipyretic (like acetaminophen), and corticosteroids (preferable dexamethasone) -- as well as "postmedications," including two to three liters of oral fluids within 24 hours after receiving Ecoritamab, plus corticosteroids (dexamethasone again) for 3 days.

I can picture an oncology pharamacist reading the results of the EPCORE FL-1 in an abstract, and thinking "That's nice, but what were the premedications?!" 

And I say that with great admiration, from one amateur Cancer Nerd to a professional one.

I don't really think about the role that pharmacists play in our treatment. 

When I had my Rituxan infusions, I had a blood draw first. Then I met with the oncologist to make sure everything was OK and I was well enough for the day's dose. Then I went to the treatment room, where the excellent Nurse Sue took care of me for a few hours. But somebody had to prepare the Rituxan. Somebody had to worry about my premedication hydration and the antihistamine I needed when I had an allergic reaction. 

It's kind of cool to think that there's someone else behind the scenes, keeping an eye on things. The size of our care team is really large.

I don't ever remember talking to a pharmacist when I needed treatment, but education is certainly a job for pharmacists, and the article discusses the role that pharmacists can play when a patient needs education about any of the medications that are a part of this treatment process. 

It's just kind of nice to have a broader perspective on things. It's one more person who cares about us, and who is looking out for us. We're lucky to have these hidden angels.  

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: 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.

ASCO: Epcoritamab and R-Squared

Finally, I'm giving you some ASCO news. A little later than usual, but I'll try to review some abstracts over the next few weeks.

As I said in my last post, there are fewer Follicular Lymphoma presentations than in the past. Not sure why, since there's plenty of FL research going on. It could be that researchers are presenting results at other conferences instead of ASCO. Or maybe, with the FDA being a little more strict about the evidence they want before they approve a treatment, researchers are holding off presenting early results. Those are just guesses from me. 

Whatever the case, there are fewer FL presentations, but still some good stuff to share.

Over the last few years, there haven't really been any big "blockbuster" presentations on FL at ASCO. The last one was probably in 2018, when the results for R-Squared were presented. R-Squared (Revlimid + Rituxan) was a big deal because it showed that it there could be a non-chemotherapy option that was just as effective as chemo, even if its side effects were just as serious (though a little bit different). There was a lot of discussion about that presentation, and we're seeing how important R-squared has been 5 years later.

This year, I've only seen one presentation that has created a lot of excitement online, on Twitter and on oncology websites. It's #7506, "Epcoritamab + R² regimen and responses in high-risk follicular lymphoma, regardless of POD24 status." Yes, R-Squared is involved. 

The research reports on results of a phase 2 clinical trial, and it involves adding Epcoritamab to R-Squared for high risk FL patients. Let's look at all of those things.

Epcoritamab is a bi-specific, a newer type of treatment that gets a lot of Lymphoma experts excited these days. It operates sort of like Rituxan and other monoclonal antibodies, which attach themselves to lymphoma cells when they find a protein on the surface called CD20. A bi-specific is different because it seeks out a second protein (CD3) on the surface of a T cell, another kind of immune cell, and attaches itself to that as well. By bringing the cancer cell and the immune cell next to each other, the bi-specific helps the immune cell destroy the cancer cell. 

By adding Epcoritamab to R-Squared, we have three different mechanisms for finding and destroying cancer cells. Of course, that also has the potential for creating three times the side effects. A few weeks ago, the FDA gave accelerated approval to Epcoritamab for some Diffuse Large B Cell Lymphomas, so it has already been through some trials.

The twist in this ASCO presentation is that the research is focusing on POD24 patients. As you might remember, POD24 stands for "Progression of Disease within 24 months." FL patients who have received successful immuno-chemotherapy (like R-CHOP or B-R), and then have their disease come back within 24 months, have a lower Overall Survival than other FL patients. About 20% of FL patients are identified as POD24, and researchers have tried to make them a priority in the last few years.

A successful trial for this combination would be a big deal for a few reasons. It would help a group of FL patients that need the help, and it would do it without traditional chemo (which many of them have probably already had anyway).

So what are the results? Very promising.

With a median follow-up of just under 1 year, the 104 patients in the trial showed a 98% Overall Response Rate, with a Complete Metabolic Response Rate of 87%. (A metabolic response rate means the response was measured by PET scan.) That's excellent. The researchers look forward to reporting results again, after some time, to see if the results are durable, and last for longer than a year.

What about safety -- did the combo create lots of side effects? The researchers call them "manageable." About half of the patients had Cytokine Release Syndrome (all of which were treated successfully)  or nerve issues. Others included fatigue and injection site reactions (the Epcoritamab is an injection, not an IV).

At this point, it seems like the combination could be an excellent option for POD24 or other high-risk FL patients. It's a phase 2 trial, so it's a little on the small side. But there's certainly good reason to expand the trial and include more patients. 

As I said, this is probably the only FL presentation from ASCO that is getting a lot of wide discussion, and it seems like there is good reason for it. Definitely something to keep an eye on, and with the success of other bi-specifics, not really surprising. 

