Is the combination of Imbrutinib and Venetoclax still in trial? Do you have to be in a trial to combine the two?

[kathymac52]

My husband started Imbrutinib just 3 months ago, but there was no discussion about Venetoclax as added in. His numbers are nearing normal and he has had minor side effects. We are grateful for that. However, I have been reading that others are getting great (unbelievable) results with the combination. We live in the US, and this is his second treatment. He started out with BR but it was ineffective as he became severely neutropenic. He is 11q deleted...perhaps that is why?

[MartiP2009]

I was on Imbruvica for 4 yrs in remission for nearly all that time, little to no side effects but last couple of months things started going south and the CLL is progressing. I will start Venetoclax by itself on Monday hoping no side effects and go in remission again. This is the fourth time since 2009 I relapse.

[kathymac52 in reply to MartiP2009]

Thank you for your reply....this is my husband's second treatment after BR chemo.....hoping for the best,,,,but reading the research about I and V and it it s exciting...

[Cllcanada Top Poster CURE Hero]

Venclexta (venetoclax) in combination with ibrutinib are currently in a number of clinical trials... it would not be added to Imbruvica (ibrutinib) outside a trial, except in very rare end of life situations, I suspect.

If the ibrutinib is working well then don't change it... however should it fail there are options with Imbruvica (ibrutinib) and venetoclax etc. or perhaps venetoclax and rituxan, in second line, in the U.S.

Here are the current Veneto/ Imbruvica (ibrutinib) trials

clinicaltrials.gov/ct2/resu...

[kathymac52 in reply to Cllcanada]

Thank you so much.....as Dr. Kaufmann says "smart patients get smart care." My husband does not do the research...too much for him....leaves it to me....just want to be on the cutting edge of treatment as he has an aggressive form of CLL

[Lola69 in reply to kathymac52]

Wonder what that is supposed to mean” smart patients get smart care...”

what happens to the ones that don’t research?

[MsLockYourPosts Passed Volunteer in reply to Lola69]

Hopefully they have smart doctors! Being “smart” doesn’t necessarily mean that you do lots of research. It can mean finding a specialist, asking lots of questions, and getting a second opinion if you are not comfortable with what you are being told, or just want a confirmation that you are on the right track.

[Lola69 in reply to MsLockYourPosts]

A smart doctor asks questions ..

[closh in reply to Lola69]

In my case, I would have had treatment that wasn't the most suitable (FCR for unmutated IGHV).

A really good doctor will make sure you get the best care irrespective of your knowledge but a lot of them are not as up to date on CLL as many patients on this forum.

Graham

[Fant1924 in reply to Cllcanada]

Is there a Venetoclax Rituximab protocol available that specifies a schedule for the two meds?

Dennis, 71, Ibrutinib

[81ue in reply to Cllcanada]

What CLLcanada says is exactly what my dr office told me when I asked to combine the drugs (my thinking is to get rid of cancer now and blast it with drugs). Dr. office says continue on imbruvica if it is working, and if it fails then consider imbruvica and venetoclax - they don't want me to run out of options for future, they think keeping treatments in reserve is a better course to have for a future .

[Hidden]

Kathy,

I have no information to give you but I am so so so super happy to hear things are going well for your husband. Please give him my regards.

Scott

[kathymac52 in reply to Hidden]

Sure will......I share your posts with him, and he laughs along with me....says he wishes we were closer so we could have you and Renee over for dinner and drinks! (He is currently doing NA beer....but I am still doing martinis...LOL)

[Hidden in reply to kathymac52]

I am not a big drinker...I can't take the hang over. I save it for things like Las Vegas...where I drink a lot. When Renee and I were first together she knew I didn't drink much and when we went to CA and hung out with her law skool friends she told me "Don't try to keep up drinking with them, they are pro's" And I said "I will be the last man standing....and after a bunch of Jagermeister and Goldchlager I was indeed the last man standing....barely. Then, cause I was young and in love, I got up after 4 hours of sleep and fixed a clothes dryer that her friends said hadn't worked in a year....another of the many impressive talents Renee has been fooled by into loving me :)))

[kathymac52 in reply to Hidden]

great story....and anyone who can fix a clothes dryer is impressive in my book.....I am Irish, and have a good capacity for drinking!! Don't do as much anymore...but still enjoy my cocktails!!

[Hidden in reply to kathymac52]

For me it makes no difference if I have one drink or ten, I get the same hang over...so I save it for when ten is OK.

