Hello all, my husband (35) was diagnosed with CLL in January (3 months ago) and to be honest, everything has progressed quickly since then and we are still struggling to get our heads around numbers/markers/treatments etc. so I'm looking to this experienced hive mind for any thoughts and guidance you might have and I'm very grateful for your time in sharing these.
We are in the UK, this is relevant, as I've asked for several things that I've seen mentioned on here (such as CD38, 13q-, 17p- and IgHV status) and been told that 'we don't routinely complete these tests out with clinical trails' however I had thought some of them were relevant for determining the best treatment options. I've asked for these results specifically and been given these answers.
What we do know so far is that my husband has 11q deletion with 84% ATM loss, no TP53 mutation. His lymphocyte count has tripled in just under 3 months (currently at 58.8) and his platelet count has dropped to below 100, though haemoglobin count remains stable. A CT scan revealed probable bone marrow infiltration (though no biopsy), enlarged spleen and several internal enlarged nodes but none severely pushing on internal organs. I'm grateful to say that in general he is feeling well.
my questions are this, should we be pushing to get tests completed for the other numbers (cd38, 13q-, IgHV, 17p-)? Will they make any difference in determining treatment options? Where should be looking to determine the best treatment options for his situation?
If we're honest, I don't think the doctor has been particularly helpful in answering our questions or explaining his decisions. When we've asked about treatment options we've been told that my husband will likely get ibrutinib and venetoclax but with no explanation as to why this would be the best choice for him. Are there any journal articles comparing treatment outcomes that we could be directed to?
Thank you all in advance for you help answering any of these or sharing your experiences
Written by
Nico6
To view profiles and participate in discussions please or .
Nico6, I'm just a patient treated with a time limited BTKi/BCL2 combo in the US, but my understanding is that I+V generally works well regardless of your markers and I believe it is the NHS approved combo. If you can get the tests done it can sometimes help with the mental stress, but my gut tells me your husband is unmutated- IGHV due to his rapid progression, but again...just my layman's guess.
Ibrutinib stops the cancer cells from dividing by inhibiting the BTK protein allowing them to die their natural slow death and Venetoclax kills the cancer cells by inhibiting the BCL2 protein. So the combo is a good two pronged attack on the CLL.
Thank you so much for your reply. Am i right in thinking that I've read that you can only have V&I once? I think I'm a little concerned that having it as a first line treatment might make second line treatment options more limited, but perhaps that's the wrong way to think anyway. I'm very grateful for your insights and sharing your experiences.
Thank you for your thoughts on IgHV status as well, I think that we suspected as much but we know so little and have such limited experience hearing it from someone else is really helpful.
Nico, The theory is that a BTKi and BCL2 time limited combo can potentially be repeated if you did well on it and got a remission of at least 2 years. My treatment (Pirtobrutinib/Venetoclax) is a newer version of the combo. I'm not sure why I+V wouldn't be in this category, but perhaps there is something here I'm not understanding....like NHS rules.
The beauty of time limited is that in theory it usually isn't long enough to allow for CLL resistant mutations to develop which can happen for all the BTKi drugs like Ibrutinib and even Venetoclax if you take them long term.
If Venetoclax + Obinituzimab is offered as a treatment it is a good one too, but you have to realize that the Obin infusions take many hours at hospital and the Obin does lower your infection fighting abilities for a good period of time (perhaps a year or so). All the treatments negatively impact our immune fighting abilities but Obinituzimab an Anti-CD20 monoclonal antibody attacks all B cells good and bad because they express CD20 leaving you a bit more vulnerable to infection.
A single drug like Ibrutinib, Acalabrutinib or Zanabrutinib could be taken long term, but at your husband's young age it would likely drive a resistance mutation after 6 or more years and I'm guessing the doctor wants to avoid that.
There are a lot of new drugs and combos in development and I'm sure 2nd, 3rd and subsequent lines of treatment will offer more good options for him.
