Monday, November 7, 2016

ASH: CAR-T

ASH abstracts are here! Woo hoo!

Every year at the beginning of December, the American Society of Hematology holds its annual meeting, and some of the most interesting and exciting research in lymphoma is shared. It's an exciting time for a Cancer Nerd like me. This year, there are about 60 presentations that are related to Follicular Lymphoma, and as I've done in the past, I'll try to read and comment on the sessions that are most exciting and interesting to me.

An important thing to mention: there is lots of good stuff at ASH every year, but it's usually not peer-reviewed. That is, it hasn't been looked at and approved by other experts in the area. That doesn't mean it isn't valid -- it just means it might turn out to be not as exciting as it seems at first. Also, a lot of the research is very early, in phase I or maybe phase II trials, with small numbers of patients. Same warning there -- it might turn out later that the research wasn't as exciting as it had seemed.

But that doesn't mean we can't get excited about what might come in the future, right?

So let's start with this one: "T Cells Expressing a Novel Fully-Human Anti-CD19 Chimeric Antigen Receptor Induce Remissions of Advanced Lymphoma in a First-in-Humans Clinical Trial."

This one was on my list, and then I got an email from William, who comments here sometimes. The paper is reporting on a trial that William's wife is a patient in, so he has an interest in sharing the good results that are being presented.

The paper discusses one of the many variations on CAR-T therapies that are being tested these days. As the abstract explains, some CAR-T types are made with murine components (researchers are too polite to say "mice," so they say "murine"). Like Rituxan, which is also made with murine components, the body can have a reaction to those non-human parts of the treatment. So the researchers reporting here created a fully-humanized CAR-T treatment to get rid of that problem, one that seeks out the CD19 protein on lymphoma cells. The treatment is called HuCAR-19.

Patients were given low-dose chemotherapy (Cyclophosphamide, the "C" in CHOP, plus Fludarabine), and then the HuCAR-19. Some patients were given a second dose if things hadn't cleared up.

This was a very small study (11 patients), and researchers were interested in the safety of the treatment as much as the results. They got good news on both ends: there were some safety issues, but they were treatable. The safety issue they were most concerned about was
Cytokine-Release Syndrome. With CRS, so many cells are being killed at once that the body has an inflammatory response, and it can have very serious consequences, including death. The researchers were aware of this, and had treatment available. The other thing they were looking for, a Response to the treatment, was also very good -- an 86% Overall Response Rate. So HuCAR-19 has shown to be safe and effective in this small study, making it worth examining in a larger study.

The patients, by the way, had several different types of lymphoma. Two patients had Follicular Lymphoma, and both had Responses to the treatment. that's good news, and certainly something for us to all keep an eye on, should a larger study of just FL patients come about.

Back to William: his wife Gretchen was, as he said in his email, their "star performer." If you look at the link, she's Patient 2 in the chart at the end: a Complete Response and no CRS! Congratulations, William and Gretchen! I hope things continue to go smoothly.

(And if there's anything important that I left out, please let me know in the comments.)

And one more thing -- this is more great advertising for clinical trials. New treatments can't happen if people don't volunteer to test them out.

More on ASH in the days to come. Lots to be (cautiously) excited about.

4 comments:

William May said...

You have it right Bob - thank you. We are excited and blessed that Gretchen is participating in this CAR-T trial (NCT02659943).

Anonymous said...

Hi Bob,

I just wanted to mention that I too scanned the ASH 2016 abstracts this past weekend, looking specifically for CAR-T and Follicular Lymphoma news, and I posted some links on my blog at:

https://fnhlben.wordpress.com/2016/11/06/week-ending-1162016-car-t-abstracts-from-upcoming-ash-2016/

William (Bill) has been kind enough to read it and leave a comment there as well. Sorry I didn't spend more time actually adding my own commentary to the links as you have done, but I think there are a few items worth reading for anyone interested in the some of the latest clinical trial data re CAR-T and FL. For instance, FL patients achieving CR via CAR-T seem to be remaining in CR as these trials progress. Certainly good news for folks like Bill's wife and myself who have recently undergone it!

-- Ben

Lymphomaniac said...

Thanks, Ben. Keep up with that blog!

William May said...

Hello Bob

Here is some good news we learned from Dr. Steven Schuster (one of the gurus in CAR-T) during a Lymphoma Research Foundation "Advances in Immunotherapy in the Treatment of Lymphoma" teleconference Q&A on November 17. Results from his UPENN Abramson Comprehensive Cancer Center follicular lymphoma CAR-T clinical trial showed:

* Of his 14 follicular lymphoma patients 10 (72%) achieved a complete remission.
* No patient achieving a CAR-T complete remission has relapsed.
* The average time in complete remission today stands at about 2 years.
* If your complete remission is 2 years or greater you have the same survival odds as someone who never had follicular lymphoma.
* After 1 year about 50% of his follicular lymphoma CAR-T patients no longer need IVIG infusions.

William