Frequency of MRD testing post trial

[Catnap7]

My I/V trial ended one year ago. Dr Coutre, my Stanford doctor never ordered MRD testing the entire year. Now the PA I was given wants to have one every four months. I am curious to know if this is a common protocol when you are a year out of trial and/or what might be the reason for the frequency? Nothing has changed in my blood work. Catnap7

[AussieNeil Administrator]

Sadly you can no longer check with Dr Coutre, but as part of your clinical trial documentation, I would expect that you would have been informed of what testing would be done and when. In my clinical trial, I've had one uMRD test three months after stopping trial medication, with immunophenotype flow cytometry testing about the same frequency as you. It's not as precise as uMRD testing, but it is checking for the return of B cells and whether there's a clonal B cell population.

Congratulations on your first post! Did you intend to post unlocked?

healthunlocked.com/cllsuppo...

Neil

[cajunjeff]

I would think mrd testing varies from trial to trial. It’s not an invasive test so I would be fine however often they want to do it.

I have just added venetoclax to my Acalabrutinib outside of a trial. I think my doctor will test for mrd quarterly. If I do reach mrd negativity, I think the plan is for me to stay in venetoclax for an additional six months and then stop all Cll meds assuming I stay mrd negative.

[Catnap7 in reply to cajunjeff]

Thanks for your reply. Best to you and on reaching MRD negative !Catnap7

[E-Lynn]

Dr. Coutre was my doc as well. I imagine you are seeing John Michael Conte who came with Dr. Tait Shanafelt from Mayo and who is very knoweldgeable. (Were you at the CLL Society support meeting a month after Dr. Coutre's passing? Shanafelt was there and spoke higly of John who he brought with him from Mayo when he came to Stanford.) MRD testing at Stanford is just a blood draw. I was on Venclexta for 4.5 years, as mono therapy, and asked to have the MRD test 18 months into my treatment. I was MRD- by flow then. Dr. Coutre recommended I just keep taking V as I had no side effects and it was being provided free of charge by the Genentech Access to Patient Care Foundation. I had to go off V this July when my platelets crashed with ITP. Except for my platelets, my labs were normal although my ALC was below 1k, as it had been throughout my V. A month ago, I had the MRD test again, and had a few rare cells that were thought to be CLL, but not enough to quanitfy. In several weeks, I will get a BMB and MRD and FISH testing will be done, along with any other study that may be shed light on why my immune system seems to gobble up my platelets.

Long story short .. MRD testing is very valuable.

And Stanford is in flux right now, as a search is taking place to provide the kind of expertise that Dr. Coutre provided to all of us. Dr. Shanafelt has impressive CLL background from Mayo, but he was brought in to run a new physician wellness program, now especially important as docs burn out in these COVID time. I'm hopeful Stanford will bring in a CLL expert for all of us, as UCSF is more lymphoma-centric (Kaplan) and there doesn't seem to be the focused research there or trials that Steve Coutre ran. I miss him, a quiet, kind, knowledgeable presence. I first saw him in 2009, then began my medical safari trips to the NIH 2010-2014 (Natural History Study, Ibrutinib trial then lung cancer surgeries there), then another safari to Sharman in Eugene OR in 2015 (mono gazyva), then a return to Coutre in 2017 when Coutre put me "off label" on Vencelxta. (Well the "short" became just as long in the end.)

[Catnap7 in reply to E-Lynn]

I did not know about the CLL meeting, or I would have been there. Happy to know more about Dr Conte background. Thank you for all the information. Yes, Dr Coutre was a wonderful person, and he alone took all my worries away. I miss him alsoThanks, and best to you!

Catnap7

[richutchens]

I have one every 3 months. I’ve had one every three months since 2013. I go to Mayo Clinic in Jacksonville Florida USA.

[Catnap7 in reply to richutchens]

Thanks, Now I am beginning to think MRD testing is just up to the Hematologist when they feel it should be done.

[johnliston]

I was in the I/V trial at M D Anderson and they want to check MRD in blood every 6 months since the trial ended.

john

[Catnap7 in reply to johnliston]

Appreciate your reply!Catnap7

[Smakwater]

As I understand it Catnap, the primary purpose of MRD testing is to measure efficacy with treatment, rather than durability, therefore clinical trials are usually weighted to a measure of reaching MRD.

Durability monitoring MRD is costly, the technology is not commonly available to the general medical community, and the early identification of relapse disease has not yet improved second line treatment to the point that the IWCLL will change the protocol.

Aside from my specialists biannual peripheral blood labs, I have a CBC run every 3 months at a local lab for $20.00. in which I monitor my own progressive status.

Even if disease progression is revealed during the 3 month monitoring period, the questions still stand -

1. What is the best treatment, and why?

2. When do I begin that treatment?

3. What if the choice of treatment fails?

I think it interesting that your PA is willing to request MRD testing to monitor your remission durability. If the cost of MRD testing is reasonable or covered by insurance, I would certainly entertain the idea just to have the measure of precision.

