Questioning if I should question my doctor's d... - CLL Support

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Questioning if I should question my doctor's decision to start treatment or decision not to order genetic testing before that Tx.

gemit2000
gemit2000

[ Dx 2013, 13q, mutated, basically asymptomatic]

Sept lab results were personal worsts (both red & white enough to make one blue). ALC near 100K, RBC, Hgb, & Plt all abnormal for 1st time. But it was the anemic hemoglobin # (by which I mean the # indicated I was anemic), that seemed to trigger the decision to treat ( 2 yr fixed duration VenG); HGb had gone from 13.2 in June to 10.0. They say a drop of .8 is cause for alarm so this being 4x that seems more like it was a 4 alarm fire (or an alarming lab error).

Yesterday I took tests prior to Tx - Haptoglobin, Coombs, & Hep B came back normal & could say the CBC was normal too or back to my old abnormal normal resembling results from all the other tests in the last year or two. My Hgb is back to 13.8, right where it was hovering since 2016. The one outlier now is the one being used as the basis to start Tx.

I'd been fully accepting of the decision to start Tx, especially liking this powerful V+G combo that might free me from the land of the immunocompromised (& from that 'kinky" feeling of being 'so tired, tired of waiting, tired of waiting'). And Tx would fit quite nicely into my new empty life of Covid. In the past I surely would have resisted the decision to treat based on 1 test (happened in 2014 when told I should start Tx due to my ANC going from 4.0 to 1.0; never saw that doctor nor a an ANC of 1, 2 or 3 again). But now I'm kind of feeling if the doctor reverses his Tx decision, I might resist that!

-----------------------------

Whether to treat is my new day old question. My original (week old) issue I planned to ask here was if I should insist on genetic testing. I explained to his office what I knew about the importance of at least a 2nd FISH, but they said the doctor said I didn't need them. I linked them to the CLL Experts on CLLSociety.org's "Test Before Treat" page - cllsociety.org/2019/11/expert-cll-doctors-speak-out-on-test-before-treat/ - where elite CLL doctors gave testimonials in universal agreement that everyone starting a course of Tx for CLL does need them.

However I did note these recordings were made at the Dec '18 ASH and wonder if they are still appropriate. Seems to me the tests main purpose is warn patients off chemotherapy if tests show new abnormalities. But what if chemo was not going to be a Tx option. It wouldn't be for me. So if I'm to be treated, whether now or later, is my doctor correct that since I'm headed for VenG, genetic testing would be unnecessary?

Thanks, Gene

61 Replies
oldestnewest

I had the same questions with similar markers earlier this year.

If you end up with del17p or a TP53 mutation, they might want to recommend a clinical trial or continuous (not fixed duration) treatment.

I ended up getting the tests before treatment and they found del11q in addition to my original dx markers. I opted for acalabrutinib and it's been great.

gemit2000
gemit2000 in reply to avzuclav

good advice. A few days ago I entered my data into this tool (link from CLLSociety.org - clinicaloptions.com/oncolog...

It's where 5 experts give their best treatment option based on that information. I did it for 2 scenarios concerning whether I had developed 17p del,and/or p53 mutation or not (don't think they had 11q del as an option. For both scenarios the majority #1 option was exactly the VenG my doctor plans. There were references to acalabrutinib and 1 or 2 others but I left that site quite ok with the planned Tx plan.

I'm going to ask my doctor at next week's visit if having any other markers like 11q would change his mind as to medication or treatment duration (of course this is if he doesn't tell me he changed his mind about treatment altogether)

Thanks

avzuclav
avzuclav in reply to gemit2000

Not much nuance in that treatment calculator. More FCR than I expected!

I was all set for V+O but changed my mind at the last minute. It will be a long time before we know the best choices, since all these new treatments works so well.

For V+O, I find the supplementary appendix from the CLL14 NEJM paper to be most interesting, I especially like looking a subgroup analysis (page 34).

nejm.org/doi/suppl/10.1056/...

gemit2000
gemit2000 in reply to avzuclav

the tool did get in my heart issues as well as mutation status, and 17del / p53 status, but true, it was pretty skimpy on asking for data, not factoring in countless other genetic variations and other health issues. Maybe I liked it because of some selection bias, since since ever since I read about the first results coming out on V+O trials, I remember thinking that's what I'd want to blow this thing out of the water.

But I've always fought those who decided I should be getting chemo even when I was in the younger healthier cohort with favorable markers. Then finally when new novel orals were approved for the frontline, I knew I could avoid chemo and avoid the small but scary risks inherent with that therapy.

I did go to the Supplemental Index of the trial and bookmarked it so thanks.

Hey, one of the results on that treatment tool had something I didn't quite get and maybe you would understand it better than I do:

"Would recommend if patient desires time-limited therapy which may initially be more labor-intensive vs acalabrutinib. Otherwise, would recommend acalabrutinib. "

Are you be able to translate?

Be well, Take Care

avzuclav
avzuclav in reply to gemit2000

Sure, maybe they meant acalabrutinib is easy (pop a pill at home) vs "labor-intensive" (sit in cancer center for infusions for O and monitor labs closely for TLS with V). If you want approved time-limited therapy, then choose V+O. Someday we'll likely have the option for time-limited pill-popping (when I+V or A+V are approved).

I chose acalabrutinib partly due to the great results in first-line treatment in the OSU trial... "At median follow-up of 53 months (range, 1–59), 85 (86%) patients remain on treatment; " (EHA 2020) library.ehaweb.org/eha/2020...

I changed my mind from V+O after seeing this slide at ASH 2019 (but really either option is excellent compared to when we were diagnosed).

healthunlocked.com/cllsuppo...

gemit2000
gemit2000 in reply to avzuclav

a bit brain dead right now but I picked up most of you thorough savvy response.

Can I ask though,

1) do you know if any study did the V+O for 2 years cause that's my doc's plan. His interpretation might have been the same as yours

2) was the study for frontline, R/R or both?

