Thursday, April 27, 2017

Fast Track for Tazemetostat

The FDA has given Fast Track designation to Tazemetostat for Relapsed and Refractory Follicular Lymphoma -- FL that has stopped responding to treatment.

A few things probably need explaining.

First, Tazemetostat is an EZH2 inhibitor. There are lots of inhibitors out there for Follicular Lymphoma, some of them already approved, and some still in the process. They all work by inhibiting, or stopping, cancer cells from doing something that they need to do to stay alive. Different inhibitors target different things.

EZH2 stands for "Enhancer of Zeste Homolog 2." It's an enzyme that gets controlled by a gene with the same name. EZH2 is needed for an important step in cell growth called "methylation." Without that step, cells can't make copies of themselves.

Of course, too much EZH2 means too much copying of cells, which is pretty much what cancer is -- cells making more copies of themselves than they should, until it all gets out of control. Too m uch EZH2 can lead to a bunch of different cancers, including prostate, breast, and of course, Follicular Lymphoma.

An EZH2 inhibitor stops the cancer cells from doing that necessary step, and so keeps the cancer in check. Tazemetostat seems like it's going to be able to do that.

The other thing that needs explaining is the FDA Fast Track process. It's one of a few different programs that the FDA has developed to make treatments available to patients sooner than the normal process. Normally, a treatment would have to go through all 3 stages of clinical trials, and then have all of the data submitted at the end of the process. That's when the FDA starts its review.

With Fast Track, the treatment begins its review during the process, rather than at the end. This allows the maker of the treatment to have more communication, earlier, with the FDA. So if any problems come up (like with the way a trial is designed), they get answered and fixed before they happen.

For Tazemetostat, it looks like the Fast Track designation is happening just as they are getting ready to announce results for their phase 2 clinical trial, which will happen in June at the International Conference on Malignant Lymphoma (ICML) in Switzerland. They are making a big deal out of this announcement, so I'm guessing we'll see some good results.

To be clear, this doesn't mean that Tazemetostat is going to be approved soon -- or ever. (It won't be reviewed based only on the phase 2 trial results -- that would come from FDA Accelerated Approval). It does mean that Tazemetostat might be approved sooner than it normally would have.

Worth keeping an eye on. Inhibitors of all kinds are certainly going to be a part of our future treatments.

Monday, April 24, 2017

HealtheVoices

I had a really wonderful weekend, and I'd like to tell you about it.

I spent the last few days in Chicago at a conference for online health advocates called HealtheVoices. (English speakers, did you catch that? Health e-voices, because we are online advocates, but also healthy voices, because we try to be voices that give good advice?)

I was invited to participate by the main sponsor of the conference, Janssen Global Services, a pharmaceutical company, who paid for me to get to and stay in Chicago for the weekend. I'll be honest, my first reaction was to wonder what they wanted from me in exchange for this, but they didn't want anything. In fact, they asked me to be sure to make this clear: Janssen Global Services paid for my travel expenses for the conference. All thoughts and opinions expressed here are my own.

So, first off, I have to thank them and say that the Janssen people I spoke with were all great, and I get the sense that they are truly interested in hearing from patients and using patient experiences and desires to help shape the products they offer, the way they conduct research, the way they design clinical trials, and the way patients are treated. I don't have any doubt that Janssen wants to make a profit, but the individuals who work for them, who I spoke to, have a truly personal investment in the conditions they focus on. It's easy to forget that, and it was really nice to see.

So what is HealtheVoices?

It's an annual conference where online health advocates can get together to share ideas, learn from experts, and get refreshed and inspired. There were about 70 of us, I think -- a few cancer advocates, including a few lymphoma advocates, but also people who work online to support patients with diabetes, Inflammatory Bowel Disorder, HIV, mental health issues, and other chronic conditions. As most of you know, when someone receives a diagnosis, often the first place they turn is the internet, hoping to find information and support. These are the people who provide it.

