MRD on venetoclax and ibrutinib

[Hippo68]

I have been on this Trial for 12 months,I was told my Blood showed MRD Negative at my last hospital visit,but was called today informing me that it now shows MRD .002.Which means I cannot yet have my Bone Marrow checked until it shows Negative for consecutive hospital visits.I am not sure if this is a good thing,going from Negative to .002 in my bloods.Has anyone out there gone through the same thing.Many thanks for any replies as I cannot find anything online about this.

[Hidden]

blood tests are not infallible. Most likely you were not really mrd negative the last blood test. Extremley tiny amounts are hard to detect-one way or another

[Hippo68 in reply to Hidden]

Thank you for your quick reply,is .002 a good response and does it mean It will be MRD later on in my trial.

[Hippo68 in reply to Hippo68]

Meant to say MRD negative

[fell]

Hi Hippo,

I wonder if you were at 00.2 to begin with but the sample that they took for your first BMB didn’t show any cll cells in it. Totally theoretical - perhaps someone with more knowledge can weigh in?

Best,

Fell

[Hippo68 in reply to fell]

Thanks

[Hidden]

since the hospital rule is that -2 consecutive tests -must be negative- they must have a reason for the rule. Most likely what has happened to you has happened to others-ergo the rule.

[Hippo68 in reply to Hidden]

Thanks

[johnl]

I just got my 12 mo. V/I combo results and they also showed .002 down from .008 at 9mo. and .008 at 6mo. Like you, I don't know what to think. On the one hand it's a real good response, but on the other hand it hasn't really changed in 6 mo. I have a year left to go on the trial so I have a good chance of getting MRD negative since I'm only a rounding or sampling error away from it, but it looks like I may becoming resistant to the treatment. Anyway MRD is only a random number and it is what it is.

john

[Hippo68 in reply to johnl]

Like yourself I do not know if it is good news or not,as I have read that people go MRD negative after only 9 months which is good news.But I have been on the treatment for 12 months and it has taken time to get on to .002.Do not know,like your results,if it’s good news for a long remission time,once it goes negative.Will ask at next appointment in January,but would really like to know ASAP.

[avzuclav]

Here's a fascinating image that shows the dynamics of ALC / MRD while on I+V.

ascopubs.org/na101/home/lit...

For the full story, see this excellent paper from Dr. Hillmen and the CLARITY study of I+V:

ascopubs.org/doi/full/10.12...

[Hippo68 in reply to avzuclav]

Thanks for the info

[Newdawn Administrator]

Hi Hippo,

I think you’re doing pretty well actually and the variation you report is absolutely minute. This treatment is a slightly longer game and in the Clarity Trial, only 36% of I&V patients achieved MRD-U at 12 months;

‘In addition, 36% of patients achieved an MRD-negative remission after 12 months of combination therapy, which is rarely seen with ibrutinib monotherapy and occurs in a small proportion of patients treated with venetoclax.’

I’m on this treatment and my response at 6 months from the flow cytometry was not as good as yours but I’m still having a BMB at 9 months. Levels like .002 are so impressive and there’s still time to improve on this. It could be your bone marrow still had a ‘clear out to do’ after you achieved the negative result in your blood. This could perhaps have impacted in this marginal way on the peripheral blood test.

Stick with it you’re doing brilliantly!

Newdawn

[Hippo68 in reply to Newdawn]

Thanks and all the best with your treatment

[closh]

Hi Hippo

I got to MRD- (undetectable - blood and marrow) on I+V, then crept up to MRD- 0.01, then back to undetectable, then crept up and I think my last one was 0.09. These are all microscopic levels and from all of my normal blood tests, you can't see anything wrong.

MRD testing usually looks at a sample of 10,000 cells. At these low levels, there's no guarantee even with a couple of undetectable results that there aren't a few CLL cells hiding out somewhere.

Realistically, any low MRD levels are good and if you have a CLL cell doubling time of 6 months, for example, it'd still take quite a while for this to get up to problematic levels. The idea with I+V is that you then re-treat again and off you go for a few more years. Of course, some may be lucky to have all of their CLL cells killed or held off long enough so as to never need retreatment - it'll be a few years before data is in.