3) did they break out results from different cohorts like mine mutated + 13 q del

4) and with acalabrutinib, any studies like done with ibrutinib showing it to be problematic for CHD comorbidity (had a bypass 2 years ago and actually after that I almost forgot I had CLL and almost stopped visiting this website; I should chart my website visits since 2013 and it would look like the first year of V+O on your chart, but the slope would keep going down till it was virtually undetectable, a uMRD 5.9).

Thanks for taking the time with me. You seem to know your stuff, more than I know and more than what I know plus what I forgot. Appreciated.

avzuclav
avzuclav in reply to gemit2000

1) I'm not aware of an V+O for 2 years, but if you search up "MURANO CLL" you'll see it was a similar study of V+R for 2 years (and it destroyed BR).

2) The CLL14 (V+O) study was frontline patients with "coexisting conditions."

3) The CLL14 (V+O) subgroup analysis is what I sent earlier. For acalabrutinib, there is a subgroup analysis here (same comparator as CLL14, Clb+O). (Best subgroup was <65yo)

calquencehcp.com/cll/effica...

4) I have no idea. Perhaps you can consult a cardiac oncologist? This could be why your doctor is steering clear of any BTK inhibitors.

No worries, this forum is a great place to strategize and debate.

gemit2000
gemit2000 in reply to avzuclav

great info, thanks

MsLockYourPosts
MsLockYourPostsVolunteer in reply to gemit2000

Re: Results on the treatment tool, I read that that acalabrutinib is recommended unless the patient wants a time limited study. Anyone else?

I would definitely want labs done again before making a treatment decision. It sounds very much like lab error on the one test. I don't remember whether your doctor is a specialist. I'm surprised that he is resisting doing a FISH, etc.

Keep us posted.

When I used the tool acalabrutinib was listed by 1 experts, as something to consider if patient wanted a less labor intensive therapy than V+O. Though 4 experts recommended V+O, surprised 1 advised BR while 2 also would consider BR.

I'm in Central Florida and only find a handful of CLL Specialists/Experts from the various lists. I started with a hemotologist/oncologist at MD Anderson Orlando. The facility ended that affiliation and became Orlando Health UF Health Cancer Ctr (ended that affiliation this year and will be called Orlando Health Cancer Ctr in 2021) I'm still there but changed to a doctor whose bio shows a specialty in leukemias. But I'm with you where I can't see the harm in ordering FISH (perhaps minor harm to my bank account). If it detects some new genetic abnormality others seem to feel this could impact the decision to do a 2 yr fixed duration course and might impact the dosages used throughout.

MsLockYourPosts
MsLockYourPostsVolunteer in reply to gemit2000

Your case sounds like a good one for the cllsociety.org on line consult program. In Florida it's really Dr. Pinilla at Moffit or Dr. Chanan Khan at Mayo. They've both been around for a while, so I suspect that they both may have younger associates coming up in the CLL world.

I actually contacted both - Pinilla I saw (loved his nurse practitioner, found him hard to follow) and the plan as I told Chanan Khan was to switch to him at time of Tx. Then because of insurance I switched back to where I started @ Orlando Health(when it was MD Anderson) where I now have the original doctor I wanted at Dx and they wouldn't assign me to (angry emoji). The one I got told me in 2014 because my neutrophils had gone from 4 to 1, I should prepare myself to start FCR. That's why I went to Pinilla. He agreed that the neutropenia was treatable without treating the CLL. At that moment as was done with Orlando Health and the ANC level at 1 was done too, as it's been in the 3 to 4.5 range ever since.

Now 6 years later back at OH with a new doctor (was recommended & had a bio that includes leukemia as specialty) & he seems to be doing the same thing. An Hgb # which was always in the normal range goes from 13.2 to 10.0 and he says time to treat. Experts I've read say first you make sure the number is real by retesting, and if it is you can treat the anemia without treating the CLL.

I was resigned just to stick with him and avoid numerous 3 hour drives to Jacksonville but now I'm not sure. Wonder though, when Orlando Health was called MD Anderson, it wasn't as prestigious as it's name, so is going to the Mayo Clinic in Jacksonville any upgrade due to the name?

Thanks for responding.

Sorry for going on (if you look at this thread you know it's a bad habit of mine)

MsLockYourPosts
MsLockYourPostsVolunteer in reply to gemit2000

I know that there are hospitals that contract with MDA to use the name, but which are not truly a part of their system. I don't know whether they have any true satellite offices.

Mayo has three sites - Rochester MN, Jacksonville, FL, and Phoenix, AZ.

I got the feeling in the 3-4 years @ MDA-Orlando that that name didn't mean much. When they dropped MDA and affiliated with UF Cancer Ctr it seemed they did join together for mutual benefit in some limited ways.

Do you know if satellites like Mayo Clinic, Jacksonville share resources, missions, culture, etc with Minnesota? That would be where I'd go if I decided to work with a CLL Specialist (though I'm thinking insurance coverage or lack thereof could be a factor).

Thanks

I like the idea of getting tested before treating to have a new baseline before you treat. I am in the more information is better than less category. FISH testing is not invasive and not terribly expensive. What’s the harm?

That said, I think your doctor is right that in your case the results of a FISH test would probably not impact your treatment choice. The main reason doctors FISH test before treatment is if chemo is being recommended. Chemo is not appropriate treatment for 17 p Cll and some doctors don’t use chemo for unmutated Cll. You are not having chemo and are mutated, so I see your doctor’s point.

We do not know what the future holds for Cll treatment and if having an historical record of how your FISH changed over time might factor into a future treatment decision. It’s possible your FISH history, while maybe not terribly relevant today for your choice, might be in the future.

I don’t know that argument would be persuasive with your doctor and I don’t find his position unreasonable. But I do see a possible benefit of having a record of your FISH status now for future reference and zero downside, but for the cost of a FISH test (maybe $750, I don’t know).

gemit2000
gemit2000 in reply to cajunjeff

I'm with you all the way. I want all the info available. In the beginning I lobbied for both a ZAP-70 and IgVH and got them done. But in the last couple of days the doctor has now twice replied to my appeals that I do not need FISH and he would not be ordering it? Figure it's not worth any tension my continued request would cause even though I think my insurance would cover it in full.