I'll have more ASCO news soon. No blockbusters, but some interesting research to share.

Epcoritamab Gets FDA Priority Review

A quick bit of news: The FDA granted Priority Review status to Epcoritamab for Relapsed/Refractory Follicular Lymphoma.

Epcoritamab is a bispecific antibody. As a bispecific, Epcoritamab acts like a monoclonal antibody like Rituxan, by seeking out and attaching to a protein on the cancer cell (in this case, it attaches to the CD20 protein, just as Rituxan does). But then it dos something else -- it attaches to a protein (CD3) on a T cell, a kind of immune cell. By bringing the T cell close to the cancer cell, it helps the immune system work on the cancer.

The Priority Review means that the FDA thinks Epcoritamab will offer significant improvements in either safety or effectiveness over what is now available for R/R FL patients. It will make a decision in 6 months, rather than the usual 10 months, so it is likely to decide whether or not approve by June 28. 

The Priority Review is based on the phase1/phase 2 EPCORE trial. These results were presented at the ASH convention a couple of months ago. The results of that trial were very good; the Overall Response Rate was 82%, with a Complete Response Rate of 63%, comparable to Mosunetuzumab, the bispecific that is currently approved for FL patients. 

One thing that I find especially interesting is that they are considering approval based on a phase1/2 trial. Though it's fairly large for an early trial (128 patients), the FDA has also been sending signals that they want to slow down on accelerated approvals. They'd rather see full, phase 3 randomized trials instead, which are more reliable and give more time for potential side effects to come to light. I've actually been working on a post on that very subject; I may have to speed it up and get it on the blog soon.

Regardless, this is good news, assuming that everything goes well with the review. As I have said several times before, bispecifics are one of the treatment types that seem to get Lymphoma specialists most excited (and I include my own oncologist in that group). So another bispecific option would be great for all of us. 

More to come, I'm sure -- I'll keep an eye out for news and commentary about Epcoritamab, and share any good stuff I see. 

Two Approvals and a Story

My email notifications have been very busy over the last few days, with news of treatment approvals in the US and in Europe. If I get that many notices, it must be a big deal. I'll tell you about them, but first, a story.

A couple of days ago, I went for my first CT scan in many years. It wasn't for cancer, but for a heart-related issue. (Everything is fine -- just needed to check on something to make sure it really is fine.)  I haven't had a cancer-related scan in a while because I haven't needed one, and my oncologist is pretty firm in his belief that if there isn't a reason to do a scan, we shouldn't do one. "Surveillance" scans, just looking to see if there are any problems, don't usually work that way. Something else happens that calls for a scan, and the scan confirms the problem. 

So that's what happened with my heart-related issue -- something else showed a problem that CT scan could confirm. It was different than any of my cancer-related scans. It was just a CT scan, not a PET scan, so there was no nasty liquid to drink, no IV with a contrast in my arm, no getting undressed. Just me on a table, gliding into a big donut. It took about 5 minutes. 

I've been so busy lately that I really hadn't had time to even think about getting this scan. So it wasn't until I was on the moving table that I even thought "Wow -- it's been a long time since I had a scan. I really don't like scans. There is way too big a chance that a scan is going to bring bad news." That little bit of scanxiety didn't kick in until I was in the middle of it.

And then the voice came on, the one that gives you instructions. So a male voice started speaking to me: "Take a deep breath....now let it all the way out.....take another breath.....now let it all the way out......Now breath in deeply and hold," but his voice went way up when he said "hold," like he was asking a question. Then he continued, "Now you may release your breath." This happened three times.

I almost messed up the scan because I started laughing a little.

The whole "hold" like it was a question was kind of funny. But then I started thinking about the last scan I had, several years ago, at my cancer center. The voice that spoke to me there had a British accent. So instead of saying "Now you may release your breath, " the British voice said "Carry on breathing."

"Carry on breathing" is not a phrase that we use in the US. I remember telling my kids about it, years ago, and them thinking it was very funny. 

So there I was in the CT machine, already smiling at the guy say "hold" like it was question, and now I'm also thinking about the British guy saying "Carry on breathing," and I know I'm about to laugh out loud and ruin this whole scan. 

Thankfully, I was able to hold in my laughter until I was done (thank goodness it was a short scan). But I did tell the technician about it, since she was looking at me funny when I was chuckling a little bit when she came back into the room. She thought it was amusing.

So it's nice to be in a place where I can laugh during a CT scan. I hope that's someplace we can all be someday, with no worries about anything. 

***************

Now, on to those approvals.

The first is from the US. The FDA approved Epcoritamab for two different situations involving Follicular Lymphoma.  

Epcoritamab is a bispecific, attaching itself to B cells with the CD20 protein, ans then to a T cell (an immune cell) with the CD3 protein. In this way, it brings the immune cell close to cancer cell, so the immune cell can take out the cancer cell. Epcoritamab was accelerated approved by the FDA for relapsed/refractory FL in 2024. Accelerated approval is kind of temporary, allowing the treatment to be used on patients while additional data is collected. So the first of the two new approvals is making the accelrated approval into a permanent approval. Epcoritamab can be given as a single agent for patients with Relapsed/Refractory FL who have had at least two treatments already.

