SYMPHONY-1 Trial (Tazemetostat plus R Squared)

OncLive has a nice interview with Dr. Jennifer Effie Amengual of the Columbia University Irving Medical Center in New York. She discusses the SYMPHONY-1 trial, which is testing a promising treatment combination -- Tazemetostat plus R Squared.

Tazemetostat was approved by the FDA a few years ago for a subset of Follicular Lymphoma patients. Tazemetostat is an EZH2 inhibitor. EZH2 stands for "Enhancer of Zeste Homolog 2. EZH2 is an enzyme that is controlled by the EZH2 gene that controls tumor growth. Because Tazemetostat is an inhibitor, it stops EZH2 from allowing cancer cells to grow. 

As the interview with Dr. Amengual points out, one of the great things about Tazemetostat is its safety profile -- the side effects are comparatively mild (at least compared to traditional chemotherapy). To be clear -- there are side effects, and they can be serious. But they seems to be different from, say, CAR-T, especially cytopenias (that is, low blood cell counts, whether they are red or white blood cells or platelets). 

And that seems to be why the combination with R-Squared is appealing. R-Squared, as you may know, is the combination of Rituxan and Revlimid (also known as Lenalidomide). As I mentioned in my last post, R-Squared is a big deal because it was the first treatment that was shown to be as effective as traditional chemo, but with different side effects.

So you can see the pattern here -- effective treatments with different side effects that don't pile up on each other. 

One of the interesting things that Dr. Amengual discusses is a kind of comparison between this combination and CAR-T. The trial doesn't specifically compare the two, but she does bring up which patients she would recommend for each of them. She uses the phrase "younger, fit patients" to talk about who she might recommend CAR-T to. Particularly because CAR-T patients had likely been heavily pre-treated, already having received a few treatments already that would have potentially weakened their immune systems, a combination like Tazemetostat and R-Squared might be easier on older, less fit FL patients. 

The trial is now in phase 2, so they are testing how effective the combination is. Half of the patients in the trial will get Tazemetostat and R-Squared, and the other half will just get R-Squared. Definitely worth paying attention this one.

The interview on OncLive seemed pretty accessible to me, if you're interested in reading it. It's worth a look.