ASCO: Bispecific + R-Squared

Before I get to more ASCO news, a quick announcement: I was nominated again this year for a WEGO Health Award.

Except there have been a lot of changes to the awards this year, starting with the name: It's now known as the Social Health Awards. Also, all of the categories have changed. So while there's no more "Best of Show: Blog" award, there is one called Revolutionary Researcher, which will be given to an advocate who "stays up-to-date on the latest research, treatments, and clinical trials. This patient leader has a knack for transforming complex information into layman terms for the greater community to act on." I'll be honest -- I'm kind of excited about this one. This kind of advocacy doesn't always get much recognition. 

The final big change this year is that the timing for the "endorsement" period (where people can vote for their favorites) is much shorter -- only a few days (June 27  to July 1). I'll put up a link when you're allowed to give endorsements next week, if you are interested in voting.

Now, on to more ASCO.

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The ASCO presentations I've been looking at so far have been a little bit broader, in a way, than I was expecting -- more about bigger lessons than about specific treatments (though there are always big lessons to learn from ASCO).

So here's one about straight up research: "Subcutaneous epcoritamab with rituximab + lenalidomide (R²) in patients (pts) with relapsed or refractory (R/R) follicular lymphoma (FL): Update from phase 1/2 trial."

The treatment discussed here is called a "triplet" -- three different treatments given together. In this case, the treatments are Epcoritamab, a bi-specific, and Rituxan + Revlimid (also known as R-squared).

On the surface, this is kind of a powerhouse combination. B-specifics are creating a lot of excitement in the lymphoma community, and are seen as a potentially less expensive option to CAR-T. And R-squared is being used as an alternative to traditional chemotherapy -- just as effective, with a different set of side effects. So putting them together seems like an excellent idea.

And the results discussed in this presentation back that idea up. It's an update to the phase 1 and phase 2 results of a clinical trial. Early results showed a 90% Response to the triplet, with 50% getting a Complete Response. In the update, which looked at 30 patients with relapsed or refractory Follicular Lymphoma, (a fairly small number, but typical for a phase 1/2 trial), 28 patients remained on the treatment after a median of 5 months (two left the trial because their disease progressed). And all 28 of those remaining continued to respond to the treatment. And 40% of the patients in the trial were POD24, a very high-risk group. But they also had lasting responses, which is great news.

5 months isn't a very long time (the longest in the trial was 12 months), so there will need to be more on long-term durability reported in the future. But the initial response is impressive.  That's the advantage of a well-constructed triplet --  you can come at the cancer cells from several different ways. 

Of course, the potential disadvantage of a triplet is that you have the possibility of 3 times the side effects. In this case, the bi-specific and the R-squared generally don't have overlapping side effects (according to the researchers). But that means potential for more side effects, just not as severe as they might be. These included infections (in 57% of the patients in the trial), injection-site reactions (50%), constipation (37%), fatigue (37%), and nerve issues (37%). Cytokine Release Syndrome was an issue for 50% (mostly grade 1 and 2), and all were taken care of within 4 days, except for one patient who had to discontinue the study.

So overall, this seems like an effective treatment combination with manageable side effects. 

It will be very interesting to see how well they do in future updates (maybe we'll see one at ASH in December?) and if the results justify a larger, stage 3 clinical trial. 

I've said before, it seems to me that combinations like this will likely be a part of our treatment futures. It's good to see that some treatments that do well on their own can work effectively together as well.

More ASCO soon.

The Biggest News at ASCO (It's Not About Lymphoma)

More from the ASCO conference:

Based on how many people outside the cancer community are talking about it, the biggest news at ASCO is this presentation with a not-very-exciting-title: "Single agent PD-1 blockade as curative-intent treatment in mismatch repair deficient locally advanced rectal cancer."

This is about a stage 2 clinical trial for a monoclonal antibody for rectal cancer, not Follicular Lymphoma (or any other blood cancer). But it has some lessons, big and small, for those of us with other cancers.

The treatment is called "Dostarlimab," and if you search for it online, you'll find all kinds of headlines in non-medical publications that do things like ask if this is a cure for cancer. The results of the trial are exciting -- 100% Complete Response in every patient in the trial, with no serious side effects. One of the few that keeps its excitement in check is from NPR, with the title "This experimental drug could change the field of cancer research." Still maybe a little too ahead of itself, but at least it says "could" and leaves some room for doubt.

Dostarlimab is a monochlonal antibody (like our old pal Rituxan). There are many, many monochlonal antibodies out there, and they do different things. Dostarlimab is an inhibitor, which means it doesn't attack cancer cells directly, like traditional chemotherapy. Instead, it inhibits, or stops, a process from happening, and when that process stops, the cancer cell has a hard time growing or staying alive. 