The second approval is for Epcoritamab to be used with R-Squared -- Rituxan and Revlimid/Lenalidomode. R-Squared is being used more and more as a substitute for traditional chemotherapy, so just as there are combinations of chemo with new agents, there are also combinations with R-Squared. The potential problem with that kind of combination is that with three treatments, you have the potential for triple the side effects. In fact, safety was a concern when research on Epcoritamab was presented at the ASCO conference in 2024. But apparently there was enough data to lessen those concerns.

So we have a couple of more treatment possibilities in the US. (It has already been approved in Europe and Japan.)

The second approval is for Tafasitamab in Europe. This isn't a full approval just yet, but it's very close. This approval is the last step before it becomes official. It was recommended by the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP), which approved it for use with (again) R-Squared for Relapsed/Refractory FL who have had at least one other treatment. It needs to get its final approval from the European Commission.

Tafasitamab (also known as Monjuvi) is a monoclonal antibody, like Rituxan. But unlike Rituxan, which binds to the CD20 protein, Tafasitamab binds to the CD19 protein. So in theory, it should work well with R-Squared, since it works in a slightly different way. The same potential problems with safety can happen with this combination, but the clinical trial data seems to show that it was OK. Given how many notices I received about this, it seems like there won't be any major issues with it getting approval from the European Commission. 

I know that there is going to be some new data for Epcoritamab at ASH in a couple of weeks. I haven't looked to see if there will be anything new for Tafasitamab. I know I need to get moving on ASH previews. I hope to have some for you soon.

ASH Review: Epcoritimab + R-Squared

 OK, SH is over, and it's time to continue to look at some of the presentations that made some noise. We already looked at some of the FL presentations that got some attention (those presentations on diet and blood cancer had some people talking on Twitter/X). 

So now it's time to look at the presentations that are getting attention after the meeting is over. 

Let me first respond to a comment from a reader named Peter, who wrote about my post on the "triumph" of Tasafitamab. He wrote "I’m always a bit skeptical of headlines that use superlatives (like “triumph”), especially when they’re from less scientifically rigorous sources (like fiercepharma)....A good mantra I learned to repeat to myself, back when I was first getting diagnosed and learning about lymphoma, is “if something sounds too good to be true, it probably is”. I found it the best way to try to control my own confirmation bias."

Amen to that. And it is with Peter's words echoing that I present to you "342 Fixed-Duration Epcoritamab + R² Drives Deep and Durable Responses in Patients with Relapsed or Refractory Follicular Lymphoma: 2-Year Follow-up from Arm 2 of the Epcore NHL-2 Trial." 

This presentation looks at data from a phase 1b/2 clinical trial. (This means they have combined the phase 1 study, which focuses on safety, and the phase 2 study, which focuses on effectiveness -- they use many of the same patients rather than having to start a whole new trial). There were 111 patients in the trial, and they received the bispecific antibody Epcoritamab as well as the combination R-Squared (Rituxan + Revlimid, also known as Ledalidomide). The patients all had relapsed or refractory disease (their last treatment didn't work or had stopped working). 

The results were very good -- the patients had an Overall Response Rate of 96%, and a Complete Response Rate of 87%. That's pretty great. The treatment worked well no matter what the patients' treatment history was. Patients with POD24 had a CRR of 79%, for example. After a median follow up of 24 months, an estimated 69% of patients were still responding to the treatment, and 75% of those with a Complete Response had maintained their Complete Response.

The researchers note that the study took place during the Covid pandemic, and 57% of patients reported getting Covid at some point, resulting in a number of health problems, though there were no Covid-related decisions to stop Epcoritamab.  The most common side effects were were neutropenia (62%) and Cytokine Release Syndrome (51%). At a median of 25.3 months, 17 patients (15%) were still on the treatment; 41 patients (37%) had completed treatment as it was described in the study description; and 53 (48%) had stopped treatment for several reasons: 18 of them had their disease progress, 22 had severe side effects, 7 withdrew from the study on their own, 1 died, one left because of Covid, and 4 left becuase of a doctor's decision.

So why the "If it's too good to be true, it probably is" attitude? 

A lot of the post-meeting analysis will come in the next few weeks or months, at least from oncologists and oncology-focused web sites. The more immediate analysis come from other web sites, and that's where almost all of the news that I got about this presentation came from, namely, finance and investment web sites.

In other words, at least immediately after the ASH meeting, the folks who are most excited about this are the ones who will make some money off of it. 

I've struggled with this for years, and in the United States, we're in the middle of a very controversial situation that is related to it. I won't get into that, because I don't think I can describe my feelings about it very well. 