Now the bigger question is if he's seen yesterday's CBC and realizes what he based his Tx decision on is not relevant in this iteration. And if does change his mind will it change mine which may mind if he no longer thinks Tx is needed.

Thanks for your support and (amazingly) quick response.

gene

AussieNeil
AussieNeilAdministrator in reply to gemit2000

I expect that FISH testing may well prove useful to differentiate which patients do well on limited time non-chemo combination therapy vs long term maintenance monotherapy. Watch for patterns developing in progression free survival in those who have completed non-chemo combination therapy, and indeed variations between the different non-chemo combination therapy options.

Neil

gemit2000
gemit2000 in reply to AussieNeil

not being clear what traits make doctors choose between fixed duration or ongoing therapy, so I wasn't how my doctor even arrived at a 2 year fixed duration (I had read, I think it was on either the V or G website, they had a recommendation for 1 yr. fixed) But the point you bring up I will bring up with the doctor.

Do you know of any specific literature that discusses which method of treatment is better for which combination of markers like Some decision grid?

Thanks as always for your input. I haven't input much over the last few years as my disease seemed to have plateaued for that time plus my focus shifted to the surprise news that though fit, I had my father's bad heart genes and wound up with doctors tooling around my coronary arteries.

Hope you've been well Neil despite this crazy 2020 (and I'm sure you'll agree none have had it crazier than we here in what I'm hoping remains the U.S.... surreal stuff).

Gene M. aka' mutated Gene'

AussieNeil
AussieNeilAdministrator in reply to gemit2000

I haven't seen any firm evidence yet that could be incorporated into a decision flowchart, but it could be that complex karyotype patients are more likely to do better on a maintenance regime. Watch this space :)

gemit2000
gemit2000 in reply to AussieNeil

Thanks. Makes sense.

Somewhat apropos is a HU member I know and from what my I can recall she had the same markers I have,, sought treatment but did have genetic testing prior to it and found she had developed a complex karyotype (if that's the proper way to say that). Went on V monotherapy of unfixed duration around '16 or '17 and her MRD kept inching (maybe more like 'one trillionth of an inching') toward undetectable. She kept on a maintenance schedule until recently but finally just recently reached undetectable status and stopped. Next test will be a biggie. And hopefully she'll be on a regime of 'nothing needed' for a fixed duration of a few decades.

gm

cllady01
cllady01Volunteer

This may be what you have shown your Dr. , if not here is another such declaration in regard to testing at treatment time:

captodayonline.com/ighv-gen...

Have you asked what the Dr. means by "its not needed in your case"? Is it Venetoclax that makes the difference? I ask, because I don't see any mention of Venetoclax in the article above.

Hi Gene, Your September hemoglobin of 10.0 looks like an "outlier" compared to the ones before and after. It may have been a lab error.

The blood tube that they take for haematology testing contains anticoagulant to prevent the blood sample from clotting. When they take the blood, they have to immediately mix the tube properly to dissolve the anticoagulant. If they don't, clots may form in the sample which may not be detected during the blood count testing. When clots form (even small ones) they trap red cells, white cells and platelets in the clot. This lowers all the counts in the rest of the sample and gives you false results. If you phone up the lab on the same day they can check for clots in the sample, but it's too late to check now.

If it was a faulty sample, these results should NOT be used for any decision-making. The high ALC by itself is not enough to trigger treatment. And if the hemoglobin and platelets are normal again, they wouldn't trigger treatment either.

Cheers. - Jim.

gemit2000
gemit2000 in reply to guzzifan

Bingo, now that I got this pre-treatment CBC result. We now have a range of 13.2 to 14.2 over the past 2 years with last week's at 13.8.... if you take out the 10.0 of 3 weeks ago.

Even without having the medical knowledge you do I felt the same way... a 25% drop when it never fell more than 5% over 8 years and it was never in the abnormal range till then, same for RBC, always normal. Platelets had started to dip below 150 so this 122 was striking but not shocking. Went back to 145 on this last go 'round. So yes all the reddish stuff went down based on a blipp'n error. The white, however, also went in the bad direction up, though I think you're saying their mishandling should cause that to go down too. ALC from 86 to 95 (and now back to 85).

Thanks for making sense of it. Why didn't the doctor? I literally have spent about over a score of hours (1 score and 7 years ago at diagnosis, my doctor brought forth.... ) researching, questioning, searching for 2nd opinions, on this site, on that site, leaving messages to his office, watching the all day webinar today on CLLSociety.org. I would have done none of that.

But once I thought about treatment I really think I want it as I've replied to others here who responded. And no matter everything I'm learning now will hold me in good stead for the moment I will start treatment , whether in a couple of weeks or a couple of years or a couple of scores of years (means I'll get Tx @ 106... well my Mom will be 96 next week so who knows).

Thanks for your expertise.

Be well

Hello, I had a somewhat similar occurrence this summer. I am 13 q UM, for 6 years. My ALC has crept up to 100,000 at an “acceptable” rate doubling >2 years. Suddenly in June I developed Macrocytic Hypochromic anemia ( large pale red cells) My Iron saturation was way down. Haptoglobin nl suggesting absorption problem rather than blood loss, hemoccult stool test normal X 3. I was put on 65 mg of elemental iron and anemia resolving with no other intervention other than stop 25 mg supplemental zinc which I had been taking because of covid.

Interestingly, I had been taking 25 mg of zinc daily for 6 months prior to discovering the anemia. For zinc to be absorbed in the small bowel it competes successfully with iron and copper. Iron and copper are necessary for bone marrow to make hemoglobin. My iron and copper stores were woefully low therefore decreased production of pale red blood cells.

Just a thought, if you were not supplementing with zinc my situation will not apply. However, looking at you total iron saturation and copper levels (which is needed for your body to make ceruloplasm) would be reasonable to ask for.

