Sunday, July 28, 2019

Approval for Rituxan Biosimilar

Last week, the FDA approved a second biosimilar for Rituxan. This one is called Ruxience (the first one, approved last November, is called Truxima).

A little bit of background and reminder:

A biosimilar is kind of like a generic drug. It follows the same formula (in a sense) as a treatment that has already been approved, and has probably been around for a long time. The difference is that a generic drug is chemical -- once you have the chemical formula for the drug, it should be pretty easy to recreate it. that's what a "generic" is. It's usually cheaper because the company making the generic didn't have to spend millions or billions of dollars developing  it.

A biosimilar works the same way -- someone else already developed it, and a new company is coming in and trying to make a copy. But a biosimilar is harder to make than a generic. A generic is made from a chemical formula. I biosimilar is made from something that is or has been alive. Rituxan is made from mouse cells. Re-creating it is trickier than it would be for a generic.

Because of this, biosimilars go through the same FDA trial process as any new treatment. The FDA wants to be sure the biosimilar is as effective as the treatment it is copying, and with the same level of side effects.

Ruxience passed the test. It has been approved as a replacement for Rituxan as a first treatment, as a combination treatment with chemo, as a maintenance treatment -- really anything that Rituxan would be used for for Follicular Lymphoma.

And because the makers of Ruxience didn't need to do all of the developmental work that the makers of Rituxan did, it should be cheaper. In theory, you now have three choices instead of one, in terms of using Rituxan.

But the reality is a little different. Old habits die hard, and some oncologists may want to keep using Rituxan instead of a biosimilar, because that's what they've been using since 1997, and they know it works, so why mess with it? It will be interesting to see how many oncologists are willing to change to one of the biosimilars.

But there's a second hurdle. The companies that made the original treatments have issued patent challenges on some biosimilars, making legal arguments that the biosimilars are too close to the originals. This has delayed some biosimilars from being available to patients. Truxima is one of them -- it was approved over 6 months ago but still hasn't been available. (The Biosimilars Council issued a report last month that said these legal challenges have cost patients over $1 Billion, since they could have been using the cheaper biosimilars.)

So this is great news -- to me, more choices is good for patients, especially when those choices have the potential to save us money on treatments. But there are some potential problems to overcome before that happens.

Wednesday, July 24, 2019

Reminder: Vote for My Blog


Just a reminder that the endorsement/voting period for the WEGO Health Awards is over in just a few days. I've been nominated for three awards: Best in Show: Blog, Patient Leader Hero, and Lifetime Achievement.

If you are so inclined, you can click on the badges below, and vote for me without having to go to the WEGO web site. If you'd like to see my profile, you can click here.

WEGO Health Awards are given each year to patient advocates. The "endorsement" phase goes until July 28. The top three vote-getters in each category go to the finals. A panel of judges will pick the other two finalists for each category. Then a different panel will choose the winners.

Thanks, as always, for your support.

Sunday, July 21, 2019

REGN1979: Bispecific for Follicular Lymphoma

Following up on a comment from William, who linked to an article about the Bispecific REGN1979. Lymphoma News Today reported on the results of a Phase I trial for REGN1979, with very positive outcomes for patients with Follicular Lymphoma.

(I'm going to be shameless for a second, and remind everyone that I write a monthly column for Lymphoma News Today called "Things That Give Me Hope." I might as well make my editors happy and see if I can't increase our readership a little bit.)

Anyway, REGN1979 is a Bispecific, a fairly new type of treatment. The "Bi" in "Bispecific" usually means "two." In this case, it means the Bispecific attracts and attaches to two different proteins. It's kind of like a double-sided Rituxan. As you probably know, Rituxan works by finding the CD20 protein on a B cell and attaching itself to it. REGN1979, as a Bispecific, does just that -- it finds the CD20 on a cancerous B cell. But then it also finds the CD3 protein on an immune cell -- the cells that kill invaders in the blood. By connecting a cancer cell to an immune cell, the Bispecific can bring them together and let the immune cell do its thing.

This study was actually presented at the ASH conference last December. The results then were excellent, with all 7 Follicular Lymphoma patients getting a response (5 Complete and 2 Partial). The Lymphoma News Today article reports on updated results that were presented at the European Hematology Association conference last month. Results are still excellent, though with a few more patients, they are not quite as high: 13 of 14 patients (91%) had a response, with 10 of 14 (71%) getting a Complete Response.