In the case of Dostarlimab, it is a PD-1 inhibitor. PD stands for "programmed death." Normal cells have a life span built in to them. Some cells last a long time (like nerve cells), which others die off quickly (like skin cells). It's kind of built in to the cell to have a "programmed death." The process that is supposed to make this happen gets messed up, and you get cancer (cells that won't die). A PD-1 inhibitor is designed to stop that messed up process and allow cells to die.  

The results presented at ASCO were pretty remarkable. The 14 patients in the trial had a 100% Complete Response -- the cancer disappeared for all of them -- and no severe (grade 3 or higher) side effects (usually, at least 10% of patients in a trial like this will have severe side effects).

The early results mean that standard treatment for rectal cancer, including surgery and radiation, followed by chemotherapy, could be a thing of the past. 

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So what are the lessons to be learned?

Well, first, as we all know, a 14 patient trial is tiny. The more patients in a trial, the more likelihood that those unheard-of results will even out. One of the things I like about the NPR reporting that I linked above is that it is mostly an interview with an oncologist who wasn't part of the study, who has an optimistic but realistic view of it. She expects that the 100% CR will go down in a phase 3 trial. There might still be excellent results, but probably not 100% (though it would be wonderful if there was that high a rate). Also, there is a 6 month follow up for the study, so it's possible that after some time, the treatment stops working. (Again, it would be wonderful if that wasn't the case.) It's also possible that, with a larger trial with more patients, some more severe side effects showed up. (Or maybe not.)

So the main lesson in all of this is, stay optimistic, but cautious. I think after 14 years, I've learned how to maintain that balance. I'm always hopeful, but I also know that things don't always work out when they are tested more.

But the other big lesson for us, as Follicular Lymphoma patients, is that Immunotherapy still holds lots of promise for us. There aren't a lot of new chemotherapies being developed (if any), because researchers are learning more and more about how genes affect cancer, and how the immune system can be manipulated in ways that make treatments effective. 

But all of that takes time. We've seen recently that another type of inhibitor can have issues for FL patients. Maybe a PD-1 Inhibitor will do the job, either by itself or in combination. (This article from about a year ago looks at all of the different Immunotherapies being researched for FL, including two well-known PD-1 inhibitors, Keytruda and Opdivo, that have been very successful in some other cancers.)

And that's probably the biggest lesson of all -- these things take time. The development of cancer treatments is a slow process, usually resulting in small steps forward. Maybe Dostarlimab will make a huge difference for the small group of rectal cancer patients that it helps. I hope so. And maybe then, FL researchers will find something in it that might lead to a new treatment for FL. But, again, that will take time. 

The best thing we can do (beyond hoping and praying)? Talk to your oncologist about clinical trials. The patients in the Dostarlimab trial decided to take a chance, not go through traditional treatments, and try something new. Talk to your oncologist about whether a trial might work well for you. It will help out all of us.

More ASCO news next time.

ASCO: Mosunetuzumab (EC Approval + ASCO)

 I still have a few ASCO abstracts that I want to write about, but I'm skipping ahead to this one: "CELESTIMO: A phase III trial evaluating the efficacy and safety of mosunetuzumab plus lenalidomide versus rituximab plus lenalidomide in patients with relapsed or refractory follicular lymphoma who have received ≥ 1 line of systemic therapy."

It's actually not a presentation that reports on results. Instead it's more of an announcement that a phase 3 clinical trial is coming. More on that in just a minute. 

The reason I was interested in this ASCO presentation/announcement is because this week, the European Commission approved Mosunetuzumab for Follicular Lymphoma patients who have already had two other treatments.

Mosunetuzumab is a bispecific. I've written about bispecifics before, but here's a brief reminder: I bispecific is kind of like monoclonal antibody like Rituxan. It looks for B cells that have a CD20 protein on the surface and grabs onto them -- the same thing that Rituxan does. However, the bispecific also looks for T cells that have a different protein (CD3) on their surface, and grabs onto that. This way, the bispecific brings the cancer cell close to the immune cell that can kill it off. 

It's a treatment that got my oncologist excited a couple of years ago when I asked him about what was new in Lymphoma treatments, and it's probably up there with CAR-T as the treatment that gets Lymphoma specialists most excited. 

Which is why lots of discussions about Mosunetuzumab compare it to CAR-T, like this one from Fierce Pharma, which points out that it is very effective, has tolerable side effects (like treatable Cytokine Release Syndrome), but can be given immediately, unlike CAR-T, which has to be manufactured specially for each patient. 