Ron

thanks. but I do happen to be zinc-free (supplementally speaking). However the hemaglobin level of 10, which is the upper borderline # for both anemia and indication and seemed to be the # that triggered my doctor to decide on treating, was very suspicious to me. My RBC did go from normal to abnormal but in a fairly usual amount of 3%. In the past that's how my RBC, Hgb, and Plts would trend downward - nothing dramatic and never even the .7, .8 I read that would gain a doctor's attention. No, it went down 4 times that ,around 25%.

So 3 weeks later what is it? 13.8 and that's the highest it's been in 2020. Also haptoglobin came back normal as well as Coombs the Heps. So there goes his reason to treat.

However, I wouldn't fight him if even based on the stable #s I saw this week he stuck to this decision to Tx, because as I've said elsewhere in this thread, I'm an impatient patient who wants his immunity back. I'm doing without the group activity that provided me with exercise and a social life and now in my home alone about 99% of the time. To me that's indication to Tx before insanity strikes.

MsLockYourPosts
MsLockYourPostsVolunteer in reply to gemit2000

Don't count on treatment giving back your immunity! In the time that I wasn't getting IVIG because of COVID my IgG crashed to 125. I have been in a solid remission since 2015, when I got my last treatment.

if you read captain ron's last response to me I learn that treatment is hard on B cells no matter which treatment so he said what you did. don't expect an uncompromised immunity... better ALC, RBC, Plt & Hgb, but still immunosuppressed.

I hadn't had IgG tested in 2 years, nor IgM & IgA in 4, so this summer I was surprised to see IgG had been cut in half from Dx (though still hanging onto to normal @ 700+, but the other two had gone through whatever the opposite of the roof is (fallen through the floor I guess).

Asked the doctor could I have my immunity improved with IVIG and he said it didn't work like that. I then said I read IgM (or A?) was important in creating antibodies for a new pathogen like Covid and he said if that's low IgG is sufficient so not to worry. He added that not having had a single infection since Dx and getting through all the cuts and scrapes that got filthy in the dirt plus healing up 5 surgeries including coronary bypass tells him more about my immune system's ability to work with what it had.

But God bless your remission (solid remission much better than solid tumor)

Be well, stay healthy and thanks for your time and assistance

MsLockYourPosts
MsLockYourPostsVolunteer in reply to gemit2000

Have you had your IgG level tested?

Have you considered getting a second opinion regarding treatment? I have the same markers and went almost 22 years before beginning treatment. Although I felt fine and was asymptomatic, my local oncologist convinced me to begin treatments after having had double pneumonia and then food poisoning that wouldn't go away. I didn't do well on ibrutinib, so my husband and I opted to go to MD Anderson in Houston before shifting to the next treatment option. The specialist I saw there was very diplomatic, but reading between the lines, I could tell he felt my local oncologist had been a bit premature in starting treatment. Yes, my white count was around 100,000, I was slightly anemic, and had had the 2 hospitalizations, but he didn't feel that was sufficient reason to start treatment. I have been on Venetoclax for almost 2 years and am doing well, but I wish I would have gotten the 2nd opinion from a specialist before agreeing to treatment.

gemit2000
gemit2000 in reply to Lisa-1959

Funny but I was on the way to see if I CLLSociety.org had this '2nd opinion program' I seemed to recall when I saw your email. So yes, looking for some consultation. But after the reversal of #s on my 10/8 labs I don't know what my doctor will say now. Of course, he might reverse course & decide no course of action is needed on a course of treatment.

So should I start Tx. I'll find out for sure what my 'first opinion' is next week. But I'm gathering from your experience you may lean toward waiting. I was leaning toward starting, feeling that V+O seemed to be a relatively low risk way to get rid of the approx. 1/2 trillion cancer cells floating around (if I figured the math right, if 100K is 100 billion/L & you have 5L of blood). Seems not ideal. And there are risks to doing nothing, like increased risk for secondary cancers, anemia, increased infections (in 8 years for me, 2 teeth). With Tx, I'd hope to reclaim healthier immunity & possibly more vigor from an increased RBC and HgB .

I started reading through the updated IWCLL (2017) though and found that given my current status, even with my "bad" results in Sept, there is nothing indicating Tx there. Only the 10.0 Hgb indicates Tx, but saw if that's the only issue they recommend treating the anemic not the CLL. But I'm left wondering if even the updated version is a bit antiquated given more and more proof of safety and effectiveness.

On my other front, testing, I've yet to find is any agreed upon standards as to which tests for which patients are indicated. From Aussie Neil above I do understand there is no matrix of standards for pre-testing based on which markers one, but most have mentioned genetic testing as important to guide Tx decision as far as dosage and duration even if you're headed for the novel targeted agents.

complicated!

Lisa-1959
Lisa-1959 in reply to gemit2000

I know the testing is important to determine bone marrow involvement plus the genetic markers which help in determining treatment options. My blood counts have also fluctuated...even dropping back into normal ranges before starting to climb again, so a one time bobble isn't necessarily an indication treatment needs to begin. In 1997 when I was diagnosed, a white cell count of 100,000 was the trigger for beginning chemo, but now the decision is based on the totality of blood counts and symptoms.

Since I have been on the journey a long time, the standard protocol has always been to not treat too early because there is no cure for CLL and remissions didn't last very long. Granted, remissions are significantly longer with the targeted drugs and a cure does appear to be on the horizon at least for some CLL patients, but I haven't read anything that has specifically changed that watch and wait protocol. I am definitely not an expert on this disease...many on here are vastly more educated about CLL than I ever hope to be, but I do think the 2nd opinion is a good idea.

gemit2000
gemit2000 in reply to Lisa-1959

weighing the risks of starting Tx vs. quality of life issues has changed over time. You've been in almost 3x longer than me but when I began I recall CLL symptoms - like fatigue, aches, fogginess, sleep issues - was something you'd live with. Then comes Ibrutinib and Venetoclax and symptoms are now 1 of the 7 factors that indicate treatment. However, I have an indirect CLL symptom that is nothing they've addressed; being immunosuppressed during Covid means that I have to take extra-ordinary precautions. However, with Tx I have an opportunity to strengthen my immune system enough to be able to follow precautions of the general population.