Sorry you are having to deal with this. Has your husband seen a Haematologist, and preferably one with experience of CLL. In the U.K. it’s unusual to do a raft of tests until just before treatment. I would have assumed, bearing in mind your husband’s age V&O - Venetoclax and Obinutuzumab would be the first option, but we are lucky that there are so many new treatment options becoming available.
Have you joined CLL support. They run patient webinars and conferences around the U.K. that are very helpful. Also Norah Grant runs an under 60’s group that is worth joining.
Try not to worry. I was diagnosed in 2007, and still around.
Thank you so much for reply Colette. I think we had expected v&o as the first line treatment but no, he's not under a CLL specialist and that is probably part of my concern in ensuring that he is getting the best/individualised care for him.
I actually spoke to Norah yesterday and have now joined the WhatsApp group, thank you ❤️
I'm glad that you're in good health and grateful to you for sharing your experiences
It is very unusual to be under a CLL specialist in the UK.. Where you are will usually define who you see.. Birmingham London and Southampton however do have specialists.. Ask to see a. different consultant if you don't have faith in this one! I did and got another one in Taunton.. Who was a great deal better.. She explains everything and I get to see all my. Results with a running commentary.. I didn't get the fish test. Til just before I started O+V
Thanks so much for sharing this, we are in Scotland. They are discussing my husband starting treatment tomorrow at a multidisciplinary meeting but still no fish test as yet. I wonder if you're right and that we would be better suited to another consultant. Thanks for your reply
Glad you spoke to Norah and she will be a good source of information on up to date UK treatments, but V&I sounds like a good option, and please don’t start second guessing about the next treatment available just yet, it may never be needed.
As I see you are in Scotland you can ask your GP or current consultant for a second opinion with a CLL specialist.
Thank you so much- I think that we will do that. It has been such a huge help hearing from everyone and benefiting from the wealth of everyone's knowledge. Hoping that you also get to enjoy the beautiful day- it's a rare and much appreciated run of sunny days at the moment 😊
I don’t know the UK system, but in the US system ibrutinib has generally been superseded by acalabrutinib and zanubrutinib. Obinutuzumab is also on the standard of care list. FCR chemotherapy may also be an option though I’m not sure that matches your genetic profile. CLLSociety.org can provide further guidance.
At your husband’s age I’d be inclined towards fixed-duration treatments.
The main thing is to make sure you see a doctor specializing in leukemia and lymphoma, and preferably CLL, even if it’s just for initial treatment consultation. 40% of CLL patients get demonstrably wrong treatment, mostly because non-specialists are not up on latest treatments.
Clinical trials may be an option to consider as well. The UK may not have approved all the options the US has on standard of care currently. Trials can be a way to access newer treatments.
Ibrutinib with Venetoclax is a short duration 15 cycle tablet only doublet treatment that has only been approved in Europe and Australia. It is approved for routine first treatment in UK without restrictions, much of the mainland is dragging it's heels, I suspect experience with FLAIR trial has pushed UK use. It was approved for NHS May 2023 and PBS Sept 2024. The 9 infusions of 8 doses of Obinutuzumab are replaced by 15 cycles of Ibrutinib with 3 cycles before the ramp-up of Venetoclax.
It's in NCCN guidelines but was not approved by US FDA.
It will be supplanted by Acala - Ven (AV) as and when NICE get around to approval of it with (AVO) or without Obinutuzumab. It's in progress but the wheels turn slowly. 21 January 2025 - 18 February 2025 Consultation on suggested remit, draft scope and provisional stakeholder list of consultees and commentators: 6232
A-V if approved by FDA will be the first tablet only doublet for CLL in US.
Acala and Zanu are both approved for continuous therapy for those that have 17p/TP53 aberrations or are unsuitable for FCR (as IgHV is not tested! everyone is until they elect Ven-Ibr or V+O).