[JR1964]

Kathy, I see Dr. Weirda at MDA. He is very high on this combo and to the point that somewhere may a cure be. He also talked of different variations of both drugs and having less side effects on patients. It is wonderful he is doing well on Imbrutinib. There are many things happening. If he does start not to do well there are many options. Have FAITH and BELIEVE- STAY STRONG J.R

[DaleFL in reply to JR1964]

Thank you for sharing this info. I have a lot of respect for Dr Weird. He is very knowledgeable. Even Dr. Furman, who I also have a lot of respect for, is warming up to the ibrutinib/venetoclax combo.

[JR1964 in reply to DaleFL]

Dale, a number of people are very interested in the I/V trials. I am sure it will be a game changer for many. There are also many interested in the upcoming clinical trials of the DNA vaccine that will be at MDA. I just wish that even though things are moving quickly, that this progress could have been done like YESTERDAY. I step back in time to the early 20th century and a doctor with a vision that was ignored- Dr. William Coley. It would be no telling where we would have been and the lives saved. But we still must have FAITH and BELIEVE. STAY STRONG J.R

[DaleFL in reply to JR1964]

I agree with you. Thank you for sharing. I am having a tough day with my CLL-related fatigue and your posts remind me that there is hope for a better tomorrow. Thank you so much.

[JR1964 in reply to DaleFL]

Dale, sorry to hear you are having a tough day. There will be BETTER days ahead. I have told several people this and I will tell you. There is so much advancement going on and through the field of Leukemia that I know it will shake the tree of treatment for all of cancer. STAY STRONG J.R

[DaleFL in reply to JR1964]

Thank you. I know the advances are coming. Novel combinations, more novel agents, new antibodies targeting the cancer cells, vaccines, and CAR-T Cell are among them. I don't want the research to stop until there is a cure for ALL of us. Also, I hope the research community develops a way to cure this disease upon diagnosis.

I am so grateful to you and everyone in this forum who have given knowledge, hope, comfort, and courage. I have to say that this group rocks! I have learned more about CLL than my local oncologist, which is why I am so happy to have CLL specialist.

[Hidden in reply to DaleFL]

Dale,

I too suffer from extreme fatigue. Most days I would give up hope for a cure in exchange for anything to get rid of this fatigue/apathy....and be happy with treatment. The fatigue has taken half of my life from me already....and it has been bad this week for me. As bad as it gets

[kathymac52 in reply to Hidden]

Oh Scott.....I wish I could bear your fatigue for at least one day for you.......and I would hope that treatment starts soon as this sounds like it is time....

[Hidden in reply to kathymac52]

Kathy,

That is the problem...my numbers/symptoms just do not suggest treatment. I argued and begged my Hematologist for treatment the first 6 months because of the fatigue...she brought me over to her side of not one second before I need it...still

I just started the process of trying to get to see Dr. Lamanna in NYC as a CLL specialist because of the fatigue. I don't think there is much to be done about it but maybe she has answers my primary and hematologist don't. I just got to get my insurance to approve a way out of network thing...that is iffy at this point but my doctors are on board with fighting for it.

[kathymac52 in reply to Hidden]

Okay......I am going to hope that the idea of quality of life will convince them that the numbers can lie......that treatment is what you need......perhaps someone on this website can give you direction?

[kathymac52 in reply to DaleFL]

Hang in there Dale....prayers and hope sent out to you.....as you weather this storm.

[closh in reply to DaleFL]

Dale

The Christmas before I started treatment I spent with my family at a beach house we'd rented. I had tonsillitis that knocked me around so badly I could only just manage to walk to the beach, could hardly eat or drink and had to spend a bunch of time in bed.

Two months after that I started taking Ibrutinib and improved within weeks. Now 2 years later, after a course of Ibrutinib + Venetoclax, I feel fine and can do anything. The comment at my last checkup was that "there's no evidence of any Leukaemia".

Hang in there. If I+V isn't the answer, it's probably a good solution in the meanwhile, as is Ibrutinib on its own.

Graham

[kathymac52 in reply to JR1964]

I know!! I am very high on this combo as well......and am frustrated my husband can't have this treatment as they have great results....I do have a strong faith....and believe that my husband will benefit from all this research!

[kimiD]

Hi Kathy.

At my last visit with Dr. Weirda I requested to have Venetoclax added to my ibrutinib off trial. He seemed puzzled at first like no one had asked this before. He explained that since I am doing so well on ibrutinib he would like to "save" the Venetoclax as an option in case the ibrutinib stops working for me. I was disappointed, but he's the expert and I have complete trust in his opinion. After doing some research on my insurance plan, it lists Venetoclax as an approved drug on the formulary, at the same level as the ibrutinib. What it didn't say is whether they would pay for both drugs at once.

