Acalabrutinib

[Motoli]

When is the approval of acalabrutinib for front line treatment of CLL expected? Will it happen in 2019? thanks

[cllady01 Former Volunteer]

Motoli, I would assume when all the trials/studies for its use in CLL as frontline treatment are completed. This is in the U.S. and the approval has to come through the FDA which, hopefully, has requirements that must be met. Hard to predict timing.

Here is a Jan. 2019 update on some outcomes and a statement of looking forward to seeing more trial/study results:

lymphomanewstoday.com/2019/...

[Motoli in reply to cllady01]

That applies to any drug, obviously. Anybody has more specific information? I think the crucial trial is one where acalabrutinib with obinutuzumab is being compared with chlorambucil+obinutuzumab. The last report had indicated that median PFS had not been reached for any of the two treatments. I read that perhaps one year ago, but cannot recall the source or any updates. Comments?

Thanks.

[Cllcanada Top Poster CURE Hero in reply to Motoli]

Its not approved second line yet in CLL, in the U.S. but is available off label. I think we will see second line use expanded to CLL later this year, firstline probably not to 2020, or beyond.

This major Phase 3 trial is just announced and I suspect it will be the pivotal trial for approval, AZ is not very forthcoming...

clinicaltrials.gov/ct2/show...

~chris 🇨🇦

[MFThorses]

I had an appointment yesterday with Jennifer Brown at Dana-Farber and she said 6-9 months, we will see.

[Smakwater in reply to MFThorses]

WoW!

That is a Good indicator!

[Cancare]

First time posting. Thank you all for sharing of resource, knowledge and experience.

I was diagnosed in December. My oncologist appealed to insurance and got the acalabutinib/ Calquence approved. The first couple days I felt really good The two weeks since , the fatigue has set in. No other side effects so far. No headaches or diareah. Loving that there is no caustic chemo IV I got my shingrix I will get myflu shot. Oncologist warned white cell count will sky rocket and level out at 4 months. If all goes as expected all numbers will level at that point. I will keep y’all posted.

[nvp815]

My doctor was able to get it for me off-label and approved by my insurance company. I could not take ibrutinib because of bleeding issues. I wasn't front line so that may play into your approval, but certainly worth looking into. Acalabruitinib has been a game changer for me.

Best of luck,

Nan

[ReneeSusan in reply to nvp815]

Nan, I may start acalabrutinib very soon, but worried about side effects. It seems bleeding and afib is also a concern this drug. I was disappointed to learn because I asked my doctor to put me on this over ibrutinib. How bad is the fatigue? I am 65 and still working and dealing with fatigue now. Wonder how much worse it is? I also learned that wait gain, hair loss and shattered nails are side effects. Have you had any of these? This would be my 4th treatment.

[nvp815 in reply to ReneeSusan]

Hi Renee, From my personal experience, I had many more side effects with ibrutinib. I was only on it for 10 days. I am also on blood thinners as a result of blots clots in my lungs/legs. The combo of the ibrutinib and the blood thinners caused a significant amount of blood in my urine. My doctor was concerned enough to stop the ibrutinib. I was then on a clinical trial drug after that called TGR1202. That only worked for about 10 months and then my CLL got really out of control. That is when I started the acalabrutinib. I have had no bleeding issues with it (even though I am still on blood thinners). I have gained some weight but most of it was weight I lost when my CLL was really running wild. I went from 133 pounds to 118 pounds at that time. Since I started acalabrutinib in January 2018 I gained back all the weight I had lost plus another 3 pounds. So it hasn't been that bad. I don't have any other side effects. With the ibrutinib I was having joint pain, but no joint issues with acala. I haven't lost any hair at all. My fatigue is much improved. I run a small business from my home and work well over 40 hours a week with no problems. If you have a similar experience to me, I think you are going to love acala. My labs have been completely normal for months now. I do still have some issues with my IgG levels, so I get IVIG every 4-6 weeks, but that has been an issue for a while and totally unrelated to the acala. Please let me know how things go for you and if you have any other questions.