Ven + Obinutuzumab has restrictions on use to those with 17p/TP53 aberrations or unsuitable for FCR. It can be given to anyone on application for CDF funding. Like AV/AVO it is nearing a review that should approve it without restriction.
This is hugely helpful, thank you so much. If I'm reading this correctly then V&O is restricted in the UK to those with TP53/17p aberrations so not open to the general CLL population at the moment? Are there any journal outcomes that compare treatment outcomes for those on V&I, V&O and AV (if this is likely to supersede both eventually)? Should we be pushing for an alternate first line treatment? I am not sure if I'm correct here, but is it right that V&I can only be used once while V&O can be used repeatedly? Meaning that if we use V&I now do we limit our second line treatment options (i ask this because at 35 we are hoping that overall survival will be long enough to need several treatments rather than playing all off our cards on the first round so to speak). Thanks for your help and sharing your knowledge
If it's a time limited treatment which is stopped before resistance develops to either of the meds, I don't know why couldn't it be repeated at a later stage. Ask your doc. Sorry about his situation. I was 53 and I thought I was young for this diagnosis. I can't imagine how terrible it is at 35.
Thanks so much for your advice. Yes, it has been a lot to get our heads around in the past 8 weeks, but we are very grateful to this community for sharing their experience and knowledge with us
V+O is available for all NHS patients. The doctors have to make a separate funding application to the CDF for those that are suitable for FCR/BR. I've never heard of it being turned down.
CLL17 trial is hoping to answer questions about first line I mono, V+I and V+O. I don't think there is much to chose between V+I and V+O.
MAJIC is testing AV against V+O.
Neither V+O or V+I are approved for repeated use in UK. This needs to be addressed. V+O maybe by ReVenG trial, results are due 2027. I can't see any trial for V+I repeated use other than a handful retreated on CAPTIVATE FD.
Current 2nd/nth line treatment options are cBTKi after prior V+I or V+O and 2 year Venetoclax + Rituximab.
Taking a NHS short duration (SD) treatment V+I or V+O first gives an additional treatment SD > cBTKi/VenR > VenR/cBTKi. The alternative is cBTKi > VenR. There is no answer as which is right or wrong in sequencing. There is an expectation that cBTKi after a SD treatment will have a shorter duration than first line cBTKi but no one really knows by how much. First treatment to progression on cBTKi is known to reduce the duration of response to subsequent Venetoclax treatment compared to those that halt cBTKi for intolerance. The BRAVE trial is looking to wean patients off cBTKi before intolerance/progression by addition of Venetoclax for a year.
The fact that we are now living so long and have manifold treatment paths available makes follow ups for 15-20 years very costly and difficult.
I'm so grateful to you for sharing your clearly very extensive knowledge of ongoing trails and some of the dates that these answers might be available from- thank you so much. I am a big fan of science and data, so find this kind of information reassuring and calming- it really helps with clearer decision making. Yes, longitudinal follow-up studies are incredibly costly, so this makes sense but it's also really reassuring that overall survival rates are increasing to that length.
This is really useful information and a sign of what may be to come on the NHS in a few years. I will look for a CLL specialist here in the UK, thank you for your advice and I'll ask about clinical trails- thank you so much for sharing your experience and knowledge
I am sorry to hear about your husband’s diagnosis ~ I thought my husband was young at 55 to be told he has CLL ( he’s now almost 68).
You are definitely in the right place for answers… there are are some incredibly kind, supportive and knowledgeable people here. Sharing others’ experiences really is a great help.
You must be feeling all sorts of emotions right now, but it’s good that your husband is feeling well… mine did too, and it was a huge shock.
All I can say, from my point of view (as the other half!) is that there is lots of information out there and you will gradually learn which bits you need for your particular case.
Paul sees a haematologist once every 4 months, has a blood test to check the numbers and that’s the only thing we have to do differently at the moment.
