Thread by @Rfonsi1

So here is a thread on the use of MRD in MM. Before we start please know that I consult for Adaptive & are part of their Scientific Advisory Board. If you can get past this point thank you for coming. Prompted by @End_myeloma
#MMSM #ASCO19RF @mtmdphd @AdaptiveBiotech

MRD negativity is now shown to be highly prognostic in several studies. Furthermore, the HR effect is unprecedented, and far more powerful than any genetic marker. Particularly see French (IFM) study from 2018.
bloodjournal.org/content/early/…

Second point, IMHO, people are “dancing around” at the level of sensitivity, but to mee it appears that 10-6 should be the way to go. Some appease those who work with 10-5 but, truth be told, deeper is better.

Regardless of the method of detection, the deeper the better. Flow needs more cells to reach -6, but can be reported quickly. You can do NGS with far fewer cells but results take 2 weeks and we don’t always have original DNA ID. I do prefer, and use NGS

No one can contest the prognostic ability of NGS, but some will say “wait a minute” you are using an outcome as a prognostic variable? It’s all biology”. Both true. MRD is a landmark prognostic variable that will tell you who is likely at a much later time to do better. 1/2

So it clearly prognosticates. It’s true that biology influences who achieves MRD. But with the same biology you have widely different ranges of MRD negativity, according to treatment given. We could only imagine with MP or VAD to ever get to MRD negative. Treatment matters!

But the key question is: How will it change my practice? There are two ways it can change it today: prognostic conversation with patients. Second, consider treatment discontinuation (more on that below, I know controversial). Practice change is not synonymous with MD prescribing!

First I tell patients as soon as the results come back. If the get a 0 (zero) I even call them home - at night! It’s a big deal. It’s not synonymous with cure, but if you are tested you would much rather be MRD neg.
@sgiraltbmtdoc

Ok, but to change practice we will need Phase 3 trials. Really? What Phase 3 trials were needed to incorporate the free light chain into your practice? I could not imagine my practice without it now. Another test of great use. Why is MRD different? I stop therapy because of sFLC!

So here is how I stop Rx. In patients in long term CR, and on chronic therapy, it adds information on how to consider proceeding. Let’s start with maintenance. If you do Rev for how long?

Well we can argue for a long time about time limited maintenance or indefinitely, both are reasonable choices. So if you accept this, why could you not consider stopping Len in someone at 3 years in a CR with NGS MRD neg? It adds info for SDM. I tend to use Len indefinitely

Maybe a patient knowing it is still MRD positive, and on the fence about continuing therapy, because of some toxicity, may decide to go for longer. Maybe a patient with a sustained CR with MRD negative feels more.

It is not 100% determinant, but adds to the information we use in the clinic. So what are you waiting for? I do routinely at Day 100 and at least yearly in those in CR. Not hard to imagine a future where post SCT/Cart Rx treatment intensifies if MRD+ (adjuvant?)

In short I think MRD defines the two axis of mm Rx. The y axis of depth of response and the x axis for duration of therapy. I hope this was of help.

For a more detailed video see my interview with Lanny Kirsch from Adaptive

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