Unmutated patients on venetoclax?

[HikerBiker]

I just watched the video "Evolving Front-Line Therapy in Chronic Lymphocytic Leukemia" posted by EugeneL2. In it, she refers to the trial where patients on venetoclax + obinutuzumab had much better results than those on chlorambucil + obinutuzumab. However, she also noted that mutated patients on both treatments fared better than unmutated patients.

As an unmutated patient who decided to go with venetoclax over acalabrutinib I wonder about the unmutated factor. Don't unmutated patients do equally well on the BTK inhibitors?

[cajunjeff]

According to the article below, the answer to your question is yes. I remember reading somewhere, however, that while ibrutinib works well with 17p Cll too, 17p still carries some additional risk even with ibrutinib.

oncotherapynetwork.com/leuk...

[MaxSmart]

Hi Hiker Biker, I just watch the video myself because I am unmutated. I didn’t really get a clear answer watching the video but then I watch a second video where Dr. Lamanna clearly states that unmutated don’t do as well long term as mutated. But looking at it more closely she’s using a slide dated 1999. It’s around 18 minutes into the video. Around 24 minute mark she says mutated and unmutated do equally well on Venetoclax.

youtu.be/wODcksQ5SoE(Not working as expected?)

[HikerBiker in reply to MaxSmart]

Interesting that Dr. Lamanna came to that conclusion from the same study as Dr. Woyach was referring to in her presentation. Here is the slide from Dr. Woyach's presentation, and you can see there is a clear difference between mutated and unmutated patients in the Murano study: drive.google.com/file/d/1Uu...

[Canuck901]

Yeah unmutated 17p and TP53 are the unfavourable high risk markers and usually have shorter remissions compared to others without the markers. Also everyone’s CLL is different and some people have had good remissions from I plus V and A plus V I believe

Seems to be good synergies between both together

Newer combos seem to be much better for all favourable and unfavourable markers

targetedonc.com/view/acalab...

[Shepherd777]

Mutated was always better than unmutated until Imbruvica and Venetoclax came along. These two fairly new novel oral agents became a real game changer leaving the mutated versus unmutated question basically a no burger.

I realize that there are some other details undetected so far, but deep in the genome that determine on occasion that a 13q patient responds to nothing and on the other hand a small number of 17P TP53 patients stay in watch and wait for 10 years or more. However for the most part even unmutated Trisomy 12, 11Q and even 17P respond positively to these new agents.

[Tton46]

Thank you !

[MaxSmart]

On the Dr. Lamanna video she also talks about the fitness level of the patient. On this forum we discuss medical markers and not that much about fitness levels, but that factor can make a big difference.

[bennevisplace]

As I understand it BTK inhibitors have good synergy with BCL2 inhibitors. See phase 2 study on high-risk patients of Ibrutinib-Venetoclax as first line therapy nejm.org/doi/full/10.1056/N...

[17Pisme]

Being a 17P/TP53 and having been on I for 4 years I can confirm that both I & V somewhat flattens the CLL field. However, as was expected, I ran out of gas with I & switched to V which has been great & without the side effects (bleeding face, skin rashes, staph infections, etc.).

[hanskloss]

I am unmutated and on Venatoclax for 3 years. Doing very well and hope this continues...never been on BTK...

[Tapps]

Unmutated patients have to be aware of their treatment requirements. The new BTK seem be fairing well for Unmutated patients.