For me this IS a health issue being 1 of 5 members of an over 100 member senior softball league who was unable to rejoin it when it restarted. It was what contributed most to my physical and social-emotional health. Instead I'm isolated and I fear deteriorating physically and mentally, while I can see a Tx right there waiting for me that can potentially put this all in a rear view mirror & yet I wait for it. The patient's become impatient.

I am clear now that my doctor decision to treat jumped the gun even based on the poor results of my Sept test. And it's crystal clear he'd be defying the IWCLL standards based on the totality of my tests of he last few years to which I would say: go ahead, "jump"; "defy"!

thanks for taking the time.... kind of you

Lisa-1959
Lisa-1959 in reply to gemit2000

I wish you the best in whatever direction you and your doctor decide to go. Even though I have been on Venetoclax almost 2 years and feel great, my oncologist still doesn't want me out and about. My white cell count and neutrophils are below normal, so there is still concern about my immune system not being able to fight off Covid. Sooooo...I am sitting at home, too. :-(

I can only speak in generalities, but if I understand that your Hgb is back up to 13.8 from 10, lab error needs to be considered. In any case, treatment no longer seems urgent. I would join the chorus that getting a relationship with a CLL specialist is a very wise next step. You have time. I drive 900 miles one way every time I see Dr. John Byrd at OSU, in Ohio. You can find a specialist closer I am guessing.

Again, generally, non specialists treat earlier than specialists. There is NO data supporting that earlier treatment results in better outcomes or longer survival. Also, all treatments for CLL can be life extending compared to no treatment and in many cases improve quality of life regarding energy and reducing node size and spleen size, therefore physical discomfort. However, all current CLL treatments try to kill all or almost all B lymphocytes which are the cells which make immunoglobins or antibodies. Your immune system will not be strengthened in a significant way although some patient’s IgA may stabilize on BTK’s, IgG (the most important immunoglobin) will continue to track downward after treatment. All new immunoglobins are made from B lymphocytes, no B lymphocytes no new antibodies. Under the current state of medicine CLL and it’s treatment translates to immunocompromise.

Also, your first treatment choice is your most important decision as it will affect what your second treatment might be if it becomes necessary in the future.

Take time, read all you can. The CLL Society website is a fountain of highly reliable medical information on this disease. It’s founder, Dr. Brian Koffman, a retired family physician has had CLL for over fifteen years and CAR T was his fourth treatment.

Get a specialist. If your local hematologist is offended by your desire to consult a specialist, you may have the wrong doctor. He should support your desire and enthusiastically work in collaboration with the specialist.

Take time. Knowledge is power. All the best to you.

as I just wrote someone, I had contacted Dr. Chanan Khan, Mayo Clinic Jacksonville, 2.5 hrs from me, a few years back and he wrote back that when time came for Tx he would take me on. I had let that thought go when thinking the new doctor I started with a year ago (and the one I wanted when diagnosed in 2013) could have enough expertise to avoid the hassle. I can imagine doing all that travel to get the same V+O I'd get here. But I'm sure you're right that the Specialist would know more and have a more nuanced approached about when to test, what to test, dosages to adjust, durations to adjust, et. al. I thought the doctor who I'm with, who was referred to me by a patient and who was the only one at Orlando Health who listed leukemia as a specialty and conducted at least 1 or 2 trials, could be my 3rd and last doctor. But I thought of what you said, whether Tx is in the offing, it's certainly not urgent and yes another reply on this thread was totally sure the Hgb @ 10 was a definite lab error - obviously knowing lab procedures he detailed what had happened (another strike against current doc jumping the gun & not knowing a likely error occurred and in any case not announcing a treatment plan and estimated date until he retested that number)

I have no reason to doubt your knowledge about new treatment's affect on B-cells. It saddens me to learn about this suspended state of immunosuppression. Immunoglobulins were one of my concerns as I first learned from a recent test my IgA & IgM had gone through the floor while my IgG was hanging on to 'normal' but had been cut in half from 4 years ago. Another revelation to me was that I asked him about IVIG to strengthen my immunity and he said it doesn't work like that. But... said that not having had almost a single infection since Dx and having been able to ward off whatever attacks us from days to day. From the dirt and the cuts and 7 yrs of dog ownership and healing from 5 surgeries including heart bypass, tells him so much more about my immunity than IgG levels.

But on your point of Tx not helpful to B-cells and so not helping one's immunity, perhaps the health of B cells I'm guessing is more determinant of immunity health than immunoglobulin levels. Cause I have a local CLL friend - met on this site - diagnosed at same time with similar markers but had CLL symptoms that had her fighting for Tx. Finally got Kipps in San Diego to treat her with V monotherapy and as of last month she's MRD 'maximally' undetectable... and I swear she told me all her immunoglobulin #s are back up to respectable levels after I shared mine are sinking. But in case l'm just starting to make things up (as sometimes you do when the culture says it's fine to make things up... you can even become President) I'm going to contact her and double check. I guess you're saying, at least in the time of Covid don't expect to break out of your immunosuppressed label and join the general population with their general Covid precautions. Sad for me cause I was hoping to be able to get back to playing softball, which had been the main thing contributing to both my physical and social-emotional well-being. The thought of early 2021, when the doctor said my numbers could be approaching normal, as the time I could possibly rejoin the league that I joined a week after my CLL Dx to satisfy the exercised portion of my hem/onc's 'guide to living with CLL, was keeping me going. But I guess you're saying I might want to adjust that schedule instead for when the country stops going viral.

