UMRD redults

[DGG1931]

I just received my results from the uMRD test that I had this week at MDAnderson. My results from 3 months ago went from 0.01 to 0.007

I have been treated with Calquence since 2/2020 and added Venetoclax on 2/2022. The plan was to stay on these 2 drug combination for 2 years and hopefully be able to come off treatment if labs showed remission.

Does anyone know if this most recent level would be acceptable for me to do this?

My doctor Dr. Ferrajoli has ordered a BMB at my next appointment in February at my request to check the MRD status in the bone marrow. But she seems to be much more hesitant than Dr. Thompson was. I sure do miss him.

[Jm954 Administrator]

I would definitely wait for the bone marrow results before making any decision as the sneaky little CLL cells can hide there when the peripheral blood looks good. With your blood results I think I would be staying on treatment a bit longer to aim for a deeper response anyway.

[SeymourB]

DGG1931 -

I don't think there are standards requiring a particular level of MRD for remission yet. MRD is still more like a quality check on the remission - deeper uMRD should lead to a longer remission. They're still graphing the average TtNT (Time to Next Treatment) and PFS (Progression Free Survival) for each combination of therapy for the next 5 or 10 years. Your trial is probably part of that tracking and graphing.

I believe that remission is still defined in international trials by the iwCLL. They look for a reduction in size of the spleen, liver, and lymph nodes, improved constitutional symptoms, circulating lymphocyte count in the blood, platelet count. hemoglobin, and in the marrow, cell types.

Here's the iwCLL standards document:

ashpublications.org/blood/a...

iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL

See Table 4 and the 5.1. Complete remission and the 5.2. Partial remission paragraphs :

I think you can be considered in remission even with a partial remission.

I am on a different trial at M.D. Anderson, and am also doing MRD testing.

Via MyChart, you can post a question to your doctor asking what the requirements are for you to stop treatment.

You can send me a chat message here on Health Unlocked if you need help using MyChart.

You should also have the phone number and maybe the email of your Trial Nurse, and can ask them for clarification, too. They have a copy of the trial protocol that specifies the testing and scoring. I find that my trial nurse gets back to me quicker than my doctor does.

Since you started in February, 2022 for a 2 year duration, I think the earliest you might stop would be February, 2024. (Same as me, by the way). If the trial is like mine, there would be a final bone marrow and CT in February 2024 to decide the remission type - Complete vs Partial, and the final MRD level.

Since your blood MRD went down in the last 3 months, the next 3 months may improve your MRD score even more, and your length of remission may then be even longer.

By the way, are you getting clonoSEQ testing for MRD? It has a separate, complex report that does not appear in MyChart, although they may mention both the Flow Cytometery MRD and the clonoSEQ MRD level by itself.

Best of luck!

=seymour=

[lankisterguy Volunteer]

Hi DGG1931,

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I was going to write a long response, but SeymourB beat me to it, and IMO wrote it very accurately & clearly.

I would add on a few comments, some from Dr. Furman when I got my MRD-U 10x4 results.

paraphrasing it from memory: The MRD tests are looking at 10,000 or 1,000,000 white cells and finding too few CLL cells for the test to be significant.

Your body has billions of white cells and if one CLL cell remains, it eventually will reproduce. How fast it multiplies and when it is detectable is highly variable.

If we clear/kill all the CLL cells out of your body- you will be cured of CLL. But that probably will not happen with our current drugs.

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I reached MRD-U twice, but I went from 0.00% to 1.00% in 4 months. At that level I was technically still in full remission, using iWCLL2018 guidelines, but we restarted treatment anyway. In retrospect, I probably should have waited until I had CLL symptoms and qualified for treatment under iWCLL2018 protocol. ashpublications.org/blood/a...

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So YMMV (Your Mileage May Vary)

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Len

[Silvafoxe]

I don’t know what your diagnosis is but I’ve been told that we never get off the medicine. Also I’m surprised that they combined the two. Wishing the best for you.

[Skyshark]

You have 70 detectable cells in 10,000., That's still too high, really need to be at uMRD which is no detectable cells in 10,0000. About 30% more people get to uMRD in blood than in BM. uMRD in blood is an OK target.

[Skyshark]

Just to add.

Both short/fixed duration CLL14 trial of V+O and CAPTIVATE trial of V+I have recently published PFS for dMRD4 (d detectable), uMRD4, uMRD5 and uMRD6. Median time to progression for those that are not at uMRD4 is unacceptable. CLL14 states that there is a need for MRD guided therapy.

CAPIVATE MRD for fixed duration V+I with end point at uMRD had a number of patients that failed to reach uMRD. They continued to take Ibrutinib without V, with good results.

There is as yet no evidence that continued Venetoclax when dMRD gives better results. One person on hul reports they had no change in uMRD count after a 6 cycle extension of V to the 12 cycle V+O.

It is more common that BTKi drugs are used continuously and Venetoclax is short duration, max 2 years for most regimes.