The side effects were "manageable," and included (83% of patients), cytokine release syndrome (57%), chills (54%), and infections (49%), as well as the blood count and nerve issues that are common in FL treatments. Four patients had to drop the trial because of the side effects they experienced, and more had their disease progress. Also, 27 patients dropped the trial due to disease progression and several patients enrolled in the trial died (though this seems to have come from issues unrelated to the treatment itself, but because they already had advanced disease or other health issues, which is not uncommon in phase 1 trials).

I'm interested in Bispecifics (there are a few of them out there in trials) because my oncologist thought I would be a good candidate for a trial for this treatment. I'm sure William was interested in REGN1979 because the article points out that two of the patients who had a response were also former CAR-T patients. As I have been writing about lately, CAR-T works very well for some patients, but not alll of them. So it's great to see that a Bispecific could work for them.

It will be interesting to see how REGN1979 and other Bispecifics work in the longer term, and if a phase 2 trial would show different results, especially in terms of side effects. A significant number of patients had to drop out of this phase 1 trial. But phase 1 trials often include patients who have disease that has progressed a lot, and are willing to try things. That can throw off the results (whoch is why they don't include the entire group, including the drop-outs).

As I said, I'm very interested in this type of treatment. I'm hoping I won't need any treatment for a while, but I'd like to see some updated results at some point in the future.

Tuesday, July 16, 2019

Increased Risk of Secondary Cancers in FL Patients

As cancer patients, we'll all need treatment at some point. As Follicular Lymphoma patients, we'll probably need more than one treatment. As an often slow-growing cancer, FL has a way of sticking around, or coming back, even after a successful first treatment. So second (and maybe third and fourth) treatments are common.

And, of course, all cancer treatments have side effects. Unfortunately, one of those long-term side effects might be that the treatment for cancer might actually cause a different blood cancer down the road. I remember discussing this with my oncologist years ago -- we talked about Fludarabine, a type of chemo, but rejected in because I was so young, and it carried a risk of the patient developing leukemia years later.

No one has done a large-scale study, though, that looked at the risks of secondary cancers (that is, developing a cancer other than Follicular Lymphoma) as a result of FL treatments.

Until now, of course. "Risk of Secondary Haematological Malignancies in Patients with Follicular Lymphoma: An Analysis of 1028 Patients Treated in the Rituximab Era" was published earlier this month in the British Journal of Haematology.


Researchers looked at 1028 patients from Finland and Spain who had been diagnosed with FL and treated between 1997 and 2016 (Rituxan was first approved in 1997, which changed everything for FL, and so that's why it's called the "Rituxan Era").

Patients were grouped on the type of treatment they received -- Anthraycline chemotherapy (probably CHOP), Bendamustine (also a chemo), other chemo (maybe CVP, which is CHOP without the anthracycline), radiation, surgery, or watch and wait.

They found that 14 out of the 1028 patients developed a second blood cancer -- about 1.1% after 5 years. They estimate that the number would be about 2.7% after 10 years.

For patients who had more than one treatment, the number was 0.5% after the first treatment, but rising to 1.6% after a second treatment.


Some of the risk factors associated with secondary cancers included having a high FLIPI score, having B symptoms at diagnosis, and having multiple treatments. Patients who had Anthracycline chemo (like CHOP) or "other chemo" had a higher risk for developing Myelodysplastic Syndromes and Acute Myeloid Leukemia (both blood cancers). There were no secondary blood cancers reported in patients who had Bendamustine as a first treatment.

The researchers conclusion is that, if more treatments increase the chance of secondary cancers, then FL patients should think about treatments that allow for long Progression-Free Survival -- longer times between treatments means fewer treatments. They also think there should be more emphasis on immunotherapy -- the newer treatments that are more focused on cancer cells, rather than traditional chemotherapy, which targets lots of healthy cells as well as cancer cells. Less chemo might mean fewer secondary blood cancers.

A few comments on this.

First, no cancer is a good cancer, and I wouldn't wish a second blood cancer on anyone. But I also think it's important to put the numbers in perspective. A 2.7% chance of a secondary blood cancer after 10 years means about 1 in 39 people will get one. That's a fairly small number, in my mind -- maybe worth the risk if a particular chemo (like CHOP) seemed to give me the best chance of survival. For most of us, there are probably lots of other choices for our situation, so maybe CHOP isn't the best choice. Like with anything, having an informed conversation with your doctor is so important. Be aware of your choices, and make sure you are satisfied with the choice.

Second, it would be really interesting to know more about the long-term effects of some of those immunotherapies they recommend. This study looks mostly at patients who were diagnosed before some of the more recent immunotherapies were approved, so we don't get any idea of the effects of treatments like CAR-T, or various inhibitors, or all of those newer monoclonal antibodies.