Lastly I actually spent hours with Brian Koffman today connecting to his Global Forum 12 to 5 EST. Also replied to his post about his choice of V+O for Frontline being his #1 pick for ASCO 2020 abstract with all of these questions (figured he had enough to do so I told him please don't reply to me until doing so is not stressful... yeah I do know and am amazed like you by his battle (pretty damn impressive, huh?). Further I linked to his Treatment Tool with 5 Experts. A little thin (someone on this thread told me that, maybe you) but 4/5 did opt for V+O given my data, with 1 of them saying to 'consider acalabrutinib' for easier regimen, and surprising 1 advising BR with 2 saying 'consider BR, which I wouldn't consider. On top of that I read and listened to experts on "Test Before Treat" wrote a couple of questions for "Ask the Doctor" and signed up for "Expert Access" to get a free consultation. So you might have picked up I'm definitely on the same page as you with Dr. Koffman and his site (filled out forum survey extolling his virtues)

Alright, don't know if first I thank you first or apologize for taking up all your time and energy, but if you're still reading I've taken advantage of your concern and your support. Thankfully for you I'm getting punchy, but you can tell by this reply and almost all my other ones I'm telling you the truth about losing my social-emotional well being after losing softball and close to losing it in general while I take the lack of social interaction out on everyone here who was nice enough to join this thread.

Thanks for your knowledge and concern. Stay healthy and stay sane at least for a few more months until this insane year of 2020 ends. Nice meeting you.

AussieNeil
AussieNeilAdministrator in reply to gemit2000

With respect to the possibility of immunoglobulin recovery during or post treatment, chemoimmunotherapy (e.g. BR, FCR), can have a lasting impact on immunoglobulin counts. You need the recovery of both B and T cells for immunoglobulin counts to recover. Monotherapy treatments continually reduce B-Cell counts, but at least with Venetoclax, BCL-2 is over-expressed in CLL, so some healthy B-cells might survive. Limited time combination targeted/inhibitor therapies theoretically should allow healthy B and T cell counts to recover post treatment, hence immunoglobulin counts are more likely to also recover. We've had a few members on non-chemo treatments report immunoglobulin recovery, even into the reference ranges, so we shouldn't give up hope of improving immunity after treatment.

CLL impacts the immune system multiple ways, so even during treatment, once the bone marrow has sufficient clearance to overcome the bone marrow suppression due to the treatment drug(s) and accompanying prophylaxis, our overall immunity is likely to be better than it was prior to starting treatment.

Neil

Thanks for your reply gemit,

You must know Carol, Meliora Day. As you say she trekked to San Diego for years and worked with Dr. Kipps who resisted her request for Venetoclax combined with ROR1 blockade. Dr. Kipps preferred monotherapy with V and did get her to MRD undetectable. As Aussie Neil adds below. Time limited treatments with BCL2 inhibitors can spare enough healthy B lymphocytes as BCL2 is over expressed on CLL B lymphocytes, so they are the first to succumb to Venetoclax. After treatment, if the marrow still has B lymphocyte progenitors still around, new healthy B cells could be propagated and immunoglobins created by the plasma cells begat from mature healthy B cells.

Stay well, get smart care, well researched care and you will play softball again.

Ron

One last comment.

I am glad that you “tuned” in to the CLL Society forum yesterday. A lot of good current info on the basic science and current treatment options. Much easier than traveling to a big center, hotels etc to get a wonderful update on where things stand. Yes Brian, having started his journey earlier than us has had treatments that whacked his healthy B lymphocyte stem cells so for him and anyone on chemo or long term BTKI’s a recovery of immune function is unlikely.

The biggest risk of monotherapy with Venetoclax after TLS is eliminated is long term neutropenia which, in the era of covid, is a daunting risk.

We are in Maine and are coming down to Fort Pierce to launch our live aboard winter home next month.

Take care, Ron

Enjoy your snowbird experience. Sounds like an enjoyable way to spend the winter, floating on water instead of buried in snow. I can't relate except for having a water bed during the late 70s. Hopefully your location on the water will keep you isolated from this land of Covid, that may promise to be the land of spiking Covid during the fall and winter. Have snowbird friends who've come down from Canada annually to play in our softball league.... except for this year. I thanked them for the solidarity for each of our risk averse decisions. But mask up and you'll be fine. I assume most of our cases are due to people not being careful. After all, it certainly can be Flori-duh.

We have usually gone to the Bahamas, which are now closed because of destruction from Dorian and also Covid. We’ll probably be down in the keys hangin’ out away from folks mostly.

Oh wait, I had one last comment I forgot to add too. So what's the deal with my immune system when I have ALC pushing 100K, IgA & IgM looking fairly shot (with IgG is hanging on to normal levels @ approx 700, although at least cut in half since Dx), yet....

never had an infection since Dx (one tooth actually) and have had plenty of encounters with sniffly fluey people, have had plenty of cuts that spent hours caked in dirt, had 1 major and 4 minor surgeries and avoided infections through everything. Why does my immune system seem to be just as healthy as prior to Dx?

I've often said if I was the type who only went to doctors when something was wrong, I would not be aware I had cancer for 8-10 years.

Take care

My IgG gM and gA are similar to yours, my ALC is 100,000. Some patients have ALC’s as high as 800,000 even > 1 million and have not yet been treated if other blood products remain adequate.

Answer is IgG is your heaviest hitter and is still in the game (barely) in a year or two your/ (my) luck will likely run out. This is a good time to get your relationship with specialist that you can relate too and trust lined up. I would wait to treatment time in a panic.

wish my doctors were as sharp as you. She is the one I want to double check with about her immunoglobulin levels and her immunity. You even know about Kipp's planned trial with ROR1 blocker, which I first read about ROR1 in 2013 on Chaya Venkat's site seemed to this layman that that should be the target and not CD20 (only CLL cells had it, no?)

After checking with her I think I need to check out a book from the library to study the immune system. I get lost with the B-cell parts and the T-cell parts and the immunoglobulin A, M, G et. al. , antibodies, cell surfaces, cancer cell surfaces, virus cell surfaces, progenitor, etc. Probably need to review the who system with stem cells, plasma cells, lymphoid, myeloid (myeloid sound like how I feel about all this science, a combination of 'my lord' and 'oyyy').

But I'm a bit more encouraged from this and Neil's explanations (though still need somebody to explain the explanations or at least reread them a few more times; Carol may get that job).