But I also have to have a little skepticism about the excitement that a new treatment regiment is generating based mostly on a press release from the company that has developed it. It might very well be one of the ASH presentations that oncologists are excited about, and that they'll discuss elsewhere. But I'm going to hold off on my excitement until then, especially given that almost half of the trial participants dropped out before they finished. In their abstract conclusion, the researchers point out that there are no new side effects, compared to the Epcoritamab trial that resulted in its being approved for FL by the FDA and the EU. (And despite there being some safety concerns about Epcoritamab, too.) A few people are talking about it online, but no one is really bursting with excitement.

The clinical trial had a few arms, so there were patients who received Epcoritamab and B-R, for example. It will be interesting to see what oncologists have to say about all of it in the next few weeks and months. I'll keep you posted.

In the meantime, be the good critical thinkers that you are. Stay hopeful, but realistic.

How Were My 2024 Predictions?

This will be my last post for 2025, so I want to revisit my last post from 2024, called "Year-End Predictions." Just for fun, I made three predictions about Follicular Lymphoma for 2025.

I'm guessing a lot of you saw the calendar turn to December a few weeks ago and thought, "I wonder how Lympho Bob's year-end predictions went? I've been dying to know if he was right, because he's always so right about everything!"  Well, here we go. Your wish is about to come true.

My first prediction was "Tafasitamab won't be the 'game-changer' that the headlines predict it will." I was right about this.

At last year's (2024) ASH conference, there was a lot of excitement about Tafasitamab (also known as Monjuvi). Tafasitamab is a monoconal antibody, and the results of a stage 3 clinical trial were presented at ASH, where Tafasitamab was combined with R-Squared (Rituxan and Lenalidomide).  I had written about it a few times after ASH. There were lots of commentaries that talked about how great the combination was, and how it would most likely mean Tafasitamab + R-Squared would become the default treatment for Relapsed/Refractory Follicular Lymphoma. That hasn't happened. As I wrote a year ago, it takes a lot to change an oncologist's habits, and unless there is a huge change in survival statistics, there will probably be some change, but not a lot of change. The "game-changer" headlines are often clickbait, getting people like me and the rest of you Cancer Nerds all excited and reading their articles. It seems like there is always some new great treatment that will change things for us. To be sure, treatments are getting better over time (the difference in the choices I had when I was diagnosed about 18 years ago, and those available now, is incredible.) But as I get older, I get more suspicious of news articles that are a little too excited about these things. Tafasitamab may end up being an important part of our treatment choices, but it isn't yet. It was approved by the EU a week ago, and by the Japanese health ministry about the same time.

My second prediction was "Epcoritamab will cause some concerns." Epcoritamab was another treatment that caused some excitement at the 2024 ASH conference. But it also caused some controversy. The effectiveness numbers were great, but the safety raised some questions. There were a few more deaths than were expected, but they were explained by the fact that the trial took place during the Covid pandemic, when some of the trial participants had lowered immunity. As I said in the post, "my gut tells me those concerns haven't been completely answered." Well, as you know if you've been reading lately, Epcoritamab was this year's darling at ASH, and the "game changer" language for Tafasitamab from last year was applied to Epcoritamab for this year. So I'm going to say I was wrong about this one. There were no new safety issues in the year that followed, and Epcoritamab might well be the great treatment that the headlines say it will be. I sure hope so -- the numbers are fantastic. But time will tell.

My third prediction was "There won't be any major changes to the FDA approval process." I'm thinking I'm right about this one, too. Last year, there was talk that the FDA might cut back on surrogate endpoints and focus more on Overall Survival. In other words, they would ask for more long-term data before making decisions, That didn't happen, but there was plenty of controversy at the FDA anyway. I won't get into it. If you live in the U.S. and you follow health news, then you know. There has been a change in leadership, some instability in key positions, and controversies in many areas of pubic health. I was hoping to find a link to an objective source that described the year that the FDA had, but I couldn't find one. I will say, despite the controversies, it doesn't seem to me that the oncology world was effected negatively by it. FL treatments were approved, and people remain excited. The approval process has been largely the same as it was before. We'll stay hopeful that it stays that way, and if it does change, it will be change for the good.

There are a couple of lessons here.

First, I'll say what I said last year when I made the predictions -- remember that I'm not an oncologist or a cancer biologist. When it comes to cancer advice, the best person to talk to is your own oncologist. It's fun to make predictions, but I'd never make a prediction that I thought would affect an individual's life. I wouldn't want that responsibility -- that's not fun. Sure, I got two right, but the one I got wrong, I got really wrong. If your oncologist is a Lymphoma specialist, ask them what gets them excited about Lymphoma research these days. Then watch their eyes get big and their voice get a little louder from excitement. That's the real fun.

The other lesson is a reminder that one year is not a lot of time when it comes to cancer research. We move forward, but in small steps -- rarely in giant leaps. And we don't know for a while just how big a leap it is. Best to enjoy the small victories when we get them, and hope they turn into something big.

I hope your 2025 finishes up wonderfully, and your 2026 brings you good health and happy times.

I'll be back next year. Still lots of small victories to write about.