Finally, looking at both what kinds of treatments were studied, and what kinds weren't studied, I'm reminded of all of the options we have. There are lots of them, and lots more in trials, possibly being approved in the next few years. We're fortunate in that way. Choices can be overwhelming, but it also means there are probably more that fit our particular situation and our desires (for longer remissions, for greater Quality of Life, etc.). But that really does mean staying educated and having open conversations with a doctor who is willing to have them.

Saturday, July 13, 2019

More Cool CAR-T News

I'm going to assume you read the last post, and learned all about CAR-T treatments. If not, go do some reading and listening.

Now that you have the basics of CAR-T down, here are a couple of other cool new studies about it.

The first is called "The Tyrosine Kinase Inhibitor Dasatinib Acts as a Pharmacologic On/Off Switch for CAR T Cells," published in Science Translation Medicine. As you may know, one of the real dangers of CAR-T is Cytokine Release Syndrome, which happens when the body reacts to all of those T-Cells swimming around and killing things. It can be deadly. Doctors are better about identifying and treating CRS before it gets too dangerous.

But this study has found a way to deal with CRS by temporarily turning off the T-Cells. Dasatinib is an inhibitor that is used to treat some types of Leukemia. Like all inhibitors, it inhibits -- gets in the way of a process that cancer cells need to survive. The researchers found that giving Dasatinib to CAR-T patients can turn off the T-Cells. So if the T-cells are working too hard, and the body is reacting by releasing too many Cytokines, the Dasatinib will turn off the T-Cells for a few days and slow down any CRS possibilities. When the Dasatinib wears off, the T-Cells go back to doing their job of finding and killing off the cancer cells.

The other study is called "High Rate of Durable Complete Remission in Follicular Lymphoma after CD19 CAR-T cell Immunotherapy," published a couple of days ago in the journal Blood.

This article reports on a phase 1/phase 2 clinical trial that used CAR-T on patients with Tranformed Follicular Lymphoma (which are the patients that have FDA approval for CAR-T), but also some with Relapsed/Refractory Follicular Lymphoma (they have not transformed, but their last treatment stopped working, or didn't work at all).

In the small trial, 8 R/R patients and 13 Transformed patients were given a chemotherapy combination of Cyclophosphamide (that's the "C" in "CHOP") and Fludarabine. Then they were given the CAR-T. Results were good: 7 of the 8 R/R FL patients had a Complete Reaction, and 6 of the 13 Transformed patients had a Complete Reaction. (There were no Partial Reactions.) All R/R Follicular patients who had a CR were still in remission after a media follow-up of 24 months, and the Transformed patients had a median remission of 10.2 months. Side effects were manageable and in line with what we've already seen with CAR-T.

To me, it seems like the big news here is the Relapsed/Refractory Follicular Lymphoma patients. CAR-T is not yet approved by the FDA for these patients, and this shows that it could be effective for this group.

HOWEVER, this is a very small study, with only 8 patients. It shows that it's worth doing more research on this group (which is already happening anyway).

Another HOWEVER: there is a lot of excitement about CAR-T, and it's worth being excited about. But the news is mixed, in many ways. Not all of the patients had a Response. In fact, is was 13 out of 21 who had a Response, or about 62% -- pretty good, but not a miracle cure. Same with duration -- many had a 2 year response, but many had less than that. Still good, but again, not a cure.

My point is this -- there is lots of to be excited about with CAR-T, and lots of research going on that is helping doctors figure out how to make it better. As I've said before, my own oncologist thinks that, in 5 years, CAR-T is going to be a lot more effective.

In the meantime, we can still be excited about it, and we'll keep an eye on all of the good research that's being done. And, as always, if you want to know more, I recommend the blog CAR-T and Follicular Non-Hodgkin's Lymphoma.

Happy reading!

Tuesday, July 9, 2019

CAR-T Information

I've across two very recent sources of information  about CAR-T that I'd like to share with you.

As I'm sure you know, CAR-T is a blood cancer treatment, and it's one that is getting a lot of attention lately. CAR-T stands for Chimeric Antigen Receptor T-cell. A T-cell is a part of the immune system. T-cells track down and fight infections (like viruses or bacteria) in the body. But they don't fight cancer cells. So to create CAR-T, some of a patients T-cells are removed from her body, and then changed in a laboratory so they will recognize cancer cells the same way they would recognize other invaders like viruses and bacteria. then they are put back into the patient, and they do their work.

(Personally, I really like that it's called "chimeric," which comes from Greek mythology. A chimera is a monster with a lion's head, a goat's body, and snake for a tale. I always thought that was a cool monster. The Chimeric Antigen Receptor does the same thing, squishing a few different parts into one cell, so it can find and attach to cancer cells and then attract T cells to the cancer cell. But it's a good monster.)

