My Haematologist has suggested that I may need to start treatment with these drugs and Calquence. I’ve been on Watch & Wait since diagnosed in 2014 when WBC count was just above normal range. Now it’s about six times higher than normal range and my red cell count has gone just below normal range as have my iron levels. I’m 69 years old and have long term disabilities due to cerebral palsy which impairs my mobility and partial sight. I only have 25 percent of normal vision in one eye only and I’m blind in the other eye. Some years ago one of my eye doctors told me that my corneal graft could be at risk of rejection if I have chemotherapy due to the immune reactions caused by chemo.
I have so far only read some of the booklet about venetoclax and obinotuzimab. I would have to ask the hospital to provide them in large print if I go ahead with the treatment.
I am concerned about the alarming number of possible side effects with these drugs and my Haematologist’s suggestion that if they work I would have to use them for life.
I would like to know if people have experienced side effects on these drugs which have impacted their quality of life and also whether they have been able to stop medication once bloods retuned to normal?
I also don’t want to have to self isolate if I start treatment. I would be grateful for any comments or advice that people can give. I’m unaccustomed to taking any orthodox medicine long term except for eye drops.
I send good wishes to everyone else who posts on this site for your healing.
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tigerbeauty
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There are a few inaccuracies in what you have related, such as:-
- Acalabrutinib (Calquence) + venetoclax + obinutuzumab isn't chemo - all of these drugs are targeted therapies. By targeted, we mean that the drugs target just the CLL and unfortunately healthy B lymphocytes; researchers are still working on distinguishing the cancerous CLL cells ftom healthy B cells, but these drugs tend to leave other body cells pretty much alone
- Acalabrutinib + venetoclax + obinutuzumab or just venetoclax + obinutuzumab are time limited therapies, not forever therapies. Treatment is over in a year or so. Venetoclax plus obinutuzumab, is what I'm fairly sure you meant.
- Acalabrutinib/Calquence is a maintenance treatment used for life, but plenty of our community are on this or a similar treatment and doing well.
- A white blood cell (WBC) count about six times higher than normal range is not a reason to start treatment
- neither is a red cell count just below the normal range
- I can't see how treatment with any of these targeted therapies would put your corneal graft at risk from the drugs, but you would be wise to see your a corneal graft specialist about the impact of the reduction in your immune system inhibition by the removal of your CLL tumour burden. See below: healthunlocked.com/cllsuppo...
The respective triggers for starting treatment from what you have shared, are:-
- a haemoglobin count trending below 100
a lymphocyte count doubling in under 6 months when it's above 30, when there are other indications that you need treatment
I had this (A+V+O) treatment commencing in 2019, reached uMRD during my treatment and have been in remission since finishing treatment in 2021. You would not be given this treatment unless on a clinical trial, so I'm sure you meant "these drugs or Calquence". You would either be assigned Calquence or venetoclax plus obinutuzumab. We have many members with experience of these treatments.
Your immune system is somewhat suppressed when you start treatment, which might yet be some time away unless you have some other trigger for starting treatment. Provided you are up to date with your vaccinations, mask up well, wash your hands carefully, social distance and stick to well ventilated areas where possible, you shouldn't need to self isolate, though you should take extra precautions if your neutrophil count is dangerously low. The pandemic isn't over, so we all need to be taking precautions against COVID-19.
I too have been told I should begin treatment with ventoclax+ibrutinib but haven’t been given a date yet for starting this treatment. I too was concerned with the risk factors associated with this treatment, as well as the quality of life type issues while undergoing a treatment that what seems to require many hours in a hospital like environment early on and long hours thereafter for blood tests, etc. at least once a week thereafter for up to two years. Plus add on a two-hour round trip to the facility doing the treatment/monitoring the progress, etc. Because of all the foregoing I asked my hematologist if there are any alternative treatments and, given the fact that the Ibrutinib I’ve been taking is starting to lose its effectiveness, my hematologist answered “No”. My only other question at that point was to ask her whether treatment could be delayed at least until August 2023, to which she said “yes”. I now wish I would have asked her whether it could be delayed indefinitely subject to future blood test results.
