Combination therapy with Ibrutinib and Venetoclax?

[kathymac52]

Does anyone know if you can get the combination of Ibrutinib and Venetoclax without being in a trial? We live in the US ( Wisconsin). I am reading that the two together gives a great punch to that CLL. My husband has been on Ibrutinib for 2 months now.

[Cllcanada Top Poster CURE Hero]

Might get it off label, depends on your insurance and how well your doctor can make a case for it.

~chris

[Jm954 Administrator]

I agree with Chris, does he have a complex adverse FISH profile?

[kathymac52 in reply to Jm954]

yes, he has 11q deletion and a positive ZAP 70 was confirmed. He started with the BR therapy, and it reduced his spleen and lymph nodes but he had to quit after only 4 out the 6 infusions because he became severely neutropenic for 5 months....

[johnl]

I have heard of someone getting approved by insurance for venetoclax as a second treatment even tho they weren't 17p deleted, but insurance companies aren't likely to approve both of these expensive drugs together. However, from what I've seen the value of the I in IV is to lessen the tumor lysis in the venetoclax ramp up. So if your on I now and switch to V solo it might have the same effect. Just a thought, but I'm no doctor

john

[closh in reply to johnl]

Hi johnl

The I+V combination trials are because in pre-clinical studies CLL cells were more susceptible to Venetoclax (BCL2 antagonism) while also being treated with Ibrutinib. The trials have been very successful so far - although it's early days - adding Venetoclax after 3 months of Ibrutinib and then using both drugs together for 12 months. It makes sense to me to attack the CLL from multiple directions at the same time to reduce the chance of adverse mutations.

The combo therapy aims to cure CLL, for at least some patients, or to be used episodically with (hopefully) lengthy gaps between treatment. Although it's double the cost of a single drug for 15 months of treatment, it works out cheaper in the long run if patients can skip treatment for at least a couple of years after that. I don't know if insurance companies will feel they have the data to go with that approach yet though.

Graham

[mikec11 in reply to closh]

👏👏👏

[YvesP in reply to closh]

Thank you for info my Dr at CC in Florida want to add Venetoclax to ibrutinib in her estimation I need a boust after 10 months the progress is to slow. Will keep you in the loop. Maybe I+V my equal HOPE 👍

[mikec11]

oncologytube.com/video/fina...

[JigFettler Volunteer]

Not in UK. I asked this very question of one of our super specialists. I was told no. Not for any money. At this time. Reason: insufficient data to support. Only available as a trial.

And then I for 8 weeks for TLS cover before V

Regards

J

[AdrianUK in reply to JigFettler]

Which is one reason why the FLAIR trial is attractive to first liners who buy the “multiple modalities” theory since you have a three in four chance of not getting a monotherapy arm. One of the arms is I+V.

[BJollie]

If anyone is doing I+V off trial please let us know. I’m trying to get my doc to do this, but she says “No one’s doing this off trial & we don’t have enough data yet”

[JigFettler Volunteer in reply to BJollie]

...exactly what I was told. What is on offer in the USA? - if anyone watching from over there!

[BJollie in reply to JigFettler]

Currently, just monothetapy for each

[JigFettler Volunteer in reply to BJollie]

I believe I available privately. Not sure if V is... here in UK.

Using V as monotherapy... How is Tumour Lysis managed?

[E-Lynn]

I am on Venclexta aka Venetoclax and started on 1/24/17. To answer Jig -- TLS is managed by starting with a very low dose and increasing slowly. 25mg --> 400mg. Lots of water to drink.

I question whether you really need the Ibrutinib in the pair. On off-label Venetoclax from Coutre at Stanford, I am now MRD- in my peripheral blood with no side effects except dryer skin.

I am 13q- unmutated, previously on the NIH Ibrutinib trial (2012) but bumped because I developed lung cancer. Then mono Obinutuzumab (2015) and then the Venetoclax in 2017.

[closh in reply to E-Lynn]

TLS was a problem when Venetoclax started off at 50mg and I think there were 2 deaths. This was fixed by dropping the initial dose to 20mg. They're a tiny pill the first week but very effective. I've mentioned before, with my first 20mg my ALC dropped 20K over 7 hours! If patients are considered high risk, they have some of the first doses as an in-patient and this involves very regular TLS monitoring and IV hydration. I don't think TLS is anything to worry too much about so long as you follow the instructions carefully. My non-scientific assumption is that there are probably only so many CLL cells that 20mg of V can bind to.

They expect I+V will lead to more MRD- results that V alone. We'll see - the few people I know on my I+V trial have all reached MRD- in blood and marrow. It's also hoped that the combination will allow people to come off treatment and have a reduced risk of CLL becoming resistant, compared to a single drug.

Hopefully the trial results support approval of this combo soon. By then, we'll all probably want CAR-NK or INVAC-1 though

Graham

[E-Lynn in reply to closh]

Actually, the deaths were during the Phase I trial when they were looking for maximun tolerated doses. The maximum daily dose prior to Randy's death was 800mg. He took 1,200mg and died that night of TLS. All trials stopped and a rethink happened. He had started the trial on very low dose but ..... The story is on CLL Forum where he was posting prior to his death the night he took that last biggest dose.

[kathymac52 in reply to E-Lynn]

Was Randy a relative/husband?

[E-Lynn in reply to kathymac52]

A CLL friend to many. Patient Power was filming his experience and he was very public about his trial experience. Something went terribly wrong and the protocol and respect for Venetoclax or ABT-199 as it was known then increased. Very sad in deed.

[kathymac52 in reply to E-Lynn]

These wonderful pioneers are what is paving the way for so many....RIP Randy and thanks for your sacrifice.

[closh in reply to E-Lynn]

Thanks for clarification E-Lynn. That is a much higher dose than I thought!

We definitely owe gratitude to Randy and those who put everything on the line on those early trials.

[kathymac52 in reply to closh]

Please explain CAR-NK or INVAC-1 please.

[closh in reply to kathymac52]

CAR-NK is a treatment using genetically modified NK (Natural Killer - immune cells) from umbilical cords to attack your CLL cells. It's similar to CAR-T which uses genetically modified T cells taken from your own body but seems to have less side effects (very early days though). The genetic modification makes the cells recognise and target the CLL cells but they may also target other lymphocytes.

INVAC-1 is a vaccine therapy invented in France that gets your immune system to recognise and attack cancer cells. There were stories about it curing solid tumours in about 97% of mice and there's currently a clinical trial for CLL underway in the US.

I can't claim any expertise on either of these but what I do know is there are some really good CLL treatments (like Venetoclax combos) well progressed in trials and even more potentially fantastic ones at early stages.

I bought myself some new ski boots last year because I'm now quite confident I'll get plenty of seasons out of them.

Graham

[kathymac52 in reply to closh]

Thank you so much......and I like your positive attitude! I heard about the trial for the vaccine, and I think it is taking place in California.

[Hoffy]

sometimes doctors can just put in claims for each separately and get each approved

[GG1084GG]

I’m currently on ibrutinib and venclaxta and not in a trial. Just added venclaxta this past Tuesday.

[kathymac52 in reply to GG1084GG]

Is Ventoclax the same as venclaxta? Where are you living? US or UK?