Graham

[Hippo68 in reply to closh]

Thanks Graham,for the information.

[Jonboy64]

My trial is a year in and I've had bone marrow aspirations every 3 months since the start. Not sure why they don't check your marrow, b/c that's what the venetoclax is supposed to target? I've been MRD negative in my marrow for 6months now. Best of luck to you.

[Hippo68 in reply to Jonboy64]

Sorry Jonboy sent the reply to myself in error.

[Hippo68]

Had my marrow checked about 6 months ago,showed MRD positive then,which was expected.I will only have marrow done again when consecutive bloods show MRD negative,next visit January if the bloods show negative,then another check done a month later.If both are negative then the bone marrow test.Hopefully all will be MRD negative by then and I can come off the drugs.

[Smakwater]

Hippo68,

If possible, what method is being used to qualify the counts, and where are the tests run (laboratory)?

JM

[Hippo68 in reply to Smakwater]

Not sure about the method they use,but the laboratory is in Leeds.I am on the Flair Trial.

[Smakwater in reply to Hippo68]

Just curious about the accuracy and precision of the protocol used for testing.

I was recently told that count used in my recent bone marrow biopsy was accurate to 1:100,000 or better.

[Hippo68]

I think it’s accurate to 1 in 10,000 cells in Bloods and Marrow.

[Canuck901]

What dose of I plus V are you still Taking now ?

[Hippo68 in reply to Canuck901]

420mg Ibrutinib and 400mg Venetoclax Daily

[Hippo68]

420mg Ibrutinib and 400mg Venetoclax Daily.

[Canuck901]

Wow does your body tolerate both those without any side effects ?

[Hippo68 in reply to Canuck901]

I was started on 420mg of Ibrutinib daily,to which I had several bad side effects,such as nausea,very upset stomach,mouth sores and just generally feeling unwell.These side effects lasted for about 6 weeks,then they slowly went away.After 2 months of taking Ibrutinib I was ramped up on a weekly basis with Venetoclax,100mg to start with then over 4 weeks onto 400 mg.Each ramping up session meant me staying overnight in the Hospital,just to make sure my body accepted the Drug.Once I was on the full dose for both Drugs I did once again have side effects,feeling unwell and with diarrhoea.But once again these faded over time,I can now take both Drugs Daily with no side effects.I can quite understand why some people drop out of the trial,as to start with it is hard to believe that your body will adapt to the Drugs.I must say though that all of the Doctors and Nursing Staff have been very good,and all the side effects were explained to me at the start of the trial,so I knew what to expect.I have been looked after very well and hopefully can now look forward to,at some stage,going MRD negative on Bloods and Marrow,and coming off of the Drugs for a while.

[Canuck901]

Wow that’s an incredible story. I heard ibruntnib has a lot more side effects than the. Venetoclax

[Hippo68 in reply to Canuck901]

Yes I found that to be true,but in my case maybe it’s because it was the first cancer killing drug to hit my body system.I cannot say that it is worse than Venetoclax,but I do know it effects everyone in different ways when first taken.You just have to hang in there to let your body accept it,it’s easy to say but just give it time.

[Canuck901]

What’s your age ? Thanks for sharing your journey. I hope the best for you.

[Hippo68 in reply to Canuck901]

I am 66 years old,but I am quite fit for my age,which helped when I started the treatment.When I felt ill when I started the treatment,I would go out for a fast walk and sometimes used the treadmill at home.This would help to make me feel better.

Than you Canuck for your posts.

[Canuck901 in reply to Hippo68]

That’s very good for you , most 66 yo are still healthy enough to handle these strong drugs. My father is in his mid 80: ,fairly healthy for his age but I’m concerned on what drugs he will able to tolerate when his treatment time comes

[Hippo68 in reply to Canuck901]

Yes I can understand your worries,but like I said before it’s bad to start off with,but if he has some help I am sure he will pull through.That is presuming they use drugs for his treatment,but I am sure the Hospital staff will help with what ever treatment he has to have.Good luck to you and your Father.

[Canuck901 in reply to Hippo68]

Thank so much, we have hope and love and support. Although it’s a bit scary I believe his best option will be Venetoclax