ASCO: CAR-T and R/R Follicular Lymphoma

I'm still working my way through the ASCO materials. I didn't get to see as many of the sessions live as I would have liked. (I had a visit from a vaccinated relative whom I hadn't seen in a while. That was worth the trade-off. I miss people.)

As I said before, I'm still not sure there was anything from ASCO that was a kind of game-changer for Follicular Lymphoma. But there were some definite trends, and one of those was the attention being paid to CAR-T for Follicular Lymphoma. In fact, there were 32 different sessions devoted to CAR-T and FL. Some of them looked at CAR-T types that have already been used on FL, and some were on new types of CAR-T.

(It's probably worth reminding you that CAR-T isn't one specific treatment, the way Rituxan is one specific treatment. Instead, it's a larger category of treatments, like chemotherapy or immunotherapy with several different specific types of CAR-T available. They all work the same basic way, but with some important differences that make each one special.)

If there was one session about CAR-T and FL that got people buzzing the most, it was probably "Efficacy and safety of tisagenlecleucel (Tisa-cel) in adult patients (Pts) with relapsed/refractory follicular lymphoma (r/r FL): Primary analysis of the phase 2 Elara trial."

So far, there have been two main CAR-T treatments that have been approved for Follicular Lymphoma. Both were approved for aggressive FL types, especially transformed FL. And both have been in trials to test how effective and safe they might be for other types of FL, like indolent refractory/relapsed FL (slow-growing, but stopped responding to treatment), or as front-line treatment (the very first treatment for a patient). 

One of the two, Yescarta, was approved in the U.S. a few months ago for use on R/R Follicular Lymphoma. The approval was based on the ZUMA-5 trial, and showed an Overall Response Rate of 91%. Very good stuff.

The paper linked above described results for a study of the other CAR-T that has been approved for some FL patients (those with aggressive FL) -- Kymriah (also known as tisagenlecleucel, or Tis-cel). Kymriah was the first CAR-T approved for anything in the U.S. (in 2017), beating out Yescarta. But Yescarta beat Kymriah is getting approved for R/R FL. A nice rivalry going there, if it means better treatment for all of us.     

In the phase 2 Elara trial, described at ASCO, Kymriah was administered to 98 FL patients. The patients had received between 2 and 13 treatments, and 60% had progressed within 2 years of receiving immunochemotherapy. In the end, 94 patients were able to be evaluated, and there was an 86% Overall Response (with a 66% Complete Response). That's slightly lower than Yescarta, but still an excellent rate.

But here's where things take a turn in Kymriah's favor -- safety. 65% of patients experience serious side effects, generally nerve-related and blood-count-related (as is typical in blood cancer treatments). But while 49% had some kind of Cytokine Release Syndrome, none had a serious CRS reaction.

Let's look at that again. Cytokine Release Syndrome (or a Cytokine Storm) has been the major problem with CAR-T. Essentially, when the immune system is being overloaded, the way it does with CAR-T, when T cells flood the body, an inflammatory response begins. The body releases cytokines, which signal other immune cells to be released, and the result is a very large immune system reaction which can lead to organ failure. Early CAR-T trials resulted in a few deaths from CRS, though researchers learned to recognize it quickly and deal with it before it became too serious.

About 8% of FL patients in the ZUMA-5 trial for Yescarta had serious CRS. But in the Kymriah trial described at ASCO, no patients had serious CRS reactions. That's a pretty major difference between the two.

The question is, will that carry over into a larger group? Fewer than 100 patients were in the trial -- normal for a phase 2 trial. But not a huge number. Word is that the maker of Kymriah will ask for FDA approval for R/R Follicular Lymphoma based on these numbers, and my guess is that the approval will come quickly. But I'd be very interested in a follow-up (maybe at ASH in December, or ASCO next year?), to see if it really is as safe as this trial suggests. Even if those numbers go up to the 8% that Yescarta has, it will still be pretty great. But if there has been some tweak in the last 4 years that has made it even safer, that would be pretty amazing.

I'm going to look through some of the other CAR-T abstracts from ASCO for more good stuff. CAR-T is going to be with us for good. It will be interesting to see if new versions are more effective/safer than the older ones, can be made more inexpensively, or have some other features that will make CAR-T the standard treatment for all of us, no matter where we are in our treatment time line.