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!

3 comments:

Anonymous said...

Hi Bob,

This is actually the second published report on R/R Follicular Lymphoma patients with Car T. The first was done at U Penn where there were 14 patients with R/R FL and 11 responded with over 70% longer term remission. The evidence is adding up and hopefully larger trials like Zuma 5 (Yescarta) will release results soon so we can get approval for Car T for R/R FL. The link below is to the U Penn study.

https://www.nejm.org/doi/full/10.1056/NEJMoa1708566

icrazyhorse said...

Hello Bob

Someone in the UK finally posted "War in the Blood" so people in the US can see it.

War in the Blood

An intimate, feature-length documentary (1 hr 40 min) following two patients through groundbreaking ‘first in-human’ trials for CAR T-cell therapy, a treatment described as the beginning of the end of cancer.

https://www.youtube.com/watch?v=0Nu2qe-Gf_c

William

icrazyhorse said...

Hello Bob

REGN1979 Eliminated Cancer in Most Non-Hodgkin’s Lymphoma Patients in Phase 1 Trial

https://lymphomanewstoday.com/2019/07/09/regn1979-non-hodgkins-lymphoma-phase-1-trial/?utm_source=LYM+E-mail+List&utm_campaign=b4addf4899-RSS_THURSDAY_EMAIL_CAMPAIGN_US&utm_medium=email&utm_term=0_4783db36f7-b4addf4899-71463317

Regeneron‘s bispecific antibody REGN1979 is showing outstanding clinical effectiveness in B-cell non-Hodgkin’s lymphoma patients who received prior treatments, including those who progressed after CAR T-cell therapies.

The treatment completely eliminated the cancer in 71% of follicular lymphoma and 57% of diffuse large B-cell lymphoma patients participated in a Phase 1 clinical trial, the company announced.

Bill May