The EC approval is based on phase 1/2 trial results. In that trial, the Overall Response Rate was 80%, including a 60% Complete Response Rate. The median duration of response (how long it kept working) was almost 23 months. About 39% of patients had Cytokine Release Syndrome, all of which was resolved by the end of treatment. Other side effects included lower blood counts, fever,  and headache.

Getting back to the ASCO announcement: The phase 3 trial will look at Mosunetuzumab and Lanalidomide (also known as Revlimid). Half of the patients in the trial will receive that combination, and the other half will receive Lenalidomide + Rutuxan, also known as R-squared.

This should be a great trial. R-Squared, as you know if you've been paying attention to these things, is a big deal because it was the first FL treatment that was as effective as traditional chemotherapy for FL patients. It had a different set of side effects, but was as effective. It was seen as the start of a new era in FL treatment, one where we could move away from chemo.

In this phase 3 trial, the researchers will do a direct comparison between R-squared and a bispecific + Rituxan. That direct comparison is really important in a trial. It doesn't look back at an earlier study and compare. It makes sure everyone in the two parts of the trial are as similar as possible.

It will take a while to run the trial, analyze the results, see if the responses last, and then go through an approval process. So it will be a few years before any of outside of the trial can receive this combination -- and maybe we will never be able to, if the trial is unsuccessful.

But in the meantime, FL patients in Europe have a new arrow in their quiver, a new treatment option, if it seems right for them. I'm looking forward to seeing just how popular a choice it becomes.

(More ASCO commentary soon.)

ASCO: Unmet Information Needs

More comments on presentations at this year's ASCO meeting.

Yesterday (June 5) was National Cancer Survivors Day. A "survivor," according to the foundation that sponsors the day, is anyone who has been diagnosed with cancer and is still alive. So you're a survivor if you were diagnosed yesterday, or 14 years ago (like me). 

"Survivor" can be a problematic word -- lots of people don't like it, and for lots of reasons. Some people feel like it means their cancer is all gone, and it isn't -- even for people who don't have a disease that is incurable. 

I understand that. No word is going to describe everyone's experience. That is, what I like about that definition of "survivor" is that it also includes patients who are actively in treatment, or who haven't yet started treatment. It highlights how long the cancer experience goes on, from beginning to end.

So looking at ASCO abstracts yesterday, I paid special attention to the category called "Survivorship and Symptoms." These are presentations that focus less on the cancer cells and more on the experience. And here is where the idea of "survivor" is especially important. I've heard lots of cancer patients talk about how tough it is after treatment -- there just isn't a lot of support once cancer patients go into remission -- support for the long-term side effects, or for the emotional and mental issues that come from the experience. 

And it's why I like that "survivorship" can also include patients who have not gone into remission. Because there are a lot of unmet needs there, too. We can be so focused on the treatment that we forget about everything that surrounds it.

This is all a very long introduction to the presentation that I want to describe. It's called "A comparative study of unmet information needs of patients with lymphoma and CLL: North America and Europe." I'm linking the title, but I'm not sure it will take you to the poster right now. It might not be available for a few days.

The presentation describes a large survey conducted by the Lymphoma Coalition, an organization made up of a large number of smaller lymphoma-focused organizations from all around the world. In this study, they present some data from a huge survey of lymphoma patients and caregivers from around the world (almost 12,000 people), and compare some of the responses from Europe and North America. The questions are about Information Needs -- the places where lymphoma patients wish they had more information about their disease and the experience of living with it.

Honestly, it's not the comparison that I find interesting -- whether or not patients from North America or Europe have more questions about certain issues. It's more the total numbers -- there are many, many places where lymphoma patients feel like they need more information, no matter where they are from. 

I'm probably not supposed to do this, but I'm going to cope the chart that summarizes the results:

 

And in case the graphic makes it hard to translate, the categories are:

• Diagnosis and what it means
• Treatment options
• Support for self-care
• Psychological support/counseling
• Support for their family
• Side effects from their treatment
• Fertility
• Have not needed more information

I think what strikes me most is that the categories with the largest numbers are the ones that describe the most basic information: diagnosis, treatment, and side effects. That's a huge problem. My guess is that numbers that are really small (like "support for their family") aren't small because people know all that they need to know, but rather because they are so focused on getting information about the patient that they don't even have time to think about how it's all affecting their family.

I like to think that this blog maybe helps answer some of the questions that FL patients have about their diagnosis and especially about treatment. But I also know there are many, many people who don't read it, or who have tried and just didn't get anything out of it. 

And I hope that this study will find its way to oncologists and others who support lymphoma patients, and as a whole community, we find more ways to get vital (and basic) information to patients who need it.

It's a good time to remind people that I'm always available if you have questions or you are looking for resources or if you just need to vent to someone who is willing to listen. I'm happy to respond to emails. The important thing is that you get the information you need.

More on ASCO soon.