And they really are great people, as passionate and compassionate as you would expect from health advocates. We all had different health issues that we advocated for, but we shared some real similarities, as well. (You don't have to talk too long before you find ways to connect with one another.) Some of the great folks I met:

  • A young man who created a YouTube channel called Check 15, that asks you to do a cancer check on the 15th of every month. His videos are very funny, and are meant to remind you to get to know your body well enough to notice any changes. Regular monthly self-checks and screenings are ways to catch some cancers early on. (I especially enjoyed the Star Wars parody, but you all know what a big nerd I am.)
  • A delightful woman from Lymphoma Canada who shares many of my goals -- providing knowledge and support for patients as they live with Lymphoma. The Lymphoma Canada web site is in English and French, so those of you in France, Belgium, and other French-speaking countries should especially take a look if you're having trouble finding good information. 
  • A man who used his own experience to begin blogging about depression, and advocating for mental health awareness, especially for men. I've said it a bunch of times -- Follicular Lymphoma is an emotional disease as much as a physical one. Being aware of, and taking care of, our own mental health, especially when we are first diagnosed, is incredibly important. 
  • A woman who has survived breast cancer and uses her photography skills to inspire and support others. She has helped a loved one who is a Follicular Lymphoma patient (always fun to trade stories about bone marrow biopsies!) with genuine compassion.
There were many others, of course. These are the ones I'm thinking about this morning.

So what did I get out of this weekend?

Well, for one thing, it energized me. I'll be honest -- sometimes it's a struggle to write about cancer 2 or 3 times a week, especially when there are lots of other things going on with work and family and just life in general. I was definitely at a point where I needed some perspective and inspiration. I got it this weekend.

I learned a lot about different ways to be an advocate, both online and offline. And, again, I'll be honest, until I was invited to Healthevoices, I never really thought of myself as a "health advocate." I got into this by accident. But I'm embracing it now. I'm at a point in my life where I am willing and able to do more.

You probably won't notice any major changes to the Lympho Bob blog. I like it what I do with it, and I like being able to have the space to write about issues that need lots of space to explain them. I won't ever let anything else I do get in the way of the blog. It will always be my first priority.

But I am going to try some new things, too. I have had a Twitter account since 2009, but I have never used it. I am going to start to use it. I'm still thinking about how I'll use it, but if you are on Twitter, feel free to follow me at @Lymphomaniac. I'll start posting content there soon.

I am also intrigued by the idea of making videos. Still thinking through that one, too. I'm open to suggestions (assuming you really want to see my face and hear my voice).

And I learned about lots of ways that I can be an advocate offline, too -- ways that you would never notice, but that might allow me to represent Follicular Lymphoma patients' voices in important ways. I'll let you know about them at some point, too. I'll need to hear from FL patients to know what they want and need (and not just what I want and need).

Thank you all again for your support. If you have any suggestions at all for ways that I can help you, let me know. I always enjoy reading your comments and emails, which do help shape the blog. I'd love to know what else I can do to be an advocate on your behalf.

Wednesday, April 19, 2017

More CAR-T at AACR

I'm writing about CAR-T again because I find it so fascinating.

And once again, OncLive has an interesting piece on CAR-T.

There has been some great news ab out CAR-T lately about clinical trial results, but this OncLive piece reports on additional infomation that we are learning about how CAR-T works. Researchers found two biomarkers that could help predict whether or not CAR-T will work well for particular patients. In other words, if researchers examine the cells, and they find that they have certain properties, that may predict whether CAR-T will work.

Before we go on, a little background to remind us f what we are dealing with.

CAR-T is not a single treatment. It's more of a general term for a treatment approach that several research terms are taking. CAR-T stands for Chimeric Antigen Receptor T cells. T cells are immune cells that attack invaders in the body in different ways. CAR-T involves removing those cells from a patient and changing them so they recognize and attack cancer cells the way they would attack a virus or other invader.