I am 75 years old and have been taking 420 mg of IB since 2014. During the time I’ve been taking IB, my wbc, until recently has remained in the range of 12,000 - 16,000 and my LDH ranged between 240 and 250. (When I started IB in 2014 my wbc was near 300,000). Except for the first couple of years or so on IB as far as I know all of my other blood counts were and still are normal or near normal until recently when my wbc jumped up to 25000 and my LDH rose to 319.
Do you think it would be reasonable if I followed up with my hematologist asking her to delay treatment indefinitely beyond August subject to future blood test results showing a significant further worsening of my blood test results?
If there are no other options and my blood tests require immediate treatment and there are no other reasonable options, I don’t have any problems in starting V+I, but I don’t want to start treatment until it is absolutely necessary given the risk factors and other side effects and lifestyle changes during the 2-year treatment.
The most recent ASH findings indicate a 2 drug regimen, for *one* year, is giving about the same remission depth and length, as the triple treatments or the 2 year V&O, or for being on a BTK indefinitely. So IMO this is where your doc is mentioning V&I, they are on top of the latest research.
Regarding the intensity of testing during V initiation, that is determined by the risk for TLS, which is directly related to your lymphocyte count plus whether or not there are lymph nodes larger than X. There are 3 levels of monitoring recommended, and are based on these numbers (ALC plus node size) plus (IMO) whether or not someone is best served being hospitalized once a week for 2 nights, the first few weeks. This information is in the Venclexta package insert:
If you check out Table 3 on Page 4-5, you will see that the lower level of monitoring is labwork once a week, on the days the doses are increased. Is it a pain to hang around the clinic most of the day? Yes. But it's needed *just in case* ones' CLL is very sensitive to the drug and starts dying immediately. You don't want an easily preventable/treatable TLS!
And there is discussion surrounding "when to treat" since these drugs can cause a dip in other cell lines. The cutoff for *MUST treat when various cell lines drop to X* is pretty clear; the question is how much risk you are willing to take, if some other cell line happens to drop when starting treatment. There's no way to know ahead of time. And IMO giving yourself a bit of leeway, so neuts and RBC's and platelets can drop a bit without something potentially serious happening, is a good idea. Yes there are drugs to stimulate neutrophil and RBC production, and one can get a platelet or blood infusion. But why depend on these? Why not treat a little earlier, so you may not need the extra hassle and side effects of additional medication/clinic visit for blood infusions? If you start before any of the cell lines are at the "danger zone" any dip in values may not need treatment.
And there is some data out that if resistance to a BTK begins, one should add the second agent sooner rather than later. So factor *this* into the decision of how long you want to wait before considering the doublet treatment. And that if you treat when still in Venclexta TLS risk potential low, there is less testing/monitoring involved initially.
I would very much agree with what AussieNiel wrote.
I can only add that I took part in a clinical trial with Ibrutinib+Venetoclax+Obinituzumab in 2020/21. (Acalabrutinib is a newer drug than Ibrutinib, and from what I know is somewhat better than Ibrutinib). This was a 15 month treatment. In my case I ended up uMRD in November 2021, and have been in remission since then.
I'm no doctor, but I think you should do fine with the A+O+V treatment. You should expect good results. In any event, good luck!
Sorry, but I agree with SofiaDeo about why you should not defer treatment too long; you are only going to increase the risk of the very concerns that you have, because your CLL is becoming resistant to the ibrutinib and your nodes and spleen sizes and bone marrow infiltration could be increasing, hence you may need more monitoring for Tumour Lysis Syndrome.
Also, did you mean venetoclax + obinutuzumab, not venetoclax + ibrutinib. I don't see why your specialist would suggest just adding venetoclax when your CLL is becoming resistant to ibrutinib.
Finally, I presume you live in the USA? If so, you could arrange a free video appointment for a second opinion with a CLL specialist through the free CLL Society's Expert Access program, if you haven't previously used this valuable service.
Thank you for the reply. Yes, I meant ventoclax and ibrutinib. And NIH suggested it to me in January and told me not to be surprised at my March appointment if my hematologist recommended it to me. She did. And don't get me wrong, I don't want to wait until I'm at death's door to start the v+i. I don't have any problems with my nodes or spleen and I don't want to wait until I do have such problems before starting the v+i. I just think that my blood work isn't so bad at the present time that I need to start treatment immediately.
