Venetoclax Phase 1

The Journal of Clinical Oncology has published the results of a phase 1 study of Venetoclax, in an article called "Phase I First-in-Human Study of Venetoclax in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma." The article reports on a phase 1 study, which means it is very early on in the process, but it is promising.

The treatment being studied in Venetoclax (also known as Venclexta and Venclyxto and ABT-199). Venetoclax is a Bcl-2 inhibitor. That probably requires some explanation.

Bcl-2 stands for "B-Cell Lymphoma 2," and describes a particular gene that controls a particular protein. These proteins are important because they help tell a cell when to die. Too much Bcl-2 means the cells don't know they are supposed to die, which, of course, causes cancer.

(OK, it's slightly more complicated than that. Keep reading if you want the complicated version:
Bcl-2 becomes a problem when two chromosomes switch places -- number 14 and number 18. This switch is one of the genetic mutations that define Follicular Lymphoma. You might see it written as t(14;18) or translocation of chromosomes 14 and 18. That's a problem because when those chromosomes are switched, it puts the Bcl-2 from 18 next to something from 14, and when they combine, the Bcl-2 becomes a problem, and shuts off apoptosis -- the natural signal that tells a cell to die. No dying = cancer cell.)

The important thing is, too much Bcl-2 means the B cells don't die.

Venetoclax turns off the Bcl-2 gene, so the cells know that they are supposed to die.

Venetoclax  has been around for a little while. It's one of the treatments that the FDA approved as a Breakthrough Therapy in 2015, for relapsed and refractory Chronic Lymphocytic Lymphoma.

This phase 1study looked at a bunch of NHL types besides CLL, including Follicular Lymphoma. There were 106 patients in the whole study, and 29 of them had FL.

Of the 29 with FL, 11 had a response (4 Complete Response and 7 Partial Response) and another 17 had Stable Disease. Only 1 of the 29 got worse.

There are more details in the article about important parts of phase 1 trials: how much of a dose that certain patients were given (that was especially important for the Follicular Lymphoma patients), and what kind of side effects patients had (and there were a bunch, but they were seen as manageable).

The researchers think that while Venetoclax going to be effective on its own, it will probably be even more effective when it is combined with some other treatment.

But that's something for the future. For now, this seems promising. The results, once again, are very early, and there will need to be a lot of work until Venetoclax is ever approved. But it's something else to look forward to. We'll definitely keep an eye on this one.