One of the biomarkers that researchers discovered is called Polyfunctional Strength Index, or PSI. Let's step back again for this one. T Cells do a lot of different things, and there are a lot of different types, with each type playing a different role in the immune system's attack against an invader. So, for example, there are Effector T Cells, which respond to the invasion; Helper T Cells, whicn help out other white blood cells; Killer T Cells, which do the actual attacking; Memory T Cells, which remember an invader so a more efficient attack can be made next time. There are others, but you get the point -- different T Cells do different jobs.

Except some don't do just one job, but two or more jobs. These are called Polyfunctional T Cells -- they serve many functions, or do several jobs. According to the research, having more Polyfunctional T Cells meant a better chance at a Response.

The other biomarker was post-infusion T Cell proliferation, or how much the T Cells multiplied after they were put back into the patient. One of the really great things about CAR-T treatments is that they take advantage of T Cells being living things. Unlike chemo or other treatments, where the amount of treatment stays the same after it is put into you, T Cells naturally multiply -- if the invader is big and bad, the body produces more T Cells to attack it. According to this research, the ability to cteate more T Cells is another good sign of a response.

Put those two things together -- T Cells that do more than one job, and T Cells that multiply well -- and you have an even better predictor that the patient will have a response to the treatment.

As I said, T Cells are fascinating to me, even when they are working normally. They can learn to detect an invader, remember what it is, and beat it up in the future. B Cells are fascinating, too. And what's even more fascinating is that my own are turning against me. And now we have some very smart people figuring out how to reverse that and have them work to protect me.

We have pretty amazing bodies, don't we?

And amazing people who are figuring out how they work.


effector, stimulatory, attractor, regulatory, and inflammatory, - See more at: http://www.onclive.com/web-exclusives/car-t-cell-functionality-correlates-with-outcomes-offering-a-biomarker-for-response#sthash.ui4zrnEB.dpuf




http://www.onclive.com/web-exclusives/car-t-cell-functionality-correlates-with-outcomes-offering-a-biomarker-for-response

Saturday, April 15, 2017

ZUMA-1 CAR-T Trial

OncLive has been posting some really excellent stuff lately.

A couple of days ago, they posted a piece called "Lead ZUMA-1 Researcher Highlights CAR T CellFindings in NHL." The article is a short interview with Dr. Frederick Locke of the Moffitt Cancer center in Florida. He discusses the ZUMA-1 trial, which focused on using CAR-T against aggressive lymphomas, including DBLCL and transformed Follicular Lymphoma.

There has already been some stuff written about this trial (including the link above, which gets into the 6 month follow-up for the trial, and this on the 3 month follow-up). This interview with Dr. Locke gets into a little more detail about the study and its results. (I was hoping he would talk a little more of the transformed FL patients, specifically, but he doesn't.)

But he does highlight some great things: the very high manufacturing rate of 99% (in CAR-T treatments, a patient's T cells are removed and messed with so they learn to attack cancer cells, so almost every patient was successful in going through this process); the high Response rates (82% Overall Response, and 54% Complete Response); and the manageable, even reversible side effects (which included Cytokine Release Syndrome, where the body is overwhelmed by the sudden flood of immune cells responding to the problem) and some neurologic problems.

So while the ZUMA-1 trial isn't specifically about the FL that most of us have, it should give us hope about CAR-T in general.

Interesting interview. I recommend you read the whole thing.

Wednesday, April 12, 2017

Dr. Salles on Newer Treatments for FL

Hey, folks.

I've been really busy lately, and I've had a hard time finishing any blog posts. There is actually a bunch of interesting news on Follicular Lymphoma lately, and I've been trying to sort through it see what's worth writing about.

So for now, here's a link to another short video from OncLive called "Dr. Salles on New Agents Being Investigated in Follicualr Lymphoma."