Take good care,

Nan

[ReneeSusan in reply to nvp815]

Thanks Nan, thank you for sharing your experience. It is very helpful for me and Let’s me know I made the right choice. I would prefer to go back on Venetoclax, but it tanked my immune system and i had constant diarrhea. But it got the SLL in remission. I am SLL unmutated and have been treat 3 times in 11 years. My blood is not the issue, it’s the pesky lymph nodes and fatigue that keep coming back. Going for biopsy on 4/29. If I need treatment again, my doc reluctantly agreed to put me on acala because I am very concerned about ibrutinib’s side effects. I hope my journey is as smooth as yours if I need acala. May I ask, do you take 100mgs twice a day? They had to reduce the Ven dose from400 to 100 mgs. So zIm wondering if they can start me on a lower dose and titrate up if I need it. I wish you continued good health!

Renee

[nvp815 in reply to ReneeSusan]

Yes Renee, I take 100 mg twice a day. I know that venetoclax can be really tough on your neutrophils. That has not been my experience on acala. I had a problem with my neutrophil count the whole time I was on TGR1202 and had to give myself injections often to increase my neutrophil count. It did not take long at all for my neutrophil count to stabilize while on acala. I had huge nodes everywhere (I have 11q deletion/unmutated). I could not believe how quickly my nodes went away. Within a week or two, I had no palpable lymph nodes. It is truly amazing. This is the best I have felt in years. I have my fingers crossed for you that it all works out and that you have a great response. If you can, I would try to start out with the full dose of acala at 100 mg twice a day. I remember reading somewhere that because of its half-life that it is more effective to take it that way. I know we are all different and our bodies react in different ways, but I am super sensitive to medications and I have to say I tolerate this medication really well. I remember the first week, I felt tired and had a headache, but that quickly resolved. I kept waiting for the nodes to come back and to start feeling crappy again...but so far all is good. I will be anxious to hear how things go for you. Best of luck with your biopsy on the 29th. Sending good vibes your way!!

[ReneeSusan in reply to nvp815]

Thanks for the great advice. So glad your journey has been uneventful. I’ll keep you posted on biopsy outcome. Happy Easter

[ReneeSusan in reply to nvp815]

Nan, do you know if there is financial assistance from the drug company for acala when you are on Medicare? I will be retiring in 8 months. Now I have commercial insurance and a co-pay card which will cover all, but that will not be the case soon and I'm concerned. I don't want to start the drug if I can't continue it when I retire because the cost will bankrupt us quickly. I know we are all in the same boat so just wondering if you been down this road yet?

[nvp815 in reply to ReneeSusan]

That is a really good question. I have several years to go before being in that situation so I am not sure. With my commercial insurance I also have a copay card so the medication costs me nothing. You can check with Astra Zeneca directly or see if the pharmacist who works with your oncology group can help you. My practice has an awesome pharmacist who filled out all the necessary paperwork for me with AZ so I did not have to do anything. I have an appointment this Thursday with my group so I will ask them if they are aware of any assistance once on Medicare. It is scary to think once we reach 65 the help stops!! You also can check with Leukemia and Lymphoma Society to see if they can help in any way. I will let you know what my doctor says on Thursday.

[Motoli]

Thanks to all that I have been commenting. Very helpful information!!

[tryandtry]

I, too, got "off-label" approval, but I had documented experience of several side-effect problems with Imbrutinib. However, Calquence has been very good, so far (9 mos), so worth a try, IMO.

As far as timing, who knows? - but Chris (CLLcanada) knows more about CLL than most (if not all) of us will ever know, so I'd go with his educated estimate.

Gary

[Hidden]

In my opinion, Acalabrutinib should have been FDA approved in December 2015 when the first trial results were released. Here is some trivia. Dr. Maria Fardis oversaw the development of Ibrutinib at Pharmacyclics and then went to work for Acerta where she oversaw the development of Acalabrutinib.

I have been on the drug since February 2015. I have been able to live a normal life without the problems brought on by CLL/SLL.