CAR-T therapy is one of those treatments that get oncologists very excited. It works for a lot people (including a couple of readers of this blog), though not for everyone. I read recently that about one-third of patients will have a long-lasting remission with CAR-T (including those two readers), one-third will have a shorter remission (maybe a year), and one-third will not get any remission. My own oncologist is one of those experts who is excited about it, and thinks that in about 5 years, we'll see a much higher effectiveness rate.

Like all treatments, CAR-T has side effects, including Cytokine Release Syndrome, in which the body reacts to so many cells being killed off at once. It can be dangerous, even deadly, though doctors seem to be doing a much better job of expecting this side effect and dealing with it right away. CAR-T can also cause some long-term nerve problems.

And right now, it is only approved in the U.S. for patients with aggressive blood cancers, including Transformed Follicular Lymphoma.

That's a quick look at the basics. Now, those two sources.

The first is a British documentary called War in the Blood, which is running on the British TV station BBC2. I follow a lot of folks in that part of the world on Twitter, and they are all very excited about this documentary. It follows two blood cancer patients who receive CAR-T, and it sounds like an amazing and uplifting piece of work.

Unfortunately for me, the link above will only let people in the UK watch online (and on BBC2). So all of you residents of the UK, please let us know if you've watched the documentary, and what you thought of it. And if anyone outside the UK has found a way to watch it online, or knows of when it might be on TV elsewhere (maybe BBC America?), let us know that, too. (In the meantime, I'll just go to BBC America and happily watch whatever Idris Elba show happens to be on.)

The second source of information is much more accessible: The local radio show Yale Cancer Answers just did an episode on CAR-T, and it is available online. You can either listen to the hour-long show, or read (or translate) a pdf of the transcript.

This link will take you to all of the Yale Cancer Answers shows, listed by date. The CAR-T show is from July 7, 2019.

The show is sponsored by the Yale Cancer Center, which is where I see my oncologist. The expert who talks about CAR-T is Dr. Iris Isufi (she is not my doctor, though she oversees a lot of the clinical trials at the hospital, and so is probably the most up-to-date person on new treatments at Yale). The show is meant for a non-medical audience, so they explain things very simply. I think it's as good an introduction to CAR-T as you'll find anywhere.

Of course, if you're looking for ongoing information about CAR-T, I highly recommend the blog CAR-T and Follicular Non-Hodgkin's Lymphoma, written by those two readers I mentioned above, Ben (who received CAR-T himself), and William (who is actually a caregiver for his wife, a CAR-T recipient).

Good stuff.

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

UPDATE 7/16/19: "War in the Blood" is now available on YouTube:
https://www.youtube.com/watch?v=0Nu2qe-Gf_c
Thanks to William for the link.

Wednesday, July 3, 2019

Vote for My Blog!

I am pleased to announce that, once again this year, I have been nominated for three WEGO Health Awards.

Like last year, I have been nominated for "Best in Show: Blog" and "Patient Leader Hero."

(And this year, for the first time, I have been nominated for the "Lifetime Achievement Award" -- or so I've been told. It's not actually showing up as I write this.)

The awards are now in the "Endorsement" phase, and this is when you can vote for me. If you are interested in endorsing me (voting for me), please go to my profile page:

https://awards.wegohealth.com/nominees/13062

To vote/endorse, click on the orange box under my photo.

There should be a new box that opens up, that will give you a pull-down menu so you can choose which of the awards to endorse me for. (You should feel free to endorse me for all three awards, should you be so moved.)

Also, be aware that you may be asked for an email address. You can only endorse me once in each category, and the email address is their way of keeping track of that.


Endorsements close on July 28. Vote today!


If you'd like to know a little more about the WEGO Health Awards:
 
The awards are given in 15 categories, and are meant to recognize "exceptional patient advocates, influencers and experts who make a difference in the lives of patients and caregivers." (You can read descriptions of all the awards here.)

After the nominations are made, and endorsements are over, the top 3 vote-getters (those with the most endorsements) become finalists for that category. A panel of judges will look at the rest of the nominees and choose two more to go into the finals. A separate panel of judges will then pick a winner for each category from those 5 finalists.

Now, it's a big contest, so there are a couple of hundred people nominated in each category -- lots of competition. I wasn't a finalist last year, or the year before, and that was just fine. It really was very cool just to be nominated.

That said, as cool as it was to be nominated, it would be even cooler to be a finalist -- I'm not going to lie.

So consider given me an endorsement or three.

And thank you for being such great readers.