It features Dr. Gilles Salles discussing briefly (it's only a 1 minute 19 second video) some of the more recent treatments being approved and tested: PI3 kinase inhibitors like Idelalisib and Duvelisib (which seem to help a particular group of patients with responses of a year or so), BTK inhibitors like Ibrutinib (again, a particular group seems to get help from this), and some immunotherapy treatments (which he thinks will be effective in combinations with other treatments).

That's all I have for now, but maybe it will satisfy whatever Follicular Lymphoma cravings you have for now.

More soon -- I promise.

Gilles Salles MD, PhD, Centre Hospitalier Lyon-Sud, discusses new agents being investigated for patients with follicular lymphoma.

PI3 kinase inhibitors are currently of interest in patients with follicular lymphoma who have failed prior therapy. A select group of patients will benefit from these drugs and the response generally lasts for 1 year.

A small portion of patients respond to BTK inhibitors, such as ibrutinib (Imbruvica), but only some of the responses are long lasting, explains Salles.

Additionally, immunotherapy has not had much activity as a single agent, but combinations are currently being investigated for patients with follicular lymphoma.
  - See more at: http://www.onclive.com/onclive-tv/dr-salles-on-new-agents-being-investigated-in-follicular-lymphoma#sthash.L9RaWgOH.dpuf
Dr. Salles on New Agents Being Investigated in Follicular Lymphoma - See more at: http://www.onclive.com/onclive-tv/dr-salles-on-new-agents-being-investigated-in-follicular-lymphoma#sthash.L9RaWgOH.dpufDr
Dr. Salles on New Agents Being Investigated in Follicular Lymphoma - See more at: http://www.onclive.com/onclive-tv/dr-salles-on-new-agents-being-investigated-in-follicular-lymphoma#sthash.L9RaWgOH.dpuf

Thursday, April 6, 2017

New RadioImmunoTherapy

My thanks to a reader named Anne from Norway who sent me some links to articles about Betalutin, a new RadioImmunoTherapy that is in trials in Europe.

Anne sent a link to an article in the Norwegian pubication Best Practices in Oncology/Hematology called "New Type of Radioimmunotherapy by Indolent Non-Hodgkin B-cell Lymphomas - Phase I / II Trial Showing Promising Results." 

The link will take you to the Norwegian site. Google Translate can help you from there if you don't read Norwegian (it helped me). 

The article is written by one of the researchers who has been working on Betalutin in Oslo University Hospital. It is different from other RadioImmunoTherapies Bexxar and Zevalin because they target CD20, the same protein on the surface of B cells that Rituxan targets. Betalutin goes after CD37. This is important -- when RIT attaches to CD20, it remains on the surface of the cell. But when it attaches to CD37, it actually goes inside the cell, where it can remain longer to do its job. The hope is that Betalutin will be even more effective than the other RITs.

First results of the study were actually presented at ASH a few months ago, but the article that Anne sent actually has updated results with a few more Follicular Lymphoma patients being discussed. It's still a small sample (38 patients, 27 with FL), and more hospitals in Europe are participating in the study now. Results are good so far -- 68% Overall Response Rate, with 38% getting a Complete Response.


A few things worth mentioning here:

  • RIT is a great thing. Betalutin might even be an improvement over other types. It would be great if we could make it more available in the U.S.
  • I really like when you all send me stuff that I missed. Feel free to keep doing that, either by email or in comments. There's so much out there on Follicular Lymphoma. I do miss some of it, and that's a good thing -- it just means there's more good news than I can keep up with. We should all be hopeful about that.
  • Finally, I love hearing from readers outside the U.S. I know I report a lot of stuff that's really specific to the United States, because that's what I hear about easiest. But it's great to get news like this from Anne. It's a great reminder that, even though we have some differences, we all have so much in common. We'd all be better off if we remembered that more often.
So thanks again, Anne. (I've been watching Lilyhammer lately, the Netflix show that was originally on NRK1 in Norway. You have a beautiful country. I'm putting it on my list of places to go when I finally get the kids out of the house.)