Also, when NIH briefed me on v+i, they didn't say I developed an absolute resistance to ibrutinib. (Maybe it's the same thing, but) They only suggested that the ibrutinib has lost some of its effectiveness in me. And the way I understood NIH, they believe that ibrutinib will still provide some additional improvement in my condition, at least at stage 1 of treatment with ventoclax.
We are agreed that you haven't developed absolute resistance to ibrutinib. When ibrutinib resistance develops, it tends to happen slowly as the resistant sub-clone becomes more dominant over time. The NIH has a good reputation for CLL management.
ASH reported on Venclexta and Ibrutinib for 1 year as giving durable remissions similar to V & O 2 year protocol. This is early data, and some triplet studies as well as the standard V&O studies are ongoing, to verify if "oral only for 1 year" remission rate, remains the same if not better than, remission rates for the current therapy recommendations. My specialist gave a presentation a few weeks ago regarding this to our local CLL Society group, and stated he would consider this time limited double oral agent treatment, for patients who would qualify. The problem I see in the US at least, is getting insurances to pay for 2 oral agents at the same time. Ibrutinib was the BTK used in the study, but it seems reasonable that similar results could be expected with acalabrutinib. One would need to argue with/show the costs to the Pharmacy Benefits Manager, where a 1 year treatment would ultimately cost less than "forever" BTK treatment.
SofiaDeo, was the study report on Venclexta and Ibrutinib for patients where the ibrutinib was failing to keep the CLL under control? The reason I questioned why Michael meant V+I and not V+O, was because he mentioned his ibrutinib management appeared to be failing thus: "I am 75 years old and have been taking 420 mg of IB since 2014. During the time I’ve been taking IB, my wbc, until recently has remained in the range of 12,000 - 16,000 and my LDH ranged between 240 and 250. (When I started IB in 2014 my wbc was near 300,000). Except for the first couple of years or so on IB as far as I know all of my other blood counts were and still are normal or near normal until recently when my wbc jumped up to 25000 and my LDH rose to 319."
The rising LDH and higher WBC count indicate a more active disease. Nine years of CLL management on ibrutinib is pretty good.
I will ask when I see him this upcoming week. He was giving a synopsis of ASH findings to non-medical folk in the CLL support group. My impression is that it was a standard study. I know I recall reading about "adding a second agent ASAP when BTK resistance is starting to appear" last year sometime.
Hi Neil, thank you very much for your detailed reply. My Haematologist recommended Acalabrutinib or Venetoclax with Obinutuzimab as his proposed treatment for me in his letter to my GP. I know that these are targeted therapies and not chemotherapy but there is an effect on the immune system during treatment.
My corneal graft was live donor tissue from an Eye Bank. The eye has a degree of immune privilege therefore you can graft donated tissue into it without having to take anti-rejection drugs. The immune privilege is not absolute. What this means is if the immune system is repressed due to cancer treatment there is a risk that when treatment stops and the immune system starts to recover it could recognise my graft as a foreign body and reject it. I would seek updated information about this risk before agreeing to go ahead with treatment. I am due to speak to my Haematologist again in two months time.
Can you tell me what uMRD is, please Neil?
Thank you to everyone else who has responded to my enquiry. I struggle a bit with my phone and laptop due to poor vision so it may take me a bit of time to get back to you but I appreciate that you have responded to me.
I do a huge amount of reading in my role here and I couldn't imagine doing it with poor eyesight. You most definitely do need to take any necessary steps to maintain the eyesight you have.
What you asked was "Some years ago one of my eye doctors told me that my corneal graft could be at risk of rejection if I have chemotherapy due to the immune reactions caused by chemo". You have raised a valid concern about what might happen to your graft when the suppression of your immune system by your CLL is lifted by treatment. It's possible that your CLL has actually reduced your risk of rejection, because of how it drives T cells to exhaustion and reduces the effectiveness of healthy B cell maturation, which is why our immunoglobulin production tends to fall over time. I suspect the immune privilege of corneal grafts is because of the lack of blood supply to the cornea, which is why cornea donations are the only donations accepted from people with CLL to my knowledge. Targeted therapies wipe out all B cells and have only a minor effect on T cell populations. CLL tends to drive an increase in CD8 (cytotoxic) T cells, changing the CD4:CD8 ratio. There is evidence that ibrutinib improves T cell function, which doesn't seem to be the case with other BTKi drugs. I've modified my earlier comment to refer to this more detailed discussion.
