1) there is no hard data, zanu is too new. It didn't get FDA approval to treat CLL until this past January. There is data out showing it is *effective* in del17p patients. Which is where the TP53 gene resides. It's a small study, a little over 100 patients. So it's clinically significant to say "this seems to work in the hard to treat del17p patients" but it's not even designed to say it's better than V&O. Even if you wanted to compare 5 year PFS rates....zanu hasn't been around 5 years yet! Outside of study data. There simply aren't the numbers of zanu patients to even do a retrospective literature search and compare PFS rates. I am unaware if there is even a study out, looking at whether it is superior to V&O. With the V&I fixed duration treatment results, it seems a lot of interest is looking at doublet fixed duration combos in addition to the new agents being developed. There are a few triplet therapy trials too.
I am seeing studies of zanu *with* venetoclax as a doublet, but not once against the other.
If you have a TP53 mutation without a 17p deletion, do you know which muatation it is? There is a database classifying the various TP53 mutations, and whether or not they are associated with various cancers. Some seem to be "more deleterious" than others. It's unusual to have a TP53 mutation without a del17p.
People with bulky nodal disease are thought to do well on BTK's in addition to V&O. There seems to be a consensus that BTK's clear out nodes better, V&O gets deep into the marrow better. So depending on how a patient presents (bulky nodes, little marrow involvement but cell lines decreasing or other organs affected) one may be recommended over another. Since there is no infusion/possibility of infusion reactions, and that it's an oral med that doesn't affect antibody production as long as obinituzumab, some specialists prefer BTK's in bulky node patients. There's yet to be a consensus as to which BTK is "the best".
It's similar to "which is The Best antihypertensive". The answer is, it's very patient specific. Protocols are developed as recommendations where to start, and when to change. There is years of data involving thousands of patients, for antihypertensive drugs.
We don't have the number of patients, or years experience with the targeted agents, to make definitive statements yet about CLL and which BTK is "the best". It may turn out to be like cephalosporins: depending on what you have, one is better than another.
2) yes. PFS starts getting counted when any treatment starts. The Lancet thinks the term is confusing, and proposes a change in the nomenclature:
3) with the new data that came out recently at ASH, a one year doublet seemed comparable to the doublet with 2 years of V. MRD testing is recommended after year one, and depending on the results, V may be discontinued. But you ideally need an MRD test. The idea is to not continue to expose a patient, and their varient, to drug longer than needed. Depending on the specific patient, and how their variant acts, a doctor may decide a longer treatment is needed. I am unaware of any hard data stating exactly what is best.
I'd like to comment on your doc's resistance to using MRD tests. As of the 2020 US recommendations, MRD testing was considered an important assessment tool. Zanibrutinib had yet to come to market, and does not appear in these treatment recommendations of the American Journal of Hematology:
Medicare in the US not only pays for the minimum definitive blood MRD testing, they also pay for the newer more sensitive NGS tests in at least some patients. You know the government here doesn't generally pay unless something has become a practice standard.
Your doc must be reading the literature, since they are on the zanubrutinib bandwagon, yet are ignoring/against the MRD diagnostic/assessment tools. I am baffled.
Have you gotten to see a true CLL Specialist yet/gotten a second opinion from the CLL Society? Just because a particular hem-onc sees the few CLL patients in the area, does not make them a "CLL Specialist". These people attend the meetings, participate in at least panel discussions at medical conferences if not doing actual research studies. There are some great hem-oncs treating CLL patients, but I have never heard of them rejecting a tool the specialists are using. Or making statements that "this is definately better than that" as a generalization.
Thx for all your research and expertise. You are brilliant.
I have No TP53 mutation and no p17 deletion.
My LVHG is mutated well beyond 2%
No trisomy etc.
My blood pressure issue is that it has always run low
I had been excited about fixed duration Tx but after 3 years of COVID, the last thing I wanted was another CD 20 inhibitor ( had rituxan then no antibody response to 6 COVID vaccines and I felt like my doc twisted my arm to go with the V + O). And the grade 3-4 neutropenia was so much higher with V + O that I changed my mind and wanted a BTKi.
But I was so desperate to start treatment as my spleen had been painfully enlarged and my energy gone for 5-6 months, just generally ill like pre FCR.
So instead of holding out for a BTKi, or finding a new doc I just started V + O.