From my understanding there is not enough data from the I+V trial to determine whether it can give us complete remission so we're able to come off meds completely. If and when that data is released, i plan to ask again. In the meantime, we can ride the ibrutinib train together.

Kim

[kathymac52 in reply to kimiD]

thank you so much for your info.....I am going to keep plugging away at my doctor to make sure (if and when it is available) that my husband gets this miracle drug as well

[Corkyrissa]

So happy to hear your husband is doing well. I’m on ibrutinib almost one year. Doing well myself. Great to know that if ibrutinib stops working there are other meds we can take. God Bless

[kathymac52 in reply to Corkyrissa]

right.....just want to make sure that my husband gets the best treatment....We live in a small town, and seek advice from a lovely hematologist in a cancer clinic and a CLL specialist in a larger city....just want to make sure he is getting the best care possible.

[milliehf]

Hello kathymac52,

You are correct the phase 2 trial for ventoclax and ibrutinib in MCL patients was published March 29, 2018 in NEJM showing remarkable results. Also good results for combination in CLL treatment. Just checked on ventoclax and it is approved for CLL and SLL in combination with rituxan, however, to date, I do not see FDA approval for ventoclax and ibrutinib in either CLL nor MCL.

[Hoffy]

The V plus I trial I am in is called Captivate via Pharmacyclics. You can call and ask if any are open for your situation. Probably not likely but others may be opening for your need.

Doctors sometimes can request Venetoclax off label and get approval then just start taking both. Or switch to Venetoclax and have some over lap. Get approved for Venetoclax but build up Imbruvica before switching.

Be well ,

Hoffy.

[kathymac52 in reply to Hoffy]

Thank you for the information....I do appreciate all your insight.

[Hoffy]

The V plus I combo has worked very well for me so far !

See my posted.

Hoffy.

[cajunjeff]

I am on ibrutinib single agent as well and have the same question about adding venetoclax. I think its a two part question.

The first question is whether it's a good idea your doctor would approve. That depends on your doctor. I think there is already enough data to know in the short term I plus V is a spectacular combo. People are achieving mrd negative rates so rapidly some doctors suspect these remissions will exceed FCR remissions. FCR arguably cures some folks, so I plus V could be curing folks as well. I do like the idea of having venetoclax as a fall back drug, but if it gave me a shot in combo with I to cure me, I would do it. I asked my doc (Keating) what my fallback plan would be if I failed I plus V and he said their would be other options, including car-nk.

I am pretty sure Keating's plan for me is to add something to my ibrutinib in the future, venetoclax seems the most likely option but he is high on the vaccine as well. I plan on asking him in a few weeks. My guess is for the time begin I will stay on ibrutinib only while they get more data on the possible add-ons for me.

The second question is will insurance companies pay for us to add venetoclax or would we actually have to fail ibrutinib first. I have asked that question a few times and have not gotten a sound answer. The selling point to me for my insurer would be that I could get off both drugs if i got mrd negative.

People are getting into remissions on the I-V combo at high rates and some are stopping all meds. In five years or so we will know how durable these remissions look.

[kathymac52 in reply to cajunjeff]

Thank you! Great analysis and will pose these questions when we see the doctor next week.

[Hoffy in reply to cajunjeff]

Good point. The vaccine sounds very exciting as well as the car – nk.

I personally know someone who did the car – nk and has had very good results without major side effects from the treatment.

[Mlock1962]

Dear Kathy

I am new to this forum, 62 yo male, caucasian, have had Marginal Zone Lymphoma for around 5 years, live in Melbourne, Australia. I have just started a 13 month trial that combines Ibrutinib and Venetoclax, the trial is conducted by Peter MacCallum Cancer Centre here in Melbourne. We start off on 560mg Ibrutinib then in week 5 Venetoclax is introduced, just 20mg to start off with and gradually increasing to 400mg. I am only in week 3 and had no problems with Ibrutinib until a couple of days ago and and am now experiencing muscle and joint pain. I am feeling better already, a growth I had on my jaw has already shrunk, so I will put up with the muscle and joint pain and hope this goes away after a few months. From what I have read on other threads, this is a fairly common side effect and does ease over time. To answer your question, here in Australia you would need to be on a clinical trial to be combining the two drugs. Venetoclax is still considered an experimental drug in Australia whereas Ibrutinib has already been approved for our Pharmaceutical Benefits Scheme (PBS).

Regards, Paul