EHA 2019 | CAR T-cell therapy updates in CLL
Susan O’Brien, MD, of the University of California, Irvine, CA, tells about a Phase I/II trial which investigated the use of defined CD4 and CD8 CAR T-cell products in the treatment of chronic lymphocytic leukemia (CLL). This interview took place at the 24th Congress of the European Hematology Association (EHA) 2019, held in Amsterdam, Netherlands. Dr O’brien goes on to explain how response rates were very positive and toxicities were reduced.
Transcript (edited for clarity)
We heard a presentation on CAR-Ts, which is the liso-cel, the JCAR product and that was a phase I, II trial. Actually, we really heard about the Phase I component of the trial with two different doses in very refractory patients with CLL.
And the thing that makes this CAR-T a little bit different is that they use defined CD4 and CD8 products...
We heard a presentation on CAR-Ts, which is the liso-cel, the JCAR product and that was a phase I, II trial. Actually, we really heard about the Phase I component of the trial with two different doses in very refractory patients with CLL.
And the thing that makes this CAR-T a little bit different is that they use defined CD4 and CD8 products. So with most CAR-Ts you just expose all of the T cells and then you get whatever population you get in terms of a ratio of CD4 to CD8.
Here, they separate them out ahead of time and they put a defined ratio in. Does that make any difference? Well the thinking is that it may help with the efficacy, but also they feel that it allows for more controllable toxicity. And in fact the toxicity profile looked pretty good.
So what they showed was that there was the cytokine release was quite uncommon, really single digit percentages and neurotoxicity was… So I’m talking about grade three to four, was only about 22% or 20%.
So this does appear to be less than what seen in some of the other CAR-T trials in CLL in a very refractory population who had, in general, a fairly large tumor bulk and we know that there is some correlation between the toxicities and the amount of tumor that the patient has going into it.
They also had very good response rates and some very durable. The first dose level, where obviously there’s the longest follow-up, they had now three patients who are in complete remission out past a year, who are MRD negative. So that’s very exciting because if we extrapolate from other CAR data, most patients, it seems like, who’re going to relapse will relapse within the first one year, I would say.
It doesn’t mean that nobody can relapse after one year, but that gives you hope that the remissions are going to be really durable for who knows how long a period of time. So that product is a little bit different and providing very interesting data. Very early on. They now chose their dose level and they’re moving into Phase II.
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