I am a 78 year old male living in the UK. Started treatment 3 years ago. Had two rounds of FCR which was stopped due to my bone marrow being wrecked. Managed to get on to Ibrutinib as a named patient via Dr Anna Schuh in Oxford. Now under the care of my local haematology consultant in Hereford. After 21 months on Ibrutinib which quite quickly got my blood results back in normal range, my kidney function started to deteriorate and my consultant stopped the Ibrutinib. My bloods continued to be in normal range for 8 or 9 months without any treatment and I have felt well.
However, my last 3 monthly blood tests have shown my white blood count and lymphocytes rising - now 23.7k and 17.9 respectively. I believe I am heading for treatment again. My question is, what drug would be appropriate bearing in mind, my poor kidney function ? Venetoclax ?
David.
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Hi David, I don't know the answer and it must be difficult because of the kidney function. There is an article on Cll Society today about new options and Dr. Mato from UPenn will be speaking tomorrow night on new options. Hopefully that video will be available.
Hi David- I am currently reading through this board because we just lost my father-in-law (age 62) and I am just looking to understand. I can tell you that he was on imbruvica for a couple years. He did have a stem cell transplant almost 4 years ago, ended up getting sick again and was put on imbruvica, which to us was a miracle drug for quite sometime. In February he was told that through his scans and biopsy that the cancer was coming back and that imbruvica stopped working. He was brought to the hospital to start venetoclax and was suppose to be in for observation only for a few days. In that time, his liver levels were elevated and they could not figure out what was going on. From there they took him off of venetoclax, gave him a round of retuxin, and at some point he ended up with TLS. The moved him to ICU for an infection (we are still foggy on the details) and that was pretty much it. When he went into the hospital he felt as well as he had in like ever. Seemed as strong as ever which made this very shocking to all of us. According to his doctor, studies seem to have pretty dismal results when imbruvica stops working (that is the info I am looking for now as I do not understand why he would not have said this before. Originally he was saying that the venetoclax has a 90% chance of working and that this new research he has done only after my father-in-law passed away). I wish you the best of luck and health. I am in search of answers to the aforementioned things, if you happen to hear anything that might help, please let me know. Thanks.
Sorry to hear that you have just lost your father-in-law and that you've joined to find answers why this happened so suddenly and unexpectedly. Unfortunately, CLL is well characterised as a cancer of the immune system:
healthunlocked.com/cllsuppo... Treatment generally further weakens the immune system by suppressing bone marrow production of the most common white blood cells called neutrophils, which are needed to fight bacterial infections. Both Rituximab and Venetoclax are well know to cause this side effect (neutropenia). Normally new neutrophils only survive for a few days to a week in the blood, so when bone marrow production stops, neutropenia can develop quickly and without any symptoms. Unless detected by a blood test, the first you know of it is when you become ill.
Early trial findings showed those stopping Ibrutinib didn't do well long term, but more recent studies have thankfully shown the situation isn't as bad as initially thought: healthunlocked.com/cllsuppo...
As with all cancers, the CLL cells find their ways around new drugs, so they become less effective, eventually ceasing to work. Genetic testing is able to identify most, but not all patients that are likely to develop Ibrutinib resistance. When that happens, there are a number of alternative drugs which use different mechanisms to tackle CLL, so switching to an alternative treatment has a high likelihood of working, as you were correctly informed and was done in your father-in-law's case.
Venetoclax is a very powerful drug and is able to quickly kill off so many CLL cells that the potassium released from inside the dying cells can push up blood potassium levels sufficiently to stop the heart, causing sudden death from what's termed Tumour Lysis Syndrome (TLS). Because several clinical trial patients died on Venetoclax from TLS, the trial was stopped until a change in protocol was introduced, which required patients at risk of TLS stay in hospital during dose escalation for close monitoring.
Given your father-in-law was in hospital when he developed TLS, it should have been controlled (by taking him off Venetoclax and administering allopurinol), I presume it was an infection that was the cause of his death. We all harbour bacteria, viruses and fungi that when healthy, our immune systems can keep under control. Sadly, when neutropenia develops, those bugs can gain the upper hand and quickly become deadly, particularly if an infection gets into the blood and what's termed neutropenic sepsis develops. Sadly, that's of little comfort to you and your family right now, but it's something all of us with CLL face, with infections being the most common cause of death.
I hope that this helps you and yours come to terms with your father-in-law's untimely death. You'll all still be working through the grieving process, so just take the time you all need and know that you'll be able to find support from people who understand what you are going through in our community.
Neil- you know your stuff. The cause of death was Septic Shock. We are finding that communication wasn't as strong as we would have liked so we are still trying to figure this all out, but he was moved to the ICU maybe 9 days into his stay and at that point the nurse told my husband that his dad's port was infected. Would that be the type of infection that would cause someone to go into septic shock, would that have been the TLS, or can both cause that? In research I have found TLS and infections both listed as the top risk factors and I was wondering if they are related.