Take care.

Epcoritamab + R-Squared: Interim Results

The makers of the bispecific Epcoritamab just issued a press releasewith some interim results from the phase 3 clinical trial for Epcoritamab and R-Squared (Revilid + Rituxan) for Relapsed/Refractory patients with Follicular Lymphoma. The press release points out some very good news. The combination has an Overall Respose Rate of 95.7%, an improvement over R-Squared alone (which has an ORR of 89%). It also had a higher Progression Free Survival; it "reduced the risk of disease progression or death by 79%."

The plan is to present the results at the ASH conference in December, where they will present all of the data. The FDA agreed to a priority review of the combination last month, meaning they should issue a ruling by November 30 (which would be before the ASH conference).

All of this sounds great, but I have some questions. And, to be clear, I'm not suggesting anybody is doing anything wrong.

Te press release gives very little detail. And there's a good reason for this -- they're holding off on releasing any details until the ASH conference, which makes sense. This is a "scheduled interim analysis," meaning they had planned to look at the results they had so far at this point in the trial. Because they haven't competed the trial, they don't want to give too much detail yet.

The other side to all of this is that they need to keep investors happy. A little good news will do that, and a fairly general statement with some plans for the future won't hurt either.

But for me, it all raises more questions than it provides answers. Last year, there were some safety concerns about Epcoritamab, though they were explained by the trial taking place during the Covid pandemic, when some trial participants had lower immunity which caused some side effects. The press release here says that there were no new safety issues with this combination -- only the side effects that were already known for the three different elements. But if there were already some concerns, saying this doesn't really answer the initial questions about safety.

Again, I'm not saying anybody is doing anything wrong. For me, this isn't really an issue with Epcoritamab or its makers. It's more about frustration with the larger system for approving treatments, and the place of the patient in it all.

I'm looking forward to the ASH conference, so we can see more of the data that this FDA application is based on. I have little doubt that the data presented will be positive and encouraging for patients. I hope my questions and concerns are answered. I just wish that I didn't have to have so many of them along the way.

Year-End Predictions

This is the last time I'll be posting in 2024. It's been an interesting year, for me personally and for the world of Follicular Lymphoma.

I had considered using this last post of the year to come up with a top 10 (or more likely a top 5) list of things that happened in 2024 related to FL. But honestly, I'm too busy and too tired, and even when I get a small break, something seems to fill my time. (Yesterday, it was our dog, who had to go to the hospital with an infection. She's doing fine. But my wife and I spent way more time than we wanted to trying to figure out how to get her to swallow her antibiotic pill. Our final solution involved American cheese, coconut milk-based yogurt, and cheese popcorn. But we got the job done.)

So instead of my going back and re-reading all of those posts and journal articles and figuring out how to rank them, I'm going to do something slightly different. I'm going to make three predictions about the long-term prospects of some of the FL-related things that happened this year. Maybe I'll remember to check in next year and see if I was right (though I think these might take more than a year to really work themselves out.

Prediction #1: Tafasitamab won't be the "game-changer" that the headlines predict it will. I've mentioned this a few times in the last month or so. The Big News fro the ASH meeting was the results of the stage 3 trial for Tafasitamab + Rituxan + Revlimd. Even before the ASH meeting, there were articles about how great the results were. And they were great. This is a non-chemo treatment with manageable side effects. It's been called a "game-changer." But to me, it's not going to change a lot of the ways that oncologists treat FL. As excited as many Lymphoma experts are about this, it matches the excitement that they had about R-Squared (Rituxan + Revlimid) a few years ago. But that doesn't mean that oncologists are recommending it. A survey by the Follicular Lymphoma Foundation found that only 6.2% of FL patients had received Revlimid (Lenalidomide), with or without Rituxan. I can't imagine that number is going to get bigger when a third agent is added to the mix. To be clear -- this combination is probably going to be approved by the end of 2025, and it's going to help a lot of people. But I predict that it won't be a game-changer. It won't become the default treatment for FL any time soon. Oncologists are creatures of habit. If you're seeing a generalist oncologist, get a second opinion from a Follicular Lymphoma expert if you can. See what other options are out there.

Prediction #2: Epcoritamab will have cause some concerns.  The ASH presentations for Epcoritamab, which was approved by the FDA this year, were very positive. It's the second bispecific approved by the FDA for FL. But the presentations also mentioned some safety issues. The same safety issues were voiced just after Epcoritamab data was presented at ASCO this year. The issues can be explained -- the clinical trial ran during the Covid pandemic, and like most FL treatments, Epcoritamab causes some immune system issues, which were especially important during Covid. Clearly, those issues were not enough to keep the FDA (or the EU) from approving it. But I have a feeling that there will be enough lingering concerns from oncologists that Epcoritamab won't be as widely used as it could be. I certainly hope that this isn't true, but my gut tells me those concerns haven't been completely answered. 