The challenge is my CLL specialist is so heavily involved in research, publishing and presenting (4 days per week in research and frequent weeks away presenting) I've only seen her twice in over a year. It's always a PA or NP.
Even today, 2 months into V + O and wanting to change treatment due current side effects, the nurse called to change my doc appointment on zMonday to see the PA. I explained my teeth have deteriorated rapidly and I'm being told I need screw in dentures which requires 30 extractions and such and really wanted to talk to the actual doc about how to manage bleeding and infection risks. I was told I could discuss it in July with the doc. But based on the progression of decay to abscess having repeatedly occurred in the past, I hope the decayed teeth and erosions don't get infected before July.
In fact, after being told by the doc 9 months ago to start treatment, all my subsequent visits were with NP who kept contradicting the doc saying I did not need treatment. The only way I got in to see the doc in Feb instead of this May is Dr K from CLL society called in a favor.
The decision to treat after the Feb lab work up was called to me by the prior Auth nurse to tell me to start V + O in 4 days without even seeing my doc to review labs, then have a risk/benefit discussion of options. I finally prevailed and got an apt with the doc but she popped in for just a few minutes after seeing the fellow and said I'd do great with V + O and would be feeling a lot better by weekend after starting treatment on Tuesday.
I see now, you rarely get to see the actual *doctor*. So sorry to hear this. Re: your "excessive side effects", I think you are barely out of induction, and that a number of your SE's are due to continuing hard physical exercise in the early part. You preferentially gave your skeletal muscle a large amount of your energy. Not surprising you had more effects than the "average" person who doesn't exert themselves as much. The people here who write "I drove myself home, did some work after my obin infusion" were not out running around doing hard physical labor.
So. If you have major tooth surgery, you can't go gallivanting around, and probably need to rest a bit more, to allow the sutures to heal. Head stitches which include the mouth, can bleed a lot, as you know. So considering you love to exercise but are looking at some upcoming major (30 extractions is quite a lot) surgery, with "non sterile" incisions because of the mouth teeming with bacteria, you've got a conundrum! Have you tried stretching type exercises, yoga, and doing aerobic exercise at a rate where you "meet" the heart rate increase to get into cardiac toning, without doing extra? I wonder if you try that a bit, if your side effects tamp down somewhat.
Then you will have fewer worries about mouth sutures leaking from you exercising "too hard. ". If your platelets are stable, as well as neutrophils, you should come out the other side successfully. A water pick can be used to help gently clean the suture areas, your oral surgeon will likely recommend it as long as you don't overdo it. With decaying teeth and a series of abcesses, if your oral surgeon thinks you are at high risk for infection, it may not be great to wait much longer. Get your various immune globulins checked, get G-CSF if you need it, consider keeping some of that Surgicel powder in the syringe around, and use it judiciously if your mouth is oozing. I know that's "off label", but, better than trying to constantly check platelets and trying to get a platelet infusion if yours is temporarily "too low" or sutures ooze too much. You would have to be very careful to only use a small amount, since it can cause unwanted swelling near bone. One of the facilities I once worked at had a great Wound Care Center, I saw how the docs would get creative with wounds that presented challenges.
I've actually cut way back on activity intensity. Bummer for my mental health but there is good wisdom in it.
I learned my lesson on working out after excision of tumor during FCR. I was at church and my huge dressing and face became blood soaked and it took hours to stop the bleeding
My biggest concern for the teeth is infection and I would actually stop physical activity for bleeding purposes
I had 5 teeth that had root canals. The fillings had been replaced at least twice as there wasn't enough tooth left to retain a filling. One by one they had fallen out yet again. The Macmillan guide to my cancer told me it needed sorting. It resulted in a one month delay to starting V+O, NHS waiting lists for dental surgery got queue jumped.
If this was engineering they would have a spreadsheet and check list of things to check in the workup. Not leave it to the patient that hasn't any idea of what to ask about.
Long story short, I thought after $12k of dental work that I was all set to start V + O but things rapidly deteriorated to having about 8 normal teeth, 3 extracted teeth, and there rest with erosions down to bare bone on 14 and cavities around the previously treated teeth. all in the past few months.
Details
I'm a surgeon and I have a check list with all these sorts of things to prepare patients for surgery. I haven't been given one for this treatment, but my medical training helped me make my own.
