I was diagnosed with stage IV accelerated SLL in January 2021 and started treatment with BTK inhibitors in March 2021, so 16 months on BTK inhibitors so far.
I went off acalabrutinib nine days ago in preparation for a surgery - I was told to hold the medication for seven days before and after.
Already the lymph nodes in my neck have started to swell. They hurt and I can feel them with my fingers, about the size of kidney beans.
Has anyone else experienced such fast recurrence when off treatment? I'd have thought (or hoped) it would take longer for the disease to flare up when off treatment but apparently not.
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Amberesque
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Yes, I will definitely tell my docs about this. The pathology from my diagnosis states I have an aggressive "accelerated" form of the illness but when I ask my doctors about that, they don't know how to interpret it.
When I was preparing to go off acalabrutinib for surgery and was concerned about disease flare, my doctor said she wouldn't be worried if I went off it for SIX MONTHS!
That is in direct contrast to the studies I've read which state it's important to have a back-up plan in place in case BTKs fail because disease resurgence can be fast and hard and survival short.
The story of my diagnosis and treatment has unfortunately also been one of trying to get doctors to believe me and read the latest research because they don't seem to be up to speed where I live. =(
I know, I have an aggressive variant too, and most docs are unfamiliar. I mean, people here are reporting *organ infiltration* which is rare in the literature. Unless one is going to a doc that publishes/sends case studies or Letters to the Editor to medical journals, the percentage of this is likely under reported. They may read up/research it, but may not be well versed in the "possibilities" unless a specialist, and an experienced one to boot. I just carry copies of research things (my iPad has it's own data line if no WiFi available) and I show them the study/article online if I haven't printed it out for them. But since we *do* have a rare cancer, I am prepared to be my own advocate. If I had a more common, mainstream disease the docs generally not knowing would upset me. But ours is rare, so it is what it is. Glad I found this place once I started having problems. Please don't be distressed your docs don't seem highly experienced, this is relatively new territory for us all. Just put your own "backup plans" in place if you can. Continue to educate yourself as best as possible, and plan accordingly.
My perspective is, 20-30 years (perhaps even 10) ago those of us with these aggressive/unusual variants, would have died fairly quickly, so no opportunity for anyone to study/assess. The newer agents are keeping us alive now, and so *we* are the generation of guinea pigs that future docs and patients will draw on for statistics, likelihoods, side effects, etc.
I agree, I have what I refer to as aggressive CLL. Went from 11K WBC to 197k in 14 months. I am now starting to relapses after almost 4 years of remission, but ALC is doubling every 3 months, so still as aggressive as ever. Whole bunch of new CLL meds out there. Blessings.
Some of us have even gone through the worry of thinking we have developed Richter's Syndrome/Transformation, with a few even being treated for this frightening, fast growing, but curable lymphoma, which we didn't have. Your CLL tumour flare should be reversed when you go back on acalabrutinib.
Please keep us informed of how you go. I hope you are able to go back on acalabrutinib very soon.
Do you know your prognostic markers? I would expect that tumour flare is more likely with poorer markers.
I will definitely keep you posted. I have 5 more days before I can go back on the acalabrutinib.
As to prognostic markers, the only one I have is unmutated IGHV, none of the others. But the pathology did show aggressive disease due to dense proliferation sites.
I have the SLL variant so we have to monitor how I'm doing through assessment of b symptoms rather than blood tests.
As to this acellerated form of illness, I have read that it is indeed frequently mistaken for Richter's.
Considering you are having a flare, I wonder if your surgeon will OK an earlier restart. If any stitches are external, they can be assessed and you possibly restarted sooner, if the area has healed faster than anticipated. It would be prudent to allow "extra time" for stitches if possible (since we may not clot/repair like normal people), but it sounds like this might not be an option if your airway starts to get compressed.
After 2 years on Ibrutinib I went off it for a few days to see if my fatigue would improve. My doctor suggested this time off and said I could probably go off of it for months before seeing any changes. Within 3 days the lymph nodes in my neck swelled up. Luckily once I started Ibrutinib again everything went back to normal within a couple of days.