Prediction #3: There Won't Be Any Major Changes to the FDA Approval Process. This one is tricky. Back in March, I wrote about a movement to make the FDA cut back on surrogate endpoints and focus on Overall Survival. This would mean a longer, more rigorous approval process. However, in the second part of the year, political changes in the U.S. could potentially make it more likely that the FDA will loosen up regulations and be more friendly toward pharmaceutical companies, which  might make the process easier. Or maybe the opposite -- an FDA that does not have close relationships to people in the pharma industry. Honestly, I can't predict that, and we won't know what exactly will happen for another month at the earliest. But there is lots of speculation about potential good and bad changes at the agency and potential harm or help for cancer patients. My prediction? There will ultimately be little change. There might be a lot of big talk about change, but there will be very little actual change. Cancer treatments will remain safe and effective and will get approved only when they're ready. All of th talk won't match the reality.

So there you have it. My three FL predictions for 2025.

I want to remind you all that I am not an oncologist, or a cancer biologist, or a pharma insider, or anyone else that has any kind of information that would help with these predictions. Just a cancer patient who reads a lot. 

I hope you all have a Happy New Year. Eat your grapes, your black eyed peas, your soba noodles, your black bun, your crepes, and whatever else you eat to bring you good luck for the year. 

I'll be back soon with more. And you can all look forward to my diagnosiversary post in a coupe of weeks. I'll have some things to say.

 

FDA Application for Epcoritamab + R-Squared

A quick note about some treatment news: the makers of Epcoritamab are submitting an application for approval for Epcoritamab + R-Squared as a treatment for patients with Relapsed or Refractory Follicular Lymphoma.

Some reminders:

Epcoritamab is a bispecific antibody. Like other bispecifics, it works by bringing together a lymphoma cell and an immune cell (a T cell) by attaching itself to both. This allows the T cell to eliminate the cancer cell. Bispecifics are one of those treatment types that gets oncologists very excited.

Last December at the ASH conference, researchers presented data about Epcoritamab combined with R-Squared, from the phase 2 clinical trial called EPCORE-NHL-1. The data is being used for the application with the FDA comes from a phase 3 trial called EPCORE-FL-1. 

The ASH data was very strong, with an Overall Response Rate of 96%, and a Complete Response Rate of 87%. After a median follow up of 24 months, an estimated 69% of patients were still responding to the treatment, and 75% of those with a Complete Response had maintained their Complete Response. 

So what is the Overall Response Rate for EPCORE-FL-1?

I'm not sure.

The ORR is good enough that it's the reason for the application, but the press release says the researchers plan to present that data at a medical conference in 2025. Maybe that will be ASCO in a few weeks? Maybe the Lugano conference in Switzerland soon after that? Maybe another conference later in the year?

So for now, there's no data available for effectiveness or safety for the combination. That's not a reason for alarm or suspicion. The FDA application will need to be perfect, and checking and reaffirming the data is expected. So we'll have to wait and see what gets announced.

(Am I saying one of my end-of-year predictions might come true? Who knows. We'll see what the data shows and what the FDA says.)

But a potential new treatment is always cause for excitement. Here's hoping it all works out.

More to come soon: some ASCO previews, some thoughts about watching and waiting vs Rituxan, and other fun things.

ASCO Follow-Ups

Very quick post. I wanted to share a couple of follow-up or analysis pieces from ASCO.

About this time (maybe 3 weeks after ASCO is over), we start to see some commentaries and analysis from the conference. One of the many oncology websites will ask one or more cancer experts to comment on what they thought as most important or impactful from ASCO.

I have two to share with you. The first was sent to me by William, a long-time reader whose wife is a Follicular Lymphoma patient. It's from the website Healio, and features a very brief interview with Dr. Matthew Matasar from Rutgers Cancer Institute. In the video, he mentions several important presentations from ASCO, including the one that I mentioned before on Epcoritamab. He confirms that bi-specifics are getting a lot of Lymphoma experts excited.

The other link is for a podcast from ASCO that highlights developments in blood cancer research. The podcast features a conversation between Dr. John Sweetenham from UT Southwestern's Harold C. Simmons Comprehensive Cancer Center and Dr. Marc Braunstein from NYU's Perlmutter Cancer Center. 

Dr. Braunstein also mentions the Epcoritamab presentation as being particularly significant. He walks through the results of the study, pointing out the great numbers for effectiveness and mentioning the side effects. As he says, "I think the addition of epcoritamab certainly shows high overall response rates and we'll need randomized data to confirm the efficacy, but it's definitely encouraging in high-risk follicular lymphoma patients." In other words, a larger clinical trial will be necessary that provides a direct comparison to current treatments to really show how good it is. 

But, once again, both realize how important bi-specifics are becoming for Lymphoma.

I'm sure there will be more analysis of the ASCO conference to come, and my guess is that the Epcoritamab presentation will continue to be a part. I'm hoping that some others will get a mention as well, though as I've been saying, Follicular Lymphoma was not a prominent subject this year.

But there's still plenty to talk about. More to come soon.