I am thinking that the weight of consideration is more to the options of secondary treatment. Consider asking the doc what their idea is on that subject.

If you do, please get back to us with the outcome. I for one am very interested.

JM

[Catnap7 in reply to Smakwater]

I do understand it is to measure the efficacy. They did the testing at the end of first year at which time, I became MRD negative as well as at the end of 2nd year of trial. I have been getting blood tests every 4 months since then and there doesn't seem to be much change. Since my first two MRD testing were paid for by trial I asked the nurse about the price (I didn't know if it was the same as a CT scan). The answer I got was we don't have to do it so often if you are having financial difficulties That got me confused. I had a virtual appointment with the PA a few weeks ago and he did bring up my 11q and appropriate drug for future, if necessary, Anyway, thanks so much for your help

Catnap1

[Smakwater in reply to Catnap7]

The dynamic in CLL treatment has provided much encouragement in recent years in spite of the challenges with Covid.

Keep us posted.🎯

[lankisterguy Volunteer]

Hi Catnap7,

-

Like E-Lynn 's comments above, I started on Venetoclax in 2016 - off label, and at that time the MRD test was new and required sending a blood sample to an outside lab, so it required a special effort (and I assume high cost). -

By 2018 Weill Cornell NY Presbyterian acquired the capability to run the MRD test in house, and it only required one additional tube of blood to be taken (and that may be because a part of the pathology department runs that test instead of the blood lab).

-

Since 2020 the MRD test has become routine with my quarterly blood testing, and apparently no special effort is required. So it has become one more routine data point like ALC and platelets.

-

So what you may be seeing is an evolution in testing procedures / cost vs. any change in your particular care or CLL condition.

-

Len

[Catnap7 in reply to lankisterguy]

Len, thank you so much Alot of my confusion was I thought my MRD test was done by BMB because it was right after that Dr Coutre would call me with the news Ok, I realize they will be doing it by blood test the same as checking platelets Perfect! That's a good thingThanks for clearing this up

Catnap7

[lankisterguy Volunteer]

It can be done in the bone marrow- and the marrow version is more precise / rigorous, but the blood version is a good analog / indicator. The marrow version is primarily reserved for research like clinical trials or possibly a final check before pausing treatment.

Len

[Catnap7 in reply to lankisterguy]

Thanks again

[Catnap7]

Yes, I certainly get the flip side also!

[cajunjeff]

I think I am nervous to some extent every time I do labs. I would not think, outside of a clinical trial, frequent mrd testing would be needed for someone lucky enough to get to mrd status. Regular labs would pretty much tell the story. If your lymphocytes start creeping up, that would be a sign that cll has returned which could then be verified by flow cytometry.

[Justasheet1 in reply to cajunjeff]

Jeff,

I echo your sentiments about MRD testing. My local doc does a Flow test on me every three months with the other labs.

I’m on Ibrutinib and never saw the point until I hit mrd on a flow!

I send it all over to Dr Wierda. I’ve now been mrd- in the Flow for almost two years and he’s intrigued. He said that he will do a uMRD test at Anderson on my next visit.

I always planned on adding Venetoclax at two years but then Covid screwed everyone.

Wouldn’t it be awesome if just obinutuzamab and ibrutinib got me to negative and I could stop the ibrutinib?

I probably would need a bone marrow look but it would be incredible if I could get there without the Venetoclax and save that for later.

A guy can dream can’t he?

Jeff

[cajunjeff in reply to Justasheet1]

That is awesome news. Its important to remember that the end game is not mrd negativity, but overall survival. I am adding venetoclax to acalabrutinib which might get me mrd negative. But even if I get there, there is no guarantee how long it lasts. My overall survival might have been better staying on acalabrutinib until it stops working and then sequencing to venetoclax.

I dont think getting to mrd negativity on a btk drug combines with a mab is typical, but it happens. Why shouldn't you be one of the lucky ones. Thats so very encouraging.

[Catnap7 in reply to cajunjeff]

Well they don’t seem to be creeping up yet but truthfully I’m nervous about it. Being off drugs is heaven for me Nothing hurts no matter how hard I work out and I’m not confined to the water anymore Hopefully my remission will last but if it doesn’t I’ll just have to dodge drug side effects again Catnap7

[Mldeterm]

As others have said, check your trial paperwork. My husband was in I+O+V trial and only had one post trial BMB to verify uMRD. There is no further marrow testing, only blood going forward. Good luck!

[Catnap7 in reply to Mldeterm]

Thanks !

[schmitthj007]

Typically in a trial testing for MRD is pre-specified by the trial protocol both for testing in the blood and bone marrow. Trials may also include CT to check for spleen size and lymph nodes.

You can look this up in the copy of the protocol you should have received but a research nurse might be able to clarify this for you.

At Dana faber I am tested every 3 months (blood only) for MRD for at least 3 years after stopping medications. It is a bit nerve racking every time I go to be honest and waiting 2-3 days for the results.