Husband nearing completion of O+V/should there be a test for UMRD?

[lisakc1]

In just a week, my husband will have completed his O+V treatment. I was expecting some test to determine if he achieved UMRD, but none is planned. Is this the standard protocol? His blood levels are ALL in range, with the exception of absolute lymphocytes and absolute eosinophils, which remain low due to the venetoclax. Is this the standard protocol? Not sure if we should be breaking out the streamers, confetti and champagne just yet. Thank you all for your continued help and support!

[Skyshark]

MRD gives a good indication of expectation for durability of remission. It's used in clinical trials to show expected effectiveness of the drug(s).

V+O does not have uMRD as an endpoint to treatment, it's fixed duration 12 cycles and remission period is whatever it turns out to be. The CLL14 trial of Ven-Obi has good evidence regarding numbers achieving uMRD and durability of remission. The trial was fixed at 12 cycles, with no attempt to extend the duration to achieve MRD in all subjects. Because of this there is no evidence that those that failed to reach uMRD could or would if given a longer duration on the drugs.

I'm on V+O in UK, funded by Cancer Drugs Fund for "data collection". As they are still collecting data I expect to be tested for MRD but may not be. The CDF funded genotypes are the two that respond best. Unfortunately the small population (~14%) with very difficult to treat genotypes that have least durable remission are NHS funded and no data is collected. The CLL14 trials data for about half of the 14% is very limited in quality to the point of being worthless (CI ~17-97%). Data quality would have benefitted greatly from these patients being placed in CDF funding for data collection.

Some trials are developing variable duration treatments with uMRD as the end point when drugs are withdrawn. If a subject fails to reach uMRD at a fixed time point the treatment continues until uMRD is reached or progression. If and when these regimes reach clinical acceptance then testing for MRD will be required.

[Poodle2]

I think the doctors probably "don't need to test" since it is a time limited treatment and the results won't change anything. I'm sure you can ask for the UMRD test. If I understand it correctly, it is done through the flow cytometry test - that will give you a UMRD result in blood. You can also test his UMRD in his bone marrow, that is done through a bone marrow biopsy. You can be UMRD in blood but still not be UMRD in bone marrow...If I am not right, I hope someone will correct me.

As you know I finished my treatment in June. I'm having my UMRD in blood test done three months post treatment (going for it in 2 weeks). I won't be having the bone marrow biopsy done for now.

[lisakc1 in reply to Poodle2]

Hoping you are feeling much better now that you are off the meds and that you enjoy a long and deep remission! Thank you as always for sharing information and serving as an inspiration to us all!

[SofiaDeo]

I know I had it, but I have an unusual variant and treatment. There is some discussion around when it's optimal to use MRD testing, but no formal protocols that I am aware of.

RE: Poodle2's comment: There's data that blood and bone marrow are within a few percentage points at the end of a treatment. I don't recall the exact number, but I believe it was like 97%. I know with my generally marrow intensive variant, my doc was satisfied with blood NGS MRD test instead of doing a BMB.

[stevesmith1964]

I had a BMB and Flow after 240 days after O+I to confirm uMRD. I have 6 monthly flow to check MRD along with monthly bloods. 2 yrs in remission on twice daily Acalabeutinib

[Smakwater]

lisakc1,

MRD/UMRD testing is not a required measure nor standard of care in U.S. Therefore it is not likely that insurance will cover the cost. It is however, a measure of efficacy in certain clinical trials where it is most often mentioned.

Although not absolute, UMRD is a measure that is relative to better probability for longer durable remission. Having said that, one needs to define what a "durable and longer remission" is.

In my view if it is affordable and available, it provides a peace of mind that is worth the cost. Having a CLL specialist request the testing with proper coding and supporting notes is helpful when applying for insurance coverage.

JM

[lisakc1]

Thank you and I agree. I will at least ask the question, that costs nothing. We have been counting the days since treatment began. While the side effects have been manageable, this has been the longest year. Constipation, lethargy and fatigue, edema, 2 bouts of neutropenia, capped off with vertigo lasting for over a month. His specialist believes the Venetoclax could be the root cause of the vertigo, but we wont know until the treatment is complete and since all of this is "manageable" no need to cut the treatment plan short. Its like having a migraine headache that never fully goes away for over a year. Its "manageable" but wears on both of us, like living in a labyrinth, not knowing what's going to happen next or when it will all end. I would love to hear and see confirmation of some really happy news. Thank you all again!

[Walkingtall62 in reply to lisakc1]

Hi, I am a headachy person and cannot imagine an migraine going in for a year, albeit manageable. Your hubby deserves the best for being able to put up with it, and you too. All the best. And here’s to the end of the treatment!

[Tonybdog]

I just started a few weeks ago. My doctor said he will check MRD it at 6 months. If peripheral blood is negative then they check by doing a bone marrow for MRD. I am not on a clinical trial.

[lisakc1 in reply to Tonybdog]

There has been no mention of testing for MRD throughout my husband's treatment... perhaps because insurance would not cover it as an essential test.

[Tonybdog in reply to lisakc1]

Yeah I’m not sure if insurance would cover it. I believe it is new for CLL patients to look at MRD and currently in research. I kind of got the impression he may extend the Venetoclex a little longer if I’m not so maybe if it guides treatment it could be justified?

[lisakc1 in reply to Tonybdog]

Or perhaps understand if the CLL has built up a resistance to the Venetoclax. Thank you!

[SofiaDeo in reply to Tonybdog]

MRD testing was paid for back in 2012 for me, using flow cytometry. Some insurances may not pay for the newer more expensive NGS one in the US, but most all pay for flow cytometry MRD ones. My Medicare plan paid for my NGS ones the past few years, Medicare approved it a few years ago.

[Tonybdog]

Good point!

[Teemed]

I’m on Calquence and after 1year my numbers look great. I asked my specialist at MD Anderson if I should test for uMRD snd he said it’s just chasing a number, it won’t change anything as my remission will be what it .

I broke out the champagne and streamers. We’ll celebrate every victory snd breather along the journey

[lisakc1]

Thank you! Congratulations! The champagne is on ice as we speak!

[DriedSeaweed]

My understanding is that the test needs to be done before and after treatment. It can’t be decided to do after a treatment.

Please correct me if I am wrong.

On the trial I am on I think they check a few times throughout. My next one is in 3 weeks. Almost half way done through treatment so I will try not to invest myself too emotionally into it.