Yes, this happened to me with just three days off Acalabrutinib before a colonoscopy. The lumps in my neck surged back and were painful too, which they had never been before. They went away again within a few days of starting back on the Acalabrutinib. I was concerned about all the good work being undone as I was starting Obinutuzumab a week later. My bloods were still great, thankfully, and seemingly unaffected. However, it was only three days. I am due to come off again next month for a BCC removal but will argue against the 7 days the hospital wants. It’s too depressing and scary the speed my lumps came back. Hopefully you will be fine once you are back on the Acala.
You may have had enough treatment that any flare will be less pronounced, if it happens at all. And I will mention, any external stitches may take longer to heal. So please consider assessing any stitches/how you feel, before deciding ahead of time you want to go back on faster than recommended. Discuss it as an option, but perhaps wait to see if it's needed.
I had one biopsy where I went to a new derm to have stitches removed; they didn't look healed to me (I have had stitches before) and the derm didn't even assess me, just sent in a nurse/PA to take them out without inspection to see if they had healed. It happened so quickly, I couldn't stop them; I wanted to ask "I don't think this has healed, should it wait" but this person just walked in, looked at my leg, then *snip*. They were carrying a small scissors which they didn't clean before snipping. Needless to say, the wound popped open, and "they couldn't do anything". I now have an unnecessary scar. And I refused to pay their copay for the office visit, too!
When I was on ibrutinib for 5,5 years my nodes would enlarge rapidly every time I had to stop. It is frightening. They always regressed when I restarted the drug. Good luck. Tony
I’ve been off my acalabrutinib for two months as I was unlucky enough to be diagnosed with endometrial cancer in November for which I had surgery followed by radiotherapy and chemotherapy - I was taking acalabrutinib alongside until the last 2 doses of chemotherapy when I was neutrophenic and my CLL consultant advised me to stop taking it until treatment was over. I am restarting it next week but I haven’t had any swollen lymph’s and my blood results other than white cells and neutrophils have stayed normal, but I understand a “flare up” is common from posts I have read from this community so hoping you see good results when restarting!
I have tried going off Acalabrutinib unsuccessfully three times. Each time I became quite ill within days and my lymph and spleen got huge. First time my WBC went from 18 to 130 in 3 days and I was diagnosed with a transformation to acute lymphoma. Fortunately I did some research and found another doctor to help sort out what was going on. Interestingly, we did a FISH during the flare and my 11q deletion was no longer showing up. We had a theory that an aggressive BTK addicted clone develops during prolonged BTK therapy and the different cytogenetic profile tends to support this. This can’t be good so the question now is what to do about it. I started Venetoclax and Rituximab hoping we could knock out the clone but so far unsuccessful. I tried going off the BTK twice while on the triple combo unsuccessfully. I’m really regretting starting BTK therapy as my first treatment as the impact of this clone/transformation to a highly aggressive CLL variant is so poorly understood and appreciated.
Thanks for sharing your experience. I have unmutated CLL and doctors wanted to do chemo but I talked them into BTK inhibitors instead. I've been on them for 17 months now. Frightening prospects. 😔 I hope you get some successful treatment.
I am not sure what you mean by a "BTK addicted clone?" The theory behind cancer resistance is that after drug exposure, cells start dying. The most sensitive ones are killed first. Some cells may not be as sensitive, and aren't seen until the sensitive ones are killed off. Also, evolutionary pressure for survival on the cancer leads formerly sensitive cells to mutate so the drugs aren't as effective. So I don't know where the "addiction" comes in.
flipperj , as SofiaDeo explained, treatment drugs select for clones that aren't susceptible to the drug. So if an aggressive clone arose that also had BTK resistance, it would quickly become the dominant clone as clones susceptible to the drug were killed off, such as your 11q del one - a good one to lose! Different sub-clones arise over time, particularly during treatment and more so with the older chemo treatments (BR, FCR etc), which you were able to avoid.
