In layperson’s terms, what’s a P13K drug?

[DRM18]

Hi folks,

Apologies if this is old news, but I just read the attached interview, where the good doctor expresses excitement at P13Ks as alternatives to many current CLL drugs.

I think. I admit I read it rather quickly.

Here’s the link!

onclive.com/view/cll-paradi...

[cllady01 Former Volunteer]

The following link will tell you the answer to your question.

As you will note, there are 2 used in CLL.

drugs.com/drug-class/pi3k-i...

[sllincolorado]

I think I am on one for the Ultra V trial. Drug: Umbralisib

PI3K delta inhibitor. I take it daily as pills. Also take venetoclax. Trial also includes Ublituximab

recombinant chimeric anti-CD20 monoclonal antibody administered as an IV infusion.

I am about to start the 9th month of this trial. My counts look good but my nodes did not get back to normalish until I started the venetoclax. The idea with this trial is that combo might be better than monotherapy. My guess (this is really just a guess) is that for me this PI3K delta inhibitor would not have controlled my SLL presentation by itself. The nodes only went back to normalish after venetoclax was added.

[cllady01 Former Volunteer]

DRM18, sorry, it is may not fit "layman's terms"---the following paragraph says a bit better. Inhibitor of course is the main description.

pubmed.ncbi.nlm.nih.gov/256...

[cajunjeff]

Cells are complicated. They have proteins on their surfaces that regulate the cell and they have enzymes in the cell that react to help cells perform their function.

We have learned that cancer cells can have too many or too few of these surface and below surface molecules that keep cancer cells alive.

Inhibitor drugs target these enzymes inside the cells and “inhibit” them, allowing for the cell to die. Ibrutinib, venetoclax and duvelisib are all inhibitors that target different enzymes. Ibrutinib inhibits btk. Duvelisib inhibits the P13K enzyme that is thought to keep Cll cells alive. Idelalisib is another P13K inhibitor.

We don’t hear as much about P13K inhibitors in Cll because they can have bad side effects. But if we become resistant to other drugs, it’s nice to have options.

What about monoclonal antibodies? Are they inhibitors? Kind of, but they are not called that. Monoclonals target surface molecules of Cll like CD 20. Inhibitors usually target enzymes/kinases inside the cell.

[Loveroflife]

So I am on Venetoclax and Obinituzimab I feel like the article infers that these will not cure me. I was very hopeful for at least an 8-15 year remission. Now I feel like I missed an opportunity for a cure by not doing a triple therapy.

[cajunjeff in reply to Loveroflife]

Loveroflife, I would not second guess your choice. It could even be curative, they just do not know.

Every drug we add comes at a cost, not just an economic cost. The less drugs you take to do the job, the better.

Can I kill more Cll cells with triple drug strategies? Sure. But at what cost. If three drugs are better, why not 6? How about FCRIVO? The side effects and neutropenia and anemia risks can all go up with each drug you add.

It might be IVO gets more remissions than VO. It might be keeping ibrutinib in your back pocket gives you more survival.

I think VO is a great choice. Time will tell which combo works best. But even if IVO works best for most, maybe VO does for others.

[SofiaDeo]

Hear, hear, cajunjeff! We are all different, even if we happen to have the exact same gene mutations, mutation status, % of cells affected etc. we lead different lives, eat different foods, have different nationalities. As new technologies and drugs become available, things will change some more. No one can predict how long a remission holds, or if someone is cured. But statistically, things like morbidity and mortality are much improved compared to a decade ago. There's no reason to think progress won't continue, IMO. And second-guessing a treatment decision, well, I think we all wonder/worry a bit. But Loveroflife, you chose your treatment after weighing what your docs said, and it likely is the best decision for you at this point in time.