He has had two rounds of treatment : FCR - a type of chemo immunotherapy, which I believe is rarely used these days ( it wasn’t pleasant, in that he was very nauseous for a few days each month, but it certainly did the trick) and then he had, about 5/6 years later ( fine in between) a course of Rituximab and Venetoclax. This was much, much easier… and once it’s done, it’s done.
I sincerely wish you and your husband well. I would agree, that here in the UK they don’t seem to do as many test but, in our experience, they certainly do all the relevant tests before any treatment, so please be reassured.
Having said that, if you’re not happy with the doctor you see, I would suggest changing, because you do need to trust their opinion.
I hope I haven’t gone on too long, but I remember clearly how scared I was in 2013 and wanted to give you a virtual hug. Please remember to look after yourself too,
Thank you so much Fran for your reply and virtual hug, it means a lot ❤️ I'm very grateful to you for taking time to write your reply and share your journey- reading about others who have gone through the experience is a huge help. It's reassuring to hear that others in the UK maybe have less tests too and that it's not just us in that boat. I'm pleased to hear that your husband responded well to both treatments- wishing you both continued good health
Your hubby is quite young to join us and as others have said probably unmutated. Loss of the ATM gene and unmutated usually has short time to treatment and retreatment (I am in the same boat). All the fixed duration immunotherapies have potential to be repeated. However with the latest it takes a while to get clinical trials completed to prove they are effective and so get nhs approval. I am a fan of getting the FISH test done early as a prognostic tool. It can cost a bit and that is one reason why they are done prior to treatment. Also cll can mutate so any early fish test will need to be repeated prior to treatment. Now with the rapid changes you have indicated a bone marrow aspirate may be needed soon to get an idea of how much cll is in the marrow. This is a likely reason for falling platelets , but not the only reason. I suspect falling platelets may be the reason he starts treatment. Keep regular blood tests, at least every 3 months if not sooner. Be aware of changes- fatigue, bruising easily, excessive bleeding from very minor injuries, unexpected nose bleeds, petechiae esp on legs. If these things appear get a blood test done asap and see your dr. These are signs of very low platelets less than 30.
Thank you so much for your advice. I was aware that it might be a short time to retreatment considering what we know so far and I think that's why i have so many questions about what order treatments are 'best in' But your reply really makes a lot of sense that clinical trials and subsequent nhs approval for these takes awhile- hopefully more things will be available when that time comes.
I did ask about a bone marrow aspirate as a CT scan showed likely infiltration, but nothing yet. We will keep an eye on all the things that you've helpfully mentioned.
Thank you for your reply and sharing your similar circumstances, really hope that you're keeping well and am grateful for your time in replying
By not testing IgHV NHS doctors are driving a horse and cart through the NICE approval restrictions! I wasn't tested for IgHV. The iwCLL and BSH guidelines say IgHV should be tested but there is no requirement for this to be tested on the Blueteq form they use to apply for treatment funding.
By not testing IgHV everyone is unsuitable for chemo. BSH guidelines say use of BR should be discontinued and FCR can only be given to IgHV mutated, so if that's unknown no one can be offered chemo.
My FISH test results are similar to your husbands, 95% monoallelic del ATM (actually del(11q)) and no TP53 (actually 17p). Results that are not clinically significant are not reported, Tri 12+ and 13q. They will have tested these but they won't report unless Tri12+ is present or del(13q). For some unknown reason West Midlands lab (and yours) have reported FISH tests as ATM and TP53 instead of the usual for FISH test 11q, 17p etc. I don't know what they would report Tri12+ or del(13q) as.
NGS test was done on Bone Marrow biopsy (BMB). Test panel, ATM, BCL2, BIRC3, BRAF, BTK, KRAS, MYD88, NOTCH1, PLCG2, SAMHD1, SF3B1, TP53 and XPO1. 20% of my cells are SF3B1 mutated.
Cytometry results appear on various biopsy results.