I do appreciate the help. We are hoping to get his records and have someone go over them with us as well as there are just so many unanswered questions and I just feel having the answers would help us to start moving forward. Even at one point he was telling me they put a port in and I was questioning why. He said that the nurses were having a hard time getting blood drawn from his arm (and yet he has tests run all the time where they do this) and so they thought the port would be easier. It is just all along the way things went from 0 to 100 and while I recognize now that could have (should have) been expected, even when my husband spoke to the doctor before this, that was never the expectation that was set up. That being said, it is just really difficult to understand. Thanks again.
Sadly, I'd say the infection from your father's port got into his blood, where it can be difficult to treat. If not promptly treated with effective IV antibiotics, sepsis can develop, which can prove quickly fatal as you sadly found out. I don't think TLS would be implicated, other than perhaps weakening your father in law's health so that maybe he was less fit to fight the infection. (I'm not medically trained, but have been living with neutropenia for 8 years due to my CLL infiltrating my bone marrow, so I've had a few hospital admissions to counter sepsis developing.)
Our bodies rely on our skin maintaining a barrier against infections, with neutrophils first responders via the blood supply to any bacteria breaching that barrier. Any time that barrier is punctured, there's a risk of bacteria entering and rapidly multiplying and in hospitals, there's the risk of those bacteria being antibiotic resistant. If an infection develops, it can take some critical time before it becomes apparent that an antibiotic is not working and an alternative is needed.
Ports are a trade off between frequent venal punctures (each with their own risk of infection, plus making the veins harder to use in the future) and a greater risk of infection from having just the one port in place. In your father-in-law's case, nurses had the additional challenge of difficult blood draws, so I can appreciate why they installed the port to save your father-in-law the discomfort of multiple attempts to get a blood draw, save his veins and also to ensure accurate blood draws. Blood testing is a critical means of monitoring for TLS management. (It's a fact that difficult blood draws can result in inaccurate test results. A difficult draw causes broken blood cells, with their cellular contents released into the blood serum, falsely increasing some critical measurements, where having an incorrect result could potentially cause incorrect treatment.)
Thanks, Kim. Very sorry to hear your story. I am just learning that Venetoclax can cause some problems. I may avoid it. Every patient is different which makes things difficult. All the best, David.
I failed ibrutinib due to side effects, and moved on to Idelalisib and rituxan, which should be available to you in the UK.
It has been side effect free for me, other than occasional colitis. There are a number of prophelactic drugs required on Zydelig (idelalisib), and liver toxicity needs to be monitored... kidneys seem not to be an issue and allopurinol is used to prevent tumor lysis...
Venetoclax has very narrow use at the moment and I don't believe it is available on the NHS, but is being considered for early access... I think limited to 17p deleted, but you will need to discuss this with your doctor.
My absolute lymphocyte count [ALC] was in the 40K region when quitting ibrutinib, and I wasn't treated with Zydelig (idelalisib) until my Hgb tanked and my absolute lymphocyte count [ALC] was over 370k.
So depending how you feel treatment might be some time off...
From Abbvie
The UK Medicines and Healthcare products Regulatory Agency (MHRA) has looked at the scientific evidence for venetoclax in CLL patients with a hard-to-treat form of the disease, and concluded the drug should be included in the Early Access to Medicines Scheme (EAMS).
Having spoken to my consultant today, my understanding is that although venetoclax has yet to be approved for regular NHS prescription, it is made available to named patients by the manufacturer. So it is possible to get in the UK, in certain circumstances - apparently.
Hi David, trying idelalisib as Chris says seems the next likely option, but can you get a referal back to Oxford to see if any other trials available, also if options are limited look at other centres. Guess you could perhaps also travel to Cardiff or Birmingham. Anyhow, the very best of luck with the searching.
I started Ibrutinib only after failing immuno/chemo therapies FR & RTX respectively which left me with permanent kidney damage. My kidney function was almost bad enough to keep me off the Ibrutinib Clinical Trial which I have now been on for 5yrs and 10 months. I was managed by getting allopurinol and extra IV hydration in the early stage of Ibru use.
Kidneys are complex organs with many flavors of dysfunction and are critical for most types of cancer therapies that kill off our CLL cells - the higher the tumor burden & faster the killing the more we need expert management to avoid kidney damage. I only question the stopping of Ibru since you state you are being managed by a local hematologist who is not likely to be as knowledgeable on CLL to handle complications of the kidney or use of the drug as one would like.
I would be asking the following questions in your situation before giving up on Ibru.
1) Is the kidney issue directly related to Ibru use and has a Nephrologist weighed in on that part of the diagnosis for your kidney deterioration?
2) Has reducing Ibru dosage from 420mg to 280mg been considered? Note: I have been on 280mg for over 5 years and doing very well.
3) If your kidney problems are independent of Ibru what assurance are you being given that another therapy will not be as bad or worse than what you are experiencing on Ibru? Note: I had good kidney function prior to 1st TX but the toxic reaction to Rituxan nearly fast tracked my expiration date.
4) Dehydration is listed as a side effect with patients on Ibru so is it possible you are not adequately hydrating? Can this be addressed?
Certain kidney pathologies can be successfully addressed by Cyclophosphamide and or Rituxan so my comments are to be taken as talking points to cover what might be unfortunate to overlook if Ibru had been successful in dealing with your CLL.
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