Hi everyone this is my first post.
I'm looking for some advice, reassurance please.
I'm tp53 mutated and have been on ibrutinib 7 months, which is not working.I saw my consultant on Thursday and the plan is to continue for another 3 months to see if it starts working. My lymphocytes remain at 300.
Has anyone else experienced this problem?Could anyone offer any advice please?
I'm quite worried
Thank you
Hello,
This is just my experience, but several months into Ibrutinib they thought I was also resistant, it turned out to be a bad sinus infection and a course of Azithromycin cleared it up and I continued with Ibrutinib. But don’t despair as I was told Venetoclax was plan B and you may also be eligible for Acalabrutib.
Hope you find an answer.
Colette
Thank you for your reply.Did you start venetoclax?
He said Acalabrutib isn't a option
Gill
Hi Gill,
No the antibiotics cleared the infection so I am still on Ibrutinib. Was there a reason for saying Acalabrutib isn’t an option ? Above my pay grade but I do know it is being given by the drug company during the pandemic, so may be worth asking next time you speak to your consultant.
Colette
when you say not working . what is the trend?
Hi Smith123456,
My lymphocytes were 160 at the start of treatment in February. When I started Ibrutinib they went upto 300 which I understand that happens.
But I thought they would have started coming back down by now.But they haven't moved, just remain at around 300.
All my other blood counts appear within the normal range now.
Hello Redd. I am assuming ibrutinib was not your first treatment. It usually works as a first time treatment for most people.
There are options after ibrutinib. The most obvious is venetoclax, a very powerful inhibitor. Some people take venetoclax in combination with obinutuzimab (Gazyva).
Ibrutinib and acalabrutinib are both covalent binding btk inhibitors. Since they both work the same way, if one does not work, the other usually will not work either. So I don’t see acalabrutinib as an option.
There are ongoing clinical trials for some non covalent binding btk inhibitor drugs. In theory these drugs can work where covalent binding btks do not. So you can ask if any trial like this is going on in your area.
Idelalisib and duvelisib are yet another type inhibitor that work differently than ibrutinib and venetoclax. That might be an option.
I think the other big option beyond other inhibitor drugs would be a trial for CARnk or CAR-T therapy. Dr Brian Koffman who posts on here has an excellent blog about his experience with CAR T.
Among those options, I would think venetoclax would be first up. You need to discuss your options with your doctor, but you do have options. I would want to know about clinical trials in you area if I were you, particularly any clinical trial involving venetoclax in combination with other drugs.
Hello Calunjeff
Yes Ibrutinib was my first treatment.
Is it because I am Tp53 mutated that it's not working?I don't really understand.
He mentioned he would start me on another drug in 3 months if this is still not working.
I cant remember what he said but it was none of the drugs you have mentioned.
He said there was a strong chance it could cause tumour lysis syndrome , so then I went into panic mode!
I am going to ring and talk with my Macmillan specialist nurse tomorrow and ask her the name of the drug.
Thank you for your reply.
I'm not a anxious person but I am at the moment!
Redd, Ibrutinib is a btk inhibitor. Btk is an enzyme found in Cll cells in a greater amount than necessary and it helps keep Cll cells alive. Ibrutinib binds to the btk on the cell, allowing it to die.
Resistance to ibrutinib as a first treatment is not common, but does happen. It’s not directly caused by TP53 but rather due to mutations found in other genes in the btk pathway. The two mutations that are suspected of causing ibrutinib resistance are to the btk and PLCy2 genes. People with 17p Cll can be more likely to acquire mutations like this so the TP53 could be indirectly related. It’s not directly related because ibrutinib does treat 17p Cll effectively in some people
Tumor lysis syndrome (TLS) is known to occur with venetoclax because venetoclax is so efficient at killing Cll, the waste product of the dead cells can overwhelm us. There are strategies to deal with TLS such as debulking Cll with other drugs before using venetoclax and giving small doses of venetoclax at first with close monitoring. The fact your doctor brought up TLS makes me think he is considering venetoclax (venclexta) for you. Venetoclax is the most common drug used after ibrutinib stops working.
Venetoclax is an oral drug and works great He might even keep you on Ibrutinib too, sometimes Ibrutinib can be partially effective and still confer some benefit. Or your doctor might be considering other drugs too, you have options which is good
Reddg, we can't assume anything about CLL and treatment , each of us is so different, and the details of our particular CLL are specific to us and we are medically untrained).
It is not easy to say with our limited information (we are not medically trained) at what point your lymphocytes should begin to decrease. How are you feeling? Are you noticing any other symptoms? It would appear from what you have related the lymphocytosis is asymptomatic.
I do not want you to doubt your CLL provider without some basis to do so, but do you know how much experience your Dr. has with CLL patients and with Ibrutinib?
You seem to have had a conversation with your Dr. and the Dr. is recommending a bit more time--I would think that is to get a further reading on your bloodwork.
If you are uneasy, it would be helpful for you to have a conversation with your Dr. about your worries and anxiety. Those feelings are not unusual for patients starting a new regime, so don't beat yourself up about having them. But please do talk to the Dr or his RN about your concerns. And, if you can do so safely in this weird time in which we live
take a walk as many days as you can to help with worrys--it really does help.
Best wishes with getting some assurance and in having the Ibrutinib
Hello cllady01
Thank you very much for your advice.
I will ring my Macmillan nurse at the hospital on Monday and have a talk with her.Im just feeling more tired than I normally would.
I dont know how much experience the consultant has with cll and Ibrutinib.
Because we are a small hospital he will see all the acute and chronic leukaemia.
Plus any other blood related problem I'm guessing
Check out this information from a previous reply of ( see AussieNeil )
Ibrutinib
Ibrutinib 
Ibrutinib
Ibrutinib
