For those who are interested in understanding MRD, the link below connects to some insight on MRD and testing from the NIH Library of Medicine.
The publication might be a bit more extensive than what the average CLL patients is looking to read, However, the high points can easily be retained, as the material is written clear and concise.
Thank you so much
Mrd/Umrd negative is certainly a promising measure, yet, t is not a guarantee. We still need the "cure".
This paragraph caught my attention:
An intensive treatment regime consisting of ibrutinib, fludarabine, cyclophosphamide and obinutuzumab (iFCG) has recently yielded a BM uMRD rate of 90% (FCM, ITT-based: 88%) after only 3 months of treatment in a cohort of IGHV mutated patients.
90% is impressive considering the other results.
healthunlocked.com/cllsuppo...
Impressive 5 year OS of 97.8 though all patients have the favourable mutated ighv.
Yes, they were relatively young and fit with low risk cytogenetics and mutated IGHV - the ideal patient group to withstand and benefit from chemo. Seems to me the concept was a power-packed, shock therapy designed to induce deep remissions, of short enough duration to avoid inflicting long-term damage to bone marrow function. Time will tell.
Thank you for the archive post from 1 year ago bennevisplace.👍
thank you for highlighting this article, I learned a lot from it and will now be asking about MRD testing at 6 months of my I&V treatment.
Publications from the NIH such as these can be a great source for the substabtiation of Hope. I love what Andrew Schorr of Patient Power always says "Knowledge can be the Best Medicine".
Knowing MRD status at 6 months of 15 cycle treatment isn't important. No trial of V+I stopped taking the full 15 cycles based on MRD and neither will you. It's far more important just before the end. Then if uMRD4 hasn't been reached Ibrutinib can be continued as monotherapy without a break.
I can't find CAPIVATE MRD results for those that had dMRD (detectable) and continued treatment. Those that reached uMRD4 had good results with 100% PFS for those that received Ibrutinib follow on and 95% PFS for placebo, that was reported as no statistical difference. The plot is from is CAPTIVATE FD and shows a shorter time to progression for dMRD.
pharmacyclicsmedinfo.com/do...
The FLAIR trial used MRD to guide stopping. They started testing at one year and then every 6 months. The stop time was set to twice the time taken to reach uMRD4. If uMRD4 was at 1 year the drugs were taken for 2years, 18 months to uMRD4 - 3 years of drugs, 2 years - 4 years of drugs.
Wow, really knowledgeable and very helpful reply, thank you so much.
You are right. From Peter Hillmen ASH abstract:
PB MRD was assessed at 12 mo and then 6 monthly and if negative, was repeated at 3 mo and 6 mo in PB and BM. If all were MRD neg, then the duration of I+V was double the time between start of I+V and the initial MRD neg PB (I+V duration: 2 to 6 years).
ash.confex.com/ash/2023/web...
Encouragement for those with unmutated IGHV, extract from healthunlocked.com/cllsuppo...
In this UK FLAIR trial, MRD-guided ibrutinib–venetoclax, including individualized treatment duration beyond undetectable MRD, resulted in significant improvement in progression-free survival and an apparent benefit with respect to overall survival among patients with previously untreated CLL.
The positive outcome in this arm of the FLAIR trial appeared most marked in patients with IGHV-unmutated CLL, with substantial improvements in progression-free and overall survival.
N.B. words in bold are mine.
Thanks again, I would have missed a great post from Jackie.
Thanks for the info Smakwater. I'm going to share this with my CLL team at NY Presbyterian when I see them next month. I'm on Venetoclax monotherapy till Sept 2024. At that point, we'll re-evaluate the need for therapy. My scientific 'gut feeling' tells me, I may achieve uMRD but it also tells me the uMRD won't last long.
Even if uMrd does not guarantee durability, it is a good measure of efficacy. I hope your treatment is durable.
Excellent article! Thanks for sharing!
An interesting and relatively easy article to understand but it highlights the complexity of the disease and how much more there is to understand about minimal residual disease results, what they mean and how best to use them. I’m presently waiting on my uMRD testing results of the PB and after reading this article I understand if I achieve uMRD in the blood it won’t mean too much especially in my case as my disease loves my marrow and there is always the lymph nodes to worry about. On the other hand, if I still have residual disease in the blood that won’t be good.
Thanks for posting this informative article.
Mark
For those whose eyes glaze over when reading papers there is also this video from the same year it was published (2019). Only a few hundred people have watched it so far so I am sure there are plenty of people here who haven’t seen it yet.
If you tune in to 2:33:35 Dr. Adrian Wiestner talks about MRD.
I sometimes forget the numbers we are dealing with. Dr. Wiestner reminds us that “at the time a typical CLL patient would start treatment there are trillions of CLL cells in the body. … So once you have effective treatment you reduce that by 99% so that gets us to complete remission. So by typical clinical tools we do not see CLL. Not on physical exam or routine blood work. ….(just watch it for more detail)…
[if uMRD achieved]
… “how many CLL cells are in the body we still have millions probably hundreds of million of [CLL] cells present at the time we call MRD negative.”
This was a pleasant event, Patient and Caregiver Educational Forum, I had the pleasure of attending. Watch in full to see presentations by Dr. Inhye Ahn (now at DFCI), Dr. Clare Sun (NHLBI), Dr. Brian Koffman (CLL Society), and Dr. Adrian Wiestner (NHLBI).
Good Point.
It is my understanding that currently standard MRD negative observation is done mostly by flow test and reveals less than 1:10,000? Anything that observes uMrd deeper than 1:10,000 requires next generation sequencing.
Thanks for the video, it looks interesting and very extensive. I will go back and watch it to the end as time allows.
MRD on venetoclax and ibrutinib 
Swimming, joy and sadness and MRD negativity
Good end to a bad year... My MRD Results are in!