Thanks again for your time and understanding (both of my situation and the science)

AussieNeil
AussieNeilAdministrator in reply to gemit2000

CD20 is expressed on healthy B-cells and on a subset of T-cells.

gemit2000
gemit2000 in reply to AussieNeil

and since Gazyva is a CD20 monoclonal it would therefore also affect some (most?) healthy B-cells too? Am I getting that right? So it seems to me R and O help fight the cancer but also have adverse effects on the B-cell and, if I recall,l ROR1 is on CLL cells but not B-cells so using a mAb specific to ROR1 wouldn't have that adverse affect?

AussieNeil
AussieNeilAdministrator in reply to gemit2000

Yes with respect to CD20 MABs such as Rituximab, Obinutuzumab and Ofatuzumab. See CaptRon1976's comments about ROR-1, for which we don't yet have much in the way of trial data.

Neil

Your are more than welcome.

en.m.wikipedia.org/wiki/Hae...

This chart explains a lot about where various blood cell lines come from.

Basically in your bone marrow there are myeloid stem cells that propagate into platelets, neutrophils and red blood cells. Then the lymphoid stem cells whose job it is to differentiate into the lymphocytes, T cells, NK cells and plasma cells. This is the line of cell development that is our biggest threat. Also, unfortunately, because it is so complicated, the CLL drugs target the bad lymph cells begat from the lymphoid stem cells, but they have “off target” effects which disrupt production of the progeny of Myeloid stem cells which causes anemia neutropenia and thrombocytopenia.

It is gigantically complicated and can be frustrating. Don’t let that get to you. You don’t have to be an expert in all human diseases. But you can train yourself to be an expert in the one disease that is such a threat to you.

The library is good for the very basics of blood formation. CLL society archives will teach you a ton. NIH, BLOOD and many journals online will help. HealthUnlocked is packed with wonderful archives to answer any question you can think of.

I thought/hoped ROR1 was the holy grail since it had the potential to kill only malignant or cancer B lymphocytes and totally spare the normal ones. This would cure the disease and leave our B lymphocytes alone to protect us day by day and when they mature into plasma cells they would in turn make our necessary immunoglobins whose job it is to make antibodies.

As it turned out it wasn’t quite that simple as ROR1 is common on many embryonic cells which when we humans mature they disappear which is good, and also mostly ROR1 is mostly only on CLL B lymphocytes. Problem is that ROR1 protein is also on the cell surface of some healthy normal organ tissue and so off tumor toxicity’s make using an ROR1 blockers risky.

The more you know, the less you kvetch.

Carol would be a great resource.

What is your ALC now?

What was it 6 months ago?

What does your fish test tell you about your gene that has deletion, 13q? 17p? 11? 12?

What is your mutation status? Mutated, unmutated?

Take your time, hire an expert. If not at Moffit then up in Jacksonville. Don’t go with hat in hand. Go with knowledge.

“Smart Patients get Smart Care,” B Koffman, MD

Best,

Ron

will respond if needed but I'm signing off, off to my the B'day celebration of me and my Mom - me Oct 5 '54, she Oct 16 '24 - and so together we created our own shared October 10 1/2th (hard to pronounce) celebration. I'll also add that when it comes to health, she just shames me (I'm up 6 to 3 in # of specialists needed). Perhaps I was named after her good 'Gene's but sure didn't get many of them from her; seems I got most from the other progenitor.

For a few years I was a full time student, then more part-time until I dropped out in 2018 when a new course of study began finding that I had arteries 100% & 80% blocked. A bypass later and a seemingly plateau (after a year long downturn) in my CBC #s and my cancer study days were over. Of course just like when I took science in school, my depth of learning only would have served to ace any test a HU CLL member would give me (if I crammed). But any understanding I had that was slippery enough back then has long since slipped completely from my grasp. I don't have the "velcro" for scientific concepts... never did.

But I have always been an 'I want to know' person, not a 'whatever you say doc' person. Each of my oncologists barely tolerate me and all my questions and thoughts concerning what I'd read. My first doctor said to stop that cause it only caused anxiety. I told him ignorance and blindly following made me anxious. I fired him for that and when in 2015 he told me to be ready for Tx this year, based on one ANC outlier. That and his adamance he already decided on my Tx, FCR, while I continuously came in to bring up the positive results of BTK & BCL-2 inhibitors. When I did that he was the one who was anxious

But after telling me how stable my disease was a year ago, my new doctor blindsided me with this decision to treat and suddenly I was on every website, reading all sorts of medical journals, registering for forums, and asking everybody everything so I could try to get back to learning and relearning at least enough to avoid having my doctor silence me then sell me on whatever he decided on the 15th. . I now have some clearer thoughts of where I am and how when and what options may be best going forward. My main takeaway is that his original declaration that Tx should start mid-October is on indefinite hold. Mid-October will only be used for a discussion of Tx options as I see no urgency whatsoever, though it may be time to map out the future by looking at various scenarios affecting possible Tx options and outcomes.

In the meantime I am due to have a CLL Expert contact me in 2 to 3 weeks after be accepted in the Expert Access program. As well I just put in for a special ppwk authorization with my ins. co. to allow me to see Chanan-Khan in their Jacksonville area network though not listed in my local geographic network. So I'm optimistic I will be able to see him if he will take me on as he said he would 3 years ago.

So thanks for being part of my re-introduction to the study of blood cancer. My gut tells me though I might just wind up dropping out of these studies again, cause I'm feeling come Thurs my doctor will say "never mind... looks like Sept's CBC contained some invalid results. So for all I know it'll be another 8 years before another Tx surprise arises. But to answer your questions in case you really want to know, my ALC was 95 in Sept and last week 85. In 2013 it was 9 then went up 50% per yr for about 5 years to mid 60s, but for the last 3 it has bounced around between 55 & 95. 6 mos ago it was high 60s but the year before that it had been in the 80s. In any case doubling time, never a factor. I'm 13 q del (partial deletion including DLEU1, 69% of cells). IgVH. 5.08% mutated w/clonal population 5-51 (never knew the implications for % mutated or the type of population... or WTH >2% mutated compared to germline sequence meant so after asking just ignored and just said 'mutated')

Ok, I'm sure you've had enough of me (I've had enough of me).