My BMB results, I have no idea why the first reports CD79a and second CD79b. CD79a/CD79b are supposed to be a di-sulphide linked pair.
This is really helpful, thank you so much for sharing your situation. It makes more sense why there is less testing of IgHV now and thank you for explaining that CD38 is much less tested in UK. They specifically said that didn't test for Tri12 and del13q but actually your explanation makes more sense that these things have been given different names and are harder to interpret. Thanks so much for sharing your diagnosis and helping to explain things much more clearly than our consultant!
Hi Nico6, Sorry to hear of your husbands diagnosis, I can't offer much as far as medical advice goes, I'm not a Dr and have over the years usually been fine with and followed my Dr's advice. I remember well arriving home to tell my wife I had just been told of the CLL, we were 40 with 3 young sons. That was 1992, we now have 3 grown sons, 7 grandkids and almost 33 years since that 1992 diagnosis. It has not always been easy, treatment 3 times and a few medical procedures. Last treatment was O&V Setp 22-Aug 23 and currently doing just fine. I truely wish your husband the good fortune and success with his health that I have had.
Thank you so much for sharing your story, it really fills me with hope. We also have 2 young children (3&5) and at points over the past few weeks things have felt a lot less positive with regards to the future. Hearing your story is really lovely and helps to remind us that there's so much more still to come- thank you
Hi Nico6, Sorry to read of your (husband's) joining of our club, however, I hope he finds it the forum useful and he has a long future. You can read my bio to see detail of my journey, but at 56 I felt ever so slightly doomed. That was 2012 and time has gone on. I've been through three treatments (FCR, V+I and CAR-T). The latter two on trials. I'm 11q Del and IGHV unmutated, which is not ideal, however, that is a view based on chemo.
There has been a lot of discussion so I will not repeat it. However, in general, your support team should be able to deliver a long future for you. I'm not medically trained so will not make any recommendations other than to suggest you consider the following:
Ask for a second opinion. I did and glad I did. I'm looked after at The Christie in Manchester (I saw London and Southampton mentioned). If you went for a second opinion you may not have to go that far. I believe it is your right to ask for that.
Also if practical consider trying to attend a CLL Support meeting sometime, to network with other CLL patients. It is run by patients (and supporters) and can be found at cllsupport.org.uk/
Try to keep to trusted sources for information. 'Dr Google' is full of old data and strange opinions. I've been on this forum since 2012 and can say that it has proven very valuable over the years because what you read is personal experience.
Finally, never be afraid of asking questions. I wish you both all the very best and good science.
Thank you so much for sharing your journey so far, it really helps hearing other people's experiences. That's interesting about clinical trials and something that we should probably be asking about. Thank you for your advice to ask for a second opinion, we will do that. I will look in to the best place to go for one. I'm glad that you're being looked after by Christie's and am wishing you many more well and happy years ahead.
hi, I’m in the uk. Like your husband I was quite young when diagnosed. That was 17 years ago.
Until you need treatment you may not get those tests but you can ask. Where are you in the country as there are specialists you probably want to connect with ideally. There are so many good drugs available these days so although it’s easy to say don’t worry, you can expect to have decades together all being well.
Thanks you so much for sharing your experience and I'm really hoping that you're right and your confidence and response is really reassuring. Hoping that you also keep well.
You’re welcome. You can see all the treatments I’ve had in my bio. Your husband won’t get FCR as the new drugs are so much better with even newer ones being developed as I write! Take heart and use this diagnosis, one you cannot change, as a blessing that enriched your lives together.
Content on HealthUnlocked does not replace the relationship between you and doctors or other healthcare professionals nor the advice you receive from them.
Never delay seeking advice or dialling emergency services because of something that you have read on HealthUnlocked.
Boost neutrophills/platelets
Seeking CLL specialist in SE UK for pre treatment consultation
Stage 1/2 CLL and no follow-up visits?
Platelets are too low
update: Zanabrutinib vs Obenven (O&V)
