ASH: ZUMA-5 and CAR-T and Follicular Lymphoma

The ASH Conference is over now, but the fun keeps coming.

As I said a few weeks ago, when I started looking at ASH, I said that there wasn't a lot of excitement about the Follicular Lymphoma research, at least in the days before it started. (Sometimes, if there's something really big and important that's going to be presented, the oncologists I follow on Twitter will start talking about it.)

As it turns out, there were a few (three, actually) presentations that got people excited. I'll share them over the next few days.

The first was the presentation on the updated results for the ZUMA-5 clinical trial. ZUMA-5 is one of the trials that is testing a particular CAR-T on different blood cancers. ZUMA-1 was the trial that got CAR-T approved for use with aggressive lymphomas, including transformed FL. ZUMA-5 is a phase 2 trial that is looking at CAR-T and indolent lymphomas, including the kind of slow-growing Follicular Lymphoma that most of us are dealing with.

The first results of the ZUMA-5 trial were presented at ASCO earlier in the year. The results were very good. Zuma-5 has 94 patients with relapsed or refractory indolent (slow-growing) lymphoma, 80 of them with Follicular Lymphoma. After about a year of follow-up, 94% of patients had a Response, with 73% having a Complete Response. Of the FL patients, the response was even better -- 95% Overall Response, with 80% getting a Complete Response. The results were good enough that the makers of this CAR-T version applied for FDA approval.

Now, about 6 months later, the question was, did those results hold up? Did the responses last even longer? That's an important issue with CAR-T. Early results from ZUMA-1 showed that about 1/3 of patients had a goof long remission, about 1/3 had a response that lasted a year, and about 1/3 did not have a response at all. Later trials show longer responses. 

The ASH presentation is called "Primary Analysis of Zuma-5: A Phase 2 Study of Axicabtagene Ciloleucel (Axi-Cel) in Patients with Relapsed/Refractory (R/R) Indolent Non-Hodgkin Lymphoma (iNHL)."

The trial has expanded, and these results look at 146 patients with indolent lymphomas, including 124 with Follicular Lymphoma. You can click on the link to find out more about the patients in the trial (like their age, gender, FLIPI scores, etc.). But this detail seems important --  55% of them were POD24, meaning their disease had gotten worse within 2 years of receiving immunochemotherpay, and 68% were refractory to their last treatment, meaning the cancer did not respond to the treatment.

The results were still great after 17.5 months. The Overall Response Rate for everyone in the trial was 92%, with a 76% Complete Response Rate. In patients with Follicular Lymphoma, the ORR was 94%, with an 80% CRR. The response rate was about the same for everyone, even those who were POD24 or refractory. And the response was durable -- at almost 18 months, about 62% of the patients who had a response still had that response.

Of course, the treatment came with side effects, as all treatments do. About 99% of patients had some kind of side effect, with grade 3 or greater (meaning more serious) in 86%. These included side effects that are common to blood cancer treatments these days, like nerve issues and blood count issues. About 7% has Cytokine Release Syndrome, which can be very serious. Most of the side effects were manageable enough to be taken care of by the time the results were reported, but a few serious ones remained for some patients. 

So, overall, this is great news for Follicular Lymphoma patients. This new data will obviously be considered by the FDA when they look into whether or not to approve this CAR-T for indolent R/R lymphoma patients. If results continue to hold up, we might see another option soon.

There are a couple of other interesting presentations to look at, too. Give me a few days to look into them a little more, then come back and read all about them.