Onward! and thanks for all, Gene

Good for you, Gene.

You have been in a deep dive into medicine for a while now I see. I think you are right, your markers and numbers suggest you have time and who knows if we’ll ever be treated.

Happy birthday, another parallel, my mother is 96 in a few weeks. She is fine and living an active life in Toledo and just had two new water colors accepted by an esteemed art society there. She drives, she cooks and is totally busy. Like yours, I wish I had her blood or more of it as half of what I have is hers!

Anyway, keep on keeping on, as they say.

I’m here if you want to talk.

Ron

Wow! We should get our two amazingly youthful 96 year old moms together, though like me having to reteach myself science over and over, I also have to reteach her the internet over and over (even though I know her 5 year old great grandchild would be a better candidate for that role).

She had been the designated driver for her nonagenarian posse toting 90 and 92 yr old youngster around but we're both in agreement night driving and highway driving is done and I taught how our Medicare Adv Ins covers free rides to the doctors. But so grateful like you in seeing how great Mom is doing.

What's the 1976? For me it was my senior year in college or maybe you're just patriotic including the bicentennial... or maybe your just incredibly advance in the computer sciences too, and like my gemit2000 signifying when I first had my own email account, that was the year for you (in '76 I was taking a BASIC and FORTRAN course with punch cards and a computer that took up an entire room).

Appreciate you

Gene

Not terribly exciting.

It is the year our live aboard was built. It’s part of the transom serial number.

Cheers

We are progeny of our parents. Our parents are our progenitors.

bkoffman
bkoffmanCLL CURE Hero in reply to gemit2000

Thanks for the kind words. Nothing really restores our immunity, maybe a transplant. Ibrutinib may or may not help a little with IGA and some fewer infections. IVIG definitely ups the IGG and reduces respiratory infections in the right patients. The treatment tool has flaws and we had little input, but it can give some helpful suggestions. It's already out of date. Expert Access is a great option. V+O, I like that choice. Stay strong, Brian CLLSociety.org

gemit2000
gemit2000 in reply to bkoffman

Would love to get your opinion concerning my 2 main questions about my treatment decision and necessary "Tests Before Treat" which led me to this site and yours with my upcoming hem/onc visit on Thurs. I'll try to summarize either today or tomorrow as right now I'm off to my Mom's 96 year old birthday celebration ( healthwise she makes me look silly but outliving her entire generation it's left to us nextgens to be there for her, with me the only one there geographically as well as spiritually.

Thanks for yesterday and the incredible service you provide to us all. And of course I as I've stated on previous questions to you that I, and I'm sure most, understand if you don't get back to any of us individually with all you have on your plate.... despite your superman warrior status.

Thanks for your immune response above and wishing yours stays strong as can be (mutated Gene)

bkoffman
bkoffmanCLL CURE Hero in reply to gemit2000

Mutated is good. I will try to help if I can.

Sorry... I know that could be my outcome but since my disease kept getting worse it did so indolently and I never had symptoms and had favorable markers so I figured the one two punch of V+O could possibly get me back all the way. A bit unclear what marks one as immunocompromised. My IgG is still hanging on to the normal range but the IgA & IgM which I heard would be important in creating Covid antibodies have long since gone south. But I haven't gotten 1 darn infection since 2012 except a tooth - no colds no flus, barely a sniffle and my immune system has also seemed to handle my 5 surgeries (2 knees, 2 hernias and one open heart bypass) plus every little cuts, scrape, dirt in the eye and 7 years of dog ownership with flying colors, which my doctor had said is what's important, not immuno-globulin levels.

All this to say, this self-data gives me hope to get back to normalcy. Less hope about my country.

Will just add that I had been focused on a fellow CLLer from where I am, Orlando, who with similar markers got V monotherapy (also discovered over the decade developed complex karyotype on FISH retest) and after a year or so her # s looked great and then it took 2 1/2 more years till last month she learned she was the most MRD undetectable there is in 2020. So she's done with Tx and she's back out and about... as much as the virus will allow. This is what I had in mind and what I've told my body is expected of this, but in 2 years max. 😊

Ok.. have taken up far too much of your time and strained your eyeballs too much too.

Nice meeting you and thanks for your input and support. Well appreciated.

gm

Your doc seems to believe that V monotherapy is your best treatment option, regardless of your present, unconfirmed mutation status and regardless of whether, by the book, you are ready for treatment. Personally I would not be comfortable with that assessment and on both counts would seek a second opinion. But even if you want to push ahead with tx, surely there is nothing to lose and everything to gain from an up to date FISH test? For certain mutations, for example, current evidence would favour tx with BTKi +/- rather than V mono.

thanks.. I agree that not only doctors should do no harm but FISH would do no harm and as well the 2nd opinion, having signed up for the Expert Access program on CLLSociety website, and I'm likely to call Mayo Clinic Jacksonville having corresponded with a CLL Specialist a few years back who said he'd take me on when the time came. The biggest question now is do I push through with Tx now that the 2nd test definitely does not indicate need (nor really did the first one).

Note: BTK's no good for me due to heart issues, my IgVH is mutated, & Doc wants V+O and the Treatment Option Tool I used on CLLSociety site pointed to that as well

From what you describe neither your CLL symptoms not your bloods indicate treatment now. Maybe your present Dr's view on timing (as well as choice of drug) takes into account your heart condition?

Anyway a second opinion and a second FISH should resolve any doubt. Best wishes.

agree... I was told about his Tx plan on a 3 minute phone call so will find out better on visit next week. But on that call the one thing he mentioned was he didn't like the Hgb, which was 10.0. IWCLL says @ 10 and below it would indicate Tx, but they also say if that's the only indication, then anemia should be treated and on top of that everyone says you don't make a decision like that on one test... which on the next one showed it was 99% likely a lab error when it was 13.8. So for a host of reasons I think he got it wrong..... BUT... I'm weighing out the risks/rewards of Tx anyway, if any Dr. will agree to it, if it could get me to a better place.

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