Addicted is the term my doctor used loosely to describe the behavior of this clone in relation to BTK. This situation is different than that of the classical pattern of drug resistance. Here we (theoretically) have a clone that develops in parallel to the treatment with the BTK inhibitors. It is BTK sensitive but has acquired extraordinary virulence. When we remove the BTK inhibition, the clone rapidly dominates with a replication rate that is not typical of CLL. In my situation, what I experienced progressed more rapidly than a Richters transformation according to my doctors. It’s a bit troubling that this class of drugs can induce such a change in the disease and so little is known about the prognosis for those of us affected. The progression I experienced over months and years prior to therapy now can happen in a matter of hours or days.
Wow, I am sorry to hear this. Clonal dynamics like this are probably behind the protocols using 2,3 or more agents as opposed to single agents IMO. The various clones need to be tamped down all at the same time.
That’s why I went with a triple drug regime when I realized what happened. Still, I think the industry should reconsider using BTK inhibitors as front line therapy or at least include a black box on the risk.
11Q and Unmutated. I had a comprehensive genetic testing done at diagnosis which included BRAF etc., but didn’t have it repeated as it was quite expensive.
is the comprehensive genetic testing at diagnosis you mentioned here named “GENOMIC SEQ ANALYS DNA&RNA ANALYS 51/MORE GENES” 81455 (CPT®) by any chance ?
I had a blood sample sent to FoundationOne Heme. It's a sequencing for hematologic malignancies which covers about 400 cancer related genes. I can't say I derived any specific benefit from the test as the significance with regard to the path of treatment for CLL is unknown for the majority of the genes. It was $3,500 out of pocket, and in hindsight, probably not worth the expense.
my husbands CLL specialist Dr Siddiqi at City of Hope was mentioning something like that, paraphrased “we use and are only dealing with clinical tests and treatments, not experimental / still in research” tests (I was asking her about the Ighv3-21 R110 test )
I take it that you took the comprehensive genetic testing you are referring to at own initiative , bypassing the bureaucratic paths of insurance/medical groups?
My CLL specialist at the time suggested the test as the most comprehensive genetic sequencing available. I had my local oncologist take the sample and send it in. Insurance didn't cover costs but I knew that was a likely scenario going in. The test itself is fully validated, so it's not experimental. It's the application of the results to real world situations that is not fully understood and/or endorsed beyond the obvious things like 11Q, ATM deletions etc. These can be tested with a small panel much more cheaply and the clinical significance is established so it's more likely insurance picks it up.
over the following months we will learn more about all the genetic testings available currently . I myself am referred to genetic counseling (I am non CLL but with a lot of cancer cases in family - so I get myself testes to rule out the well established oncogenes I assume, and indeed I may decide to get more tests available done out of pocket - we’ll see - appointment scheduled mid Dec)
and as for my husband who is the one with CLL: we have just entered the CLL specialist era (we are very pleased with Dr Tanya Siddiqi and the new City of Hope establishment in Irvine ) and our HMO plan approved all the testings ordered performed at the lab in City of Hope, done yesterday (including the GENOMIC SEQ ANALYS DNA&RNA ANALYS 51/MORE GENES” 81455 (CPT®)
the genomic test takes a month for results to come back .
I hope all works out and he continuous to receive good care. My local doctor didn't know what to make of the sequencing results and by the time I received the report, I had moved on to another specialist who had little to say about it.
hope you are happy or satisfied with your current specialist and that your CLL is or will be under control soon. I do recall your CLL case being rather very unpredictable . Is your CLL categorized as a stereo type subset by any chance? (Ighv gene)
Thanks. I'm unmutated which is typical of 11Q. I suspect my CLL population is more heterogeneous than some . It's the altered growth kinetics that I have acquired as a result of exposure to BTK inhibitors that is my main issue. It's like I'm dealing with a completely different disease now.
yes, that’s what I do recall from earlier posts of yours wherein you explained that and it is upsetting that the BTK inhibitors tend to do more harm than good in your case (your CLL clones actually loving and consuming the BTK inhibitors to its own advantages ..bastards! )
Your current treatments, a mixture of all sorts, I believe, do kick in? Any improvement in your blood numbers and over all health?
A year of triple therapy has my ALC down to normal but still some lymph nodes so I doubt I’m looking at uMRD. The plan is to try going off treatments in Feb and see what happens.
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Alterations of the immune system caused by CLL B‐cells 
