U-MRD6 is the new MRD-

[avzuclav]

U-MRD6 = Undetectable-Minimal Residual Disease (U-MRD6) (10-6 sensitivity)

Discussion

The majority of pts with BM U-MRD4 after first-line FCR were MRD6+ and these patients had shorter PFS; MRD analysis with a more sensitive assay may therefore more accurately assign prognosis. Not accounting for sensitivity, a higher proportion of BM than PBMC samples were MRD+. Plasma analysis was uninformative as all pts MRD+ in plasma were MRD+ in simultaneous BM or PBMC samples.

Defining prognostically-relevant thresholds for MRD using more sensitive methodology is important, particularly if U-MRD is used a surrogate for PFS in clinical trials or as an endpoint for treatment cessation. MRD6 may become increasingly relevant if venetoclax-based regimens and the addition of novel agents to chemoimmunotherapy achieve U-MRD6 in more patients than FCR. In this retrospective study, a number of samples did not achieve 10-6 sensitivity; optimization of sample collection is important to achieve 10-6 sensitivity in most pts. Finally, additional studies will be required to determine the risk for and kinetics of relapse in patients with low-level MRD6+.

ash.confex.com/ash/2018/web...

adaptivebiotech.com/clonose...

[Jm954 Administrator]

This is very interesting and thank you for posting avzuclav. Better MRD detection will allow us to determine which treatments are best. Looking at the data in the ASH reference I would like to see it broken down by genetics, mutation status, treatment type, first line or subsequent therapies. Then we might get somewhere in knowing what is really best for which type of CLL.

Jackie

[Cllcanada Top Poster CURE Hero]

Nice to see they are moving to deep waters... but the issue to my mind is achieving MRD to the 6th, not testing for it...

Deep NGS -MRD has been done in clinical trials for some time, but commercialization will help bring more mainstream, which is great.

Now we need 5 years of clinical trials...

~chris

[Jm954 Administrator in reply to Cllcanada]

I think we’ll only regularly get U-MRD6 when we can target treatments more exquisitely for each genetic subgroup.

Donating CLL cells for these longitudinal studies is so important and in the UK there is a UK Biobank which aims to provide cells to researchers for just this type of research. The data in this link is a bit out of date but gives you an idea. liverpool.ac.uk/media/livac...

[avzuclav]

In this video (mentioned by Chris) at ~4:45, Dr. Furman mentions U-MRD8 might be the equivalent of cure.

youtube.com/watch?v=WOfqcH9...(Not working as expected?)

I really hope the CLL community can standardize on the new definitions (or come up with better ones) since MRD- is a vague double negative.

At least call it UMRD-6 instead of U-MRD6!