ASH Preview: Travel Costs for Treatment

The Follicular Lymphoma Foundation has left their survey open for a few more days. Click here to fill it out, and be sure to ask your caregivers, spouses, and partners to fill it out as well. 

I bring this up for two reasons. First, because I want people to take the survey (especially caregivers, whose voices aren't usually heard). But second, because one of the features of the survey involves how long you'd be willing to travel to receive a treatment. It's a really interesting question that doesn't get asked much. For someone like me, with a medical school,and cancer center pretty close by, this isn't a big deal. But for lots of folks, travel to a cancer center can take a very long time, especially for a newer or more complicated treatment that can't be done in a doctor's office treatment room (something like CAR-T comes to mind).

So I'm highlighting an ASH presentation that looks at this problem: "782 Travel Burden and Travel Costs of Bispecific Antibodies in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma and Relapsed/Refractory Follicular Lymphoma."It's one of those Quality of Life research projects that needs more attention.

The research looks at patients with both DLBCL and Follicular Lymphoma, but I'm going to focus on the FL patients. (The difference between them is in how often they are given this particular treatment.)

Specifically, the research looks at Bispecifics -- Mosunetuzumab and Epcoritamab, which have been aproved for FL. These are among the "newer or more complicated" treatments that aren't available in every treatment room, so some patients with FL need to travel to get to them. Travel costs money, but it also costs time -- time in the car, in the treatment room, and away from a job. 

The researchers looked at 114 patients with FL and DLBCL over a year. They looked at the distance that the patients had to travel to get to their treatment, and how much time it took. Then they calculated the financial cost by applying U.S. government standard mileage rates (the amount per mile that people can be reimbursed for in some jobs) and how much money they lost from missing work (using average wages).

Because Mosunetuzumab and Epcoritamab require different schedules, they figured out how many doses each would require over a year, and calculated them separately.

So what did they find?

The overall average one-way distance traveled was 80.1 miles, and took 84.5 minutes. About 56% of the patients traveled less than 30 miles and 24% traveled more than 60 miles.  

When they added things up, the FL patients who had Epcoritamab traveled 4486 miles over 70 hours, costing the, $5758. The patients who had Mosunetuzumab traveled 3,044 miles for 54 hours, costing them $3907. That's significant.

I don't think the researchers are saying Mosunetuzumab is better than Epcoritamab because of the costs associated with travel. That's a very individual thing -- for someone like me, close to a cancer center, where I could receive either one, the costs probably don't matter all that much. The larger point is to make oncologists aware of these costs -- in money and time -- and to make sure they are a part of the conversation that they have with patients about treatment. It's easy to look at an article in a medical journal and say "My patients have a choice of treatment, and X looks like it is 5% more effective that Y, so that's what I will recommend." That 5% difference might not mean much if there's a 2 hour drive involved every week.

(And that, of course, is exactly what the FLF survey is getting at -- trying to get enough data to show oncologists that these things matter to patients, and that Quality of Life should be a part of any treatment decisions that they make.)

It complicates things for everyone when you start bringing in more factors to consider at treatment time. But it's so important to get that bigger picture. 

I'll keep looking for interesting Quality of Life research in the ASH abstracts, along with interesting research on treatments. Look for more soon. 

 

ASH Review from the Follicular Lymphoma Foundaton

The ASH meeting ended yesterday, so no more previews. Now we're into reviews. Over the next few weeks, there will be lots of Lymphoma experts writing articles and making videos that talk about what they found most exciting at ASH. They're helpful. They often provide more detail and analysis than I could get from the abstracts, and it's usually easy to see patterns when they all talk about the same thing.

For this first review, we'll look at a video sponsored by the Follicular Lymphoma Foundation. It features Dr. Jessica Okosun, a Lymphoma specialist and professor at Bart's Cancer Institute in London. (Prof. Okosun was one of the panelists for the FLF's webinar, "Charting Our Progress Toward a Cure" last summer.) 

You can watch Dr, Okosun's video here on YouTube, or go to the FLF's website and see it there with some additional commentary. 

The thing that excited Dr. Okosun the most was the research on Epcoritamab and R-Squared (Rituxan + Revlimid or Lenilidomide). If there was a standout for FL reseach at ASH this year, it was this one. Since it was presented a few days ago, I've seen about 20-30 articles about it, with phrases like "game changer" and "new standard." (I'm always a little skeptical about new treatments being talked about so excitedly. I'll get more into that at some point.) The results were also published in the prestigious medical journal The Lancet a couple of days ago, which is a bigger deal, since it means the data has been peer-reviewed by other experts. 

As Dr. Okosun says in the video, the research was a randomized trial with about 400 patients, half of them getting R-squared and the other half getting R-squared + Epcoritamab. The R-Squared group had a Progression Free Survival of about 11 months, with the Epcoritamab group had not reached its median after almost 15 months (meaning fewer than half of the patients had their Lymphoma return). 

She was excited about bispecifics in general -- there was additional research at ASH on Mosunetuzumab as well -- but she also pointed out some safety concerns. Bispecifics tend to increase the risk of infection in some patients, so as with any treatment, there needs to be some caution when giving it. 