uMRD is undetectable measurable residual disease. It's a proxy measurement of the number of CLL cancer cells remaining after treatment that provides an indication of how long our subsequent remission may last when we finish treatment. If less than 1 in 10,000 white blood cells is a CLL cell, then you've achieved uMRD (technically uMRD4, less than 1 in 10^4, or 10,000). As measurement techniques improve, you can be checked for deeper responses; uMRD5, uMRD5.
Caregiver/wife/minion here - I would suggest you have one or two people who will have your back - for visits with the oncologist, for the many blood tests (and streams of results), and water-drinking reminders. We take reasonable precautions but see our grandson all the time and he is definitely our weakest (and most wonderful) link. My husband is not a fan of audiobooks but I know if it was me in that seat, I would be deep into the Scottish Highlands with Hamish Macbeth (or some other police procedural). Good luck to you.
Thank you, Jujy. My partner drives me to all my hospital appointments and accompanies me in the Consultation. Some appointments are held remotely over the phone.
if the Ibrutinib is fading and it's not working well for you, I don't understand why your hematologist doesn't just put you on Venetoclax alone. The obinatuzumab is likely the drug that would be the hardest on you and certainly on your immunity for a year after you're done with it. If Venetoclax after you start, it doesn't give the desired effect they want then they can add those other drugs later.
Venclexta monotherapy is only "approved" for people with del17p/TP53 mutations. So it's not an option unless ones hem/onc is willing to "step out of the box" a bit, assuming they don't have to follow a National or other protocol for treatment options.
So your and theirs hem/onc is willing to "step out of the box". Was this for initial therapy? I bet not. I didn't say it was impossible, just, some docs won't prescribe if it's not in the package insert or recommended in the literature. Especially for initial treatment; most often, a "standard" is tried and docs get creative if/when "standard" stuff fails. Tigerbeauty is in the UK, with a national formulary for drugs as well as treatments, where protocols are often followed more closely than places where there isn't a National Formulary or prescribing protocols. Someone here in the US getting meds from, say, the VA or Kaiser Permanente are in a different boat than those seeing a private hem-onc. Not to mention how much a stickler their insurance company will be for following FDA recommendations and what the literature recommends. There's at least one person here who had a problem with their US insurance company arguing with their world-renowned CLL specialist recommending a standard protocol for initial therapy.
This is my second treatment. I had Ibrutinib four years ago. I stopped it after a year. I didn't like it because it gave me higher blood pressure, a fib, and made me tired all the time.
Sorry to hear of your predicament. I’ve been on almost dozen chemo drugs, but not those two so I regret I am not able to comment. Get a second and third opinion for advice and research it best you can. Good luck!
Thank you, LarryK. Because I have other conditions e.g. mobility impairments and partial sight which each have their own issues, it is difficult to imagine being overly preoccupied with CLL. Also I want to enjoy my life with the people who matter to me, therefore I also want to celebrate the life that I have.
Thank you, Jammin Me. When I next go to the Eye Clinic I will raise the prospect of CLL treatment and ask what they would do to prevent risk of corneal graft rejection.
I understand your concerns on travel time with venetoclax and Obinutuzumab treatment. The doctors have a much greater control on V&O treatment now in dealing with tumor lysis than first start of trials. The Obinutuzumab is used to reduce the tumor burden and chances of tumor lysis.
I am not in a trial using V&O and am 7 months along in 1-2 years of V&O. I had 3 obinotuzimab infusions once a week to start without a hospital stay. After the first 3 weeks it was changed to infusions of Obinutuzumab once a month. Venetoclax pills by month were started on day 15 after start of venetoclax. None of V&O treatment has required hospital stay. Whether I go 1 or 2 years will depend on blood tests results. I have blood tests with H/O doctor visit before each day I had obinutuzumab infusion. After obinutuzumab infusions were finished, then blood tests every month depending on progress. Blessings
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