I've not heard of the Macmillan guide. How can I get a copy?
I spent 6 months pre FCR having fillings, fillings under crowns, replaced crowns, redos of infected root canals so it was all done pre treatment.
I started in May 2022 to get it all squared away pretreatment. Once I learned of all the same issues in a bunch of teeth, I reached a decision that I wanted to have all the bad teeth pulled and get removable partial dentures so I could remove them and clean. My dentist wasn't going for it. In a meeting with him, the denture guy who is a friend of mine, the dental tech took over and told us all that we needed to do a bunch of crowns, bridges etc. As treatment was coming up soon, I opted to have 3 teeth removed and all the other things done. Then a few months later, a week before starting V +O I went in for a check up and had a painful tooth treated.
Since then the lower front 8 teeth started impinging on the backs of the uppers. It started with one and progressed rapidly until all the enamel is gone, and there are multiple new cavities around old crowns and root canals.
I've seen a new dentist about a partial denture and build ups, but things were a lot worse than I had anticipated. She is reviewing all the images and impressions she took with partners to devise a plan.
So when I saw my friend, an oral surgeon for what I originally thought would be considering 3 implants and some build ups, I have received the new news of all the other things, he recommended full upper and lower "same-day" dentures stabilized by 10-12 screws into bone.
Monday I meet with the oncologist to sort this all out. What is more risky for the procedures or leaving things alone for the next 2 years and dealing with each tooth infection as they inevitably will continue to develop.
I think it's more for patients benefit, making it easier to understand. As people are trying to learn more abouth health conditions, and with the Internet allowing easier information access than, say, 20-30 years ago, it's not particularly intuitive IMO. It's not intuitive that a 1 year treatment with a 5 year PFS rate has a longer time "off the drugs" than a 2 year treatment with a 5 year PFS. Both treatments have the same PFS, and PFS is how treatment regimens tend to be discussed. If one is comparing "PFS rates" of the 2 treatments and they are the same, the effect on a patients lifestyle is not quite the same.
And now that the BTK's are around, and people are on them indefinately, how do we differentiate between patient groups that are on meds indefinately, symptom free, and others? If the PFS is the same for 2 treatments, but one is 1 year and the other is 3 years, how to make sure a patient understands the distinction? How to we use a terminology that adequately describes the process and outcomes for a patient, when the treatment lengths vary uo to "indefinite" as well as when trying to describe the differences pro and con when developing treatment algorithms?
It's exciting we are reaching a point where we *can* have treatment algorithms! Instead of only 3-4 things that one tries sequentially, ending up with a BMT/SCT. So it seems rational to question the terms we have used previously, and discuss alternatives. Especially with the newer markers and their prognostic significance being questioned, plus information on the "older" ones. Like, I was given a horrible prognosis based on the del17p plus TP53 plus enough other changes to be "complex karyotype"....but I think my IGHV being "mutated" wasn't appreciated or considered strongly in my initial diagnosis. Who knows yet, if this is the reason I am responding to treatment, let alone if my particular type of mutation appears to be "more favorable". Similar to how a few of the reported TP53 mutations do not seem to have strong negative health consequences.
Oops, I made a statement that's confusing/erroneous. It was a poor word choice/sentence structure to say "it's unusual to not have both TP53 mutation and del17p". Although they usually *do* go together, the incidence of them *not being together* isn't rare. My using "unusual" makes it seem like it's on the rare side when it isn't. Thanks gardening-girl for catching this! I probably meant to write "it's not usual to have TP53 mutation without a del 17p" but typed "unusual" which is more than my usual simple typo. Do 't ask me why I wrote such a convoluted sentence, IDK
I'd suggest a dental plate or partial dentures that are moulded to the gums and don't need screws. Then get the full works when you are out of risk of infections, bleeding gums etc.
The booklets may be a bit basic for medical professionals.
CLL recently updated, major change is MABs have been moved before chemo.
Anyone diagnosed with cancer in UK gets a 3 inch thick stack of these booklets. Every hospital with a cancer unit has a Macmillan support office with all the literature on racks outside.
This will upset you. Each band covers the whole treatment sessions with multiple visits. 5 root canals all in one fee. Top and bottom dentures all in the one fee.
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.
3rd Covid shot while still receiving (O & V)?
V+O treatment 