Dr. Okosun was also excited about the research on the biology of FL that was presented at ASH. We still have some basic questions that we don't have answers to, like why FL comes back after it seems to have been treated successfully. She was excited especially about research by Dr. Karen Tarte, who presented data that looked at differences between FL cells at diagnosis and then at relapse. You can see that abstract here; I'll try to look at it and comment on it soon. 

As I said, there will be more commentary from Lymphoma experts in the next few weeks about what they found exciting at ASH. And I'm sure a lot of it will be about Epcoritamab. I have no doubt that it has the potential to make things better for Relapsed and Refractory FL patients. It will be a matter of getting it to them. 

More ASH reviews to come.  

 

Some Treatment Approvals outside the U.S.

I've said more than a few times that I know my perspective on Follicular Lymphoma is very much an American one. I tend to focus on treatment approvals by the FDA in the United States, and write about issues that affect Amercan patients. Which makes sense, of course, since I live in the U.S.

But I also try to keep up with things that are happening outside my country when I can. I have readers from about 80 different countries, according to my Google analytics. I want to provide relevant information to as many of you as I can.

So here's some news from the last couple of weeks that may excite some you.

EU approves Odronextamab

First, the European Commission has approved Odronextamab for patients with relapsed or refractory Follicualr Lymphoma who have had at least two prior treatments. 

If you've been reading the blog lately, you know that Odronextamab is a bispecific antibody, a type of treatment that many oncologists are excited about. You also know that there was some slightly revised data published recently from the clinical trial that was used to approve the treatment. And you also know that in the U.S., the FDA denied approval (delayed approval, really) for Odronextamab a few months ago because they wanted to see more data from a larger trial. So you folks in Europe have access to this sooner than those of us in the U.S.

EU Approves Epcoritamab

The EC also granted "granted conditional marketing authorization" for the expanded use Epcoritamab for patients with relapsed or refractory FL who have had two or more treatments. Epcoritamab is also a bispecific antibody. It was approved by the EC for Diffuse Large B Cell Lymphoma, so this approval makes it "expanded use." The "conditional" part of the approval seems to come from a planned study that the makers of the treatment will conduct to try to cut down on Cytokine Release Syndrome. But the treatment is now available. 

Epcoritamab was approved by the FDA about two months ago. So it looks like we have a draw, as far as whether Europe and the U.S. approved a bispecific before the other. We may need to go to a shootout.

(See? A Football comparison. I can write for non-U.S. audiences. I didn't even call it Soccer.)

EU Approves Liso-Cel

Finally, the European Medicines Agency approved a Type II variation application for Liso-Cel (also known as Breyanzi) for r/r FL patients with at least two prior treatments.Liso-Cel is a CAR-T treatment. Before I get into the FDA approval, it might be important to know what a Type II variation is. Then we can determine who won this football/soccer match....

But wait. What's this? Japan is on the pitch!

Japan's Ministry of Health, Labor, and Welfare has also approved Liso-Cel for r/r FL patients, but with only one prior treatment, not two. 

This changes everything! We have to sort this out before we can determine a winner of this match! I'll need to get back to you!

That was silly, I know. But truly, the winners are all of the thousands of r/r FL patients in many countries who now have access to the some of the treatments that are most exciting these days. Expanded options are good for all of us. 

And while many FL patients have relapsed or refractory disease after two treatments -- and those are probably the patients who need treatment options the most -- some of us have r/r disease and just one treatment, and others are still benefiting from their first, or have yet to receive treatment. So I hope there are more approvals coming soon that I can share with you. 

That would be some World Cup-level stuff.

 

Liso-cel

https://www.cancernetwork.com/view/ema-validates-type-ii-application-for-liso-cel-in-r-r-follicular-lymphoma

Epcoritamab Approval

The FDA granted accelerated approval to Epcoritamab for Relapsed/Refractory Follicualr Lymphoma yesterday. 

This was not a surprise.

The approval is for Relapsed/Refractory disease after two previous lines of treatment. 

Epcoritamab is a bispecific antibody. Like all bispecifics, it works in two parts. It attached itself to cancerous B cells (the way Rituxan works) but also attaches itself to a T cell, allowing that immune cell to work on the cancer cell. This will be the second bispecific available to at least some FL patients. 

The treatment got a lot of attention at ASCO a few weeks ago, and any concerns about safety were addressed in particular. That said, there will still be a warning on the box for "serious or fatal cytokine release syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity (ICANS)." This will be a standard warning, not a more serious "black box" warning.

The apprval is based on Epcoritamab's very good effectiveness. In the clinical trial that provided data for the approval, the Overall Response Rate was 82%, with a Complete Response of 60%. The median Duration of Response after 14.8 months was not yet reached, meaning more than half of the 127 patients in the study were still getting a response after that time.

This is, of course, good news for all of us. Another arrow in the quiver, as one